Sjogren's Quarterly: Why Language Matters

 I enjoy all of the Sjogren's Syndrome Foundation's publications. The most recent edition of Sjogren's Quarterly, The Professionals' Resource on Sjogren's lead article was entitled "Why Language Matters" and written by Florian Kollert, MD and Benjamin A. Fisher, MD. It was a very interesting read in which the authors voiced their concerns over the use of 'primary' and 'secondary' terms to classify Sjogren's Syndrome. Here's an excerpt: 

Historically, Sjogren's has been classified into 'primary' and 'secondary' disease. 'Primary Sjogren's is defined as a standalone entity occurring in the absence of another systematic autoimmune disease, whereas 'secondary' disease is associated with the presence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis (SSc), for example. Notably, the presence of a coexistent autoimmune disease is very common in Sjogren's (approximately 30% overall) when organ specific autoimmunity is also included.

In our recently published article (Kollert & Fisher, Rheumatology) we reviewed the historical justification for the distinction of 'primary' and 'secondary' Sjogren's based on genetics, clinical presentation, chronology, histology and serology, and found it difficult to justify the dichotomy based on existing evidence. We therefore recommend further research, and advocate abandoning the term 'secondary' unless strong evidence emerges of a pathological difference between these subsets. We further argue for a nomenclature including the associated disease (Sjogren's in association with...) to not only emphasize the second autoimmune disease but also Sjogren's itself. In our perspective, Sjogren's is an under-researched disorder, a situation that is even worse for patients with so called 'secondary' disease. This stands in sharp contrast to the potential impact of Sjogren's on quality of life, even when compared to other systemic  rheumatological disorders..............

.........Patients with 'secondary' Sjogren's are often excluded from clinical trials and were not incorporated in the development of the most recent classification criteria for Sjogren's. They were considered in the widely used 2002 criteria but neither histopathology nor autoantibodies were necessary for classification as 'secondary' Sjogren's. Thus, recent clinical trials investigating new compounds for patients with Sjogren's typically recruit patients with primary Sjogren's only. So it seems unclear if a drug which is eventually proven to have efficacy for these 'primary' Sjogren's patients; will be accessible to patients with 'secondary' disease also. Conversely, studies of other systemic autoimmune diseases such as lupus or rheumatoid arthritis have typically not excluded patients with concomitant Sjogren's. This provides a largely unexplored opportunity to derive additional early signals of potential efficacy in Sjogren's.......

.......Taken together, as there is currently no evidence for a major difference between the phenotype of 'secondary' and 'primary' Sjogren's we argue in favor of using the same set of classification criteria for both. Moreover, we take the side of abandoning the term 'secondary' in favor of 'Sjogren's in association with' to emphasize not only Sjogren's but also the associated autoimmune disease. The overlap between different systemic autoimmune diseases should be regarded as an opportunity to foster drug development and to further stratify our available treatment modalities and personalize our therapies. 

Well said. I agree on all points. 

Has your rheumatologist diagnosed you with 'secondary' Sjogren's syndrome? Has your care been affected as a result? 

One of the Good Guys

Here's some good news for your Saturday:

Sean Parker donates $10M for autoimmune research

Jon Swartz, USA TODAY 

SAN FRANCISCO — Taking a page from the philanthropic playbook of Facebook CEO Mark Zuckerberg, Sean Parker on Monday made a major gift of his own.

He donated $10 million to establish a new research laboratory at the University of California-San Francisco Diabetes Center for autoimmunity research — and strongly hinted more is to come.

The 35-year-old Parker, who is worth an estimated $3.1 billion, has an "ongoing interest in immunology," dating to his health issues with allergies and asthma.

"The strategic plan is to eliminate type 1 diabetes," he said. "By no means is this the last grant."

Parker, who started companies including Napster and Airtime and was Facebook's first president, said he hopes to be a "catalyst" for scientific research that leads to improved treatments and reduced costs. Continue reading here.

Autoimmune Disease: The Common Threads AARDA Conference Topic

I promised that I would share some of the goodness from last Saturday's Autoimmune Disease conference sponsored by the AARDA, National Psoriasis Foundation, and OHSU, and here's a sample.

I was impressed in particular with this speaker: Dr. Noel R. Rose, Director, Center for Autoimmune Research at Johns Hopkins University.

Dr. Rose's discussion examined the far-reaching effects of autoimmune disease on several populations, affecting far more people than I had imagined:

And it's an expensive disease in more ways than one:

I wish I would have taken a better picture of this excellent graph below, which dramatically illustrates the comparison of females to males in various autoimmune diseases. The picture is a bit blurry, so I will list the diseases from left to right. Keep in mind that the pink bar represents women and the blue men.
From the left:
Sjogren's Syndrome
SLE -- Systemic Lupus Erythematosis
Thyroid disease
Scleroderma
Myasthenia Gravis
Rheumatoid Arthritis
Multiple Sclerosis
Sarcoid
Ulcerative Colitis
Diabetes Mellitus

The next graph shows the incidence of autoimmune disease in the US back in 1995. These numbers have increased considerably and consistently since then:

In looking at our little Sjogren's blip on the graph above, I understood just a bit more why our disease is unknown to so many. Doesn't excuse it.....just explains it. We do make up a fairly small piece of the autoimmune pie.

Dr. Rose went on to explain that current theories about the development of autoimmunity are three-pronged:

He commented that in his opinion, even though there are three factors in the causation of AI, environmental factors are more than half the risk.

One of the environmental factors which is not listed on the above slide, is the proximity to the equator: if you live in a temperate climate, your chances of having an autoimmune disease is higher. If you live closer to the equator, the chances are less. In the picture below, the pink and cream areas represent a lower occurrence than do the grey and green. Interesting.

To summarize the development of autoimmune disease, Dr. Rose explained...

Which brought us to the topic of how we can prevent this train wreck:

Early intervention is important, but also a difficult issue to address, since appearance of many biomarkers which indicate development of the disease may precede the actual symptoms and diagnosis by many years, which frustrates both patients and the physicians attempting to diagnose and treat them.

The graph above shows the gradual increase in autoantibodies over several years before symptoms and diagnosis of SLE.

Biomarkers of early disease need to be identified much more quickly than at present, and additional and more specific biomarkers need to be identified, according to Dr. Rose.

New treatment modalities are generally focused on those drugs that can interrupt the immune chain of events. Various drugs target various players in this chain:

Notice that the rituximab target is listed as Anti-CD20, which is a surface antigen -- or specialized protein -- found on B lymphocyte blood cells. I've written previously about why B cells, antibodies, and antigens are important to sjoggies, read this and this.

So. To summarize:

Autoimmune disease is HUGE. There's lots of them -- at least 80, and they affect lots of people, women more than men.

While it is not known exactly what causes AD, the current theory is that a combination of heredity, hormones, and environmental factors are to blame; with environmental factors taking up more than their fair share. It is strongly suspected that seemingly unrelated diseases such as diabetes and heart disease AND Sjogren's syndrome may all be far more similar than had previously been thought in that their causes are autoimmune in nature.

The future of research and treatment of these diseases, which all may share similar etiology, hinges on the ability to identify these diseases much sooner than at present, since we now know that the immune system begins to develop autoimmune processes and cells long before some symptoms and thus, diagnosis, appear.

A better understanding of biochemicals and their tasks in the immune response is vital to developing medications that will block these specific problematic biochemicals.

I wish that Dr. Rose could have addressed us for at least another two hours, or two days. He has an enormous amount of experience working in this field of research. I would love to know more specifics about which of these biochemicals and thus biomarkers for disease are the latest and greatest targets of research.

Sjogren's Syndrome and B-cells

B-lymphocyte found here. Could this be the villain?  

I received a link from PubMed the other day leading me to an abstract of a study, which I found very intriguing. The complete study results have yet to be published, this is an Epub ahead of print. I'm looking forward to reading the study in it's entirety.

What caught my attention was the focus on B-lymphocytes in relation to Sjogren's syndrome disease activity.

Why?

Here's an extremely simplified answer to an extremely complex immune response: Current scientific thinking around Ss mechanism is based on the fact that, when studied under a microscope, moisture producing glands and cells are destroyed or altered in Sjogren's syndrome by infiltration of a subtype of a white blood cell: T-lymphocytes. So therapies were investigated which altered T cell activity in the hopes of stopping or diminishing T-lymphocytes' role in the cytokine/inflammatory cycle.

And. Those of us that have been around the autoimmune block a time or two know first hand that there has been very limited success in developing these therapies.

Recent studies, read this and this, indicate that although the current understanding of the T-lymphocyte's role in inflammation and cytokine cell destruction is accurate, there is ANOTHER specialized white blood cell which also may play an active role in this chain of autoimmunity: the B-lymphocyte.

Here's what researchers are hoping: that by inhibiting the B-lymphocyte, the self-destructive chain of events that lead to autoimmunity can be interrupted.

Study abstract found on PubMed, here:

B-cell populations and sub-populations in Sjögren's syndrome. AuthorsHamza N, et al. Journal Presse Med. 2012 Jul 26. [Epub ahead of print] Affiliation: University of Groningen, University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, 9700 RB Groningen, The Netherlands.

"Sjögren's Syndrome (SS) is a chronic inflammatory disorder affecting exocrine glands, in particular the lacrimal and salivary glands. The disease can be primary (pSS) or secondary to other systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and others. The systemic autoimmune character of pSS is also apparent from the occurrence of (non-organ specific) autoantibodies in this disease. Histopathologically, glandular involvement is characterized by focal accumulation of lymphocytes, particularly around epithelial ducts, with, sometimes, germinal center-like structures. The infiltrates largely consist of T-cells, with a preponderance of CD4-positive T-cells. As a result, the pathology in SS was primarily attributed to T cells. However, a break with the fixation on the role of T cells in pSS came when therapeutic B-cell depletion strategies proved remarkably efficacious in this disease, thereby indicating a major role for B-cells in the immunopathogenesis of pSS. In this regard, a closer look at the composition of B-cells and B-cell sub-populations, both in the peripheral blood and in target tissues, is worthwhile. In this review, we discuss current data on B-cells in pSS. B-cell depletion offers a unique possibility to study the recurrence of (pathogenic) B-cells and their characteristics in pSS patients treated with rituximab. Data on B-cell sub-populations in the peripheral blood and B-cell repertoire in the target tissues following rituximab treatment are discussed as well. We also address their state of activation, repertoire, and relation to B-cell activating factor (BAFF)." (Bolding mine.)

Rituximab, also known as Rituxan. Sound familiar? Yes, this is indeed the drug that I refer to as "mousy". Since my initial infusion cycle last spring, I have noticed increased energy reserves, increased saliva production, and complete absence of the lesions from my subacute cutaneous lupus erythematosus.

Guys. This could be big. Stay tuned.

Sjogren's Syndrome Knowledge Base

The most recent issue of Sjogren's Quarterly included an article highlighting the formation of a new Sjogren's database:

by Sven-Ulrik Gorr, Seshagiri R. Nandula, and Trevor Wennblom, University of Minnesota; Sara Michie, Stanford University; Ammon B. Peck, University of Florida; Steve Horvath and David T.W. Wong, University of California at Los Angeles


A new database has just been launched to provide an easy-to-use and integrated Sjogren's Syndrome Knowledge Base (SSKB; http://sskb.umn.edu) is open for use by all researchers and the public at large and includes genes and proteins linked to Sjogren's. As founders of this tool, we hope and expect that it will have a profound impact on future research in this disease and ultimately stimulate the formulation and testing of new hypotheses and experimental approaches to investigations into Sjogren's. 
     Sjogren's syndrome and other autoimmune diseases are complex diseases that involve many events that lead to disease initiation and progression. In Sjogren's it is not clear how environmental triggering events combine with cellular and genetic factors to cause an immunologic attack on the salivary and tear glands that ultimately leads to the symptoms of dry mouth and dry eye. The observation that diagnosis often lags behind the onset of disease by a decade or more further complicates the understanding of disease initiation and progression. Thus, despite the substantial efforts by clinicians and researchers around the world, Sjogren's still presents many questions: how is the disease triggered, what is the contribution of genetic susceptibility, how can we improve diagnosis, and what is the optimal treatment for any individual patient? 

Excellent.

The Sjogren's Quarterly -- aimed at medical professionals and researchers -- is yet another amazing product of the Sjogren's Syndrome Foundation.

Go. Join. Add your support to this most desperately needed research.

Sjogren's Syndrome and MicroRNA

A recent study which looked at microRNAs, (small pieces of the genetic material RNA, which influences which and when genes are turned on or off) caught my attention when the results of the study included potential autoimmune diagnostic and treatment uses in the manipulation of these little bundles:

MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs about 21 nucleotides in length. miRNAs have been shown to regulate gene expression and thus influence a wide range of physiological and pathological processes.


Abnormal expression of miRNAs has been reported in autoimmune diseases, mainly in systemic lupus erythematosus and rheumatoid arthritis. miRNAs can be aberrantly expressed even in the different stages of disease progression, allowing miRNAs to be important biomarkers, to help understand the pathogenesis of the disease, and to monitor disease activity and effects of treatment. Different groups have demonstrated a link between miRNA expression and disease activity, as in the case of renal flares in lupus patients. Moreover, miRNAs are emerging as potential targets for new therapeutic strategies of autoimmune disorders. Taken together, recent data demonstrate that miRNAs can influence mechanisms involved in the pathogenesis, relapse, and specific organ involvement of autoimmune diseases. The ultimate goal is the identification of a miRNA target or targets that could be manipulated through specific therapies, aiming at activation or inhibition of specific miRNAs responsible for the development of disease.


It is now apparent that miRNAs can potentially regulate every aspect of cellular activity, from dierentiation and proliferation to apoptosis, and they can also modulate a large range of physiological and pathological processes.

The study focused on several autoimmune diseases including Sjogren's syndrome:

Michael and colleagues explored the presence of miRNAs in saliva exosomes isolated from parotid and submandibular glands of patients with SS.They have shown that miRNAs can be identified in saliva, which suggests it may be possible to obtain information from these target organs without the need for invasive methods, such as biopsies.

The study authors conclude:

...investigations have shown that miRNA-based gene therapies targeting dysregulated miRNAs have the potential to become therapeutic tools.

Interesting. Gene-based therapy in the treatment of autoimmune disease. I'm keeping an eye on this one.

Treatment Target? Yes!

Thanks to a tweet by rheumatologist Dr. Michiel Zandbelt, I read this from Oxford Journals Rheumatology:
Fatigue and depression predict physician visits and work disability in women with primary Sjögren’s syndrome: results from a cohort study by Gisela Westhoff, Thomas Dörner, and Angela Zink

Conclusion. In pSS, lack of stamina and/or depression cause a higher level of individual and societal burden than dry eyes and mouth. Fatigue and depression deserve more recognition as treatment targets in pSS.

The article was included in a themed issue on rheumatology and work, February 2012, although the original piece was written in 2011.

I've said repeatedly that even though my issues with Sjogren's related dryness are problematic, my biggest difficulty by far is the fatigue and lack of stamina that I experience almost every day. I could tote my eye drops to work with me. I could drink enormous volumes of water. I could slather on lotion every five minutes.

But.

There is nothing I can do at present to treat or erase the effects of my fatigue to the point where I could be reliably and consistently be physically able to work. And when my fatigue is at it's highest, my mental capability is at it's lowest, which only compounds the problem of being a good employee.

Currently, the most effective treatment of my fatigue is to simply become horizontal. For lengthy periods of time. Which decreases most employee's productivity significantly.

I would love to see fatigue and yes, depression, become important autoimmune disease "treatment targets".

Now. So get on it, people.

SSF Breakthrough Goal: Decrease Time To Diagnosis by Fifty Percent!

The January 2012 issue of The Moisture Seekers Newsletter published by the Sjogren's Syndrome Foundation contains the newest goal for the SSF: To shorten the time to diagnose Sjogren's by 50% in five years. Currently, the average time from symptoms to diagnosis for many sjoggies is five years - and many much longer.

Needless to day, this is an excellent goal. This from Steven Taylor, SSF CEO:

"We cannot sit on the sidelines and let these patients suffer any longer. That is why the SSF Board of Directors is taking action to ensure we do everything we can to increase awareness and to help those patients yet to be diagnosed." 

The Foundation plans to reach this goal by following three plans of action:

• Increasing public awareness
• Increasing involvement from our friends and partners
• Increasing education and awareness among healthcare professionals

One way that all sjoggies can do their part in helping the foundation reach this important goal is to join the Sjogren's Syndrome Foundation. Your membership will help fund research, patient and professional educational events and materials, and help to increase global awareness of this disease. And as a member, you will have access to this wealth of information AND receive the Moisture Seekers Newsletter delivered to your home. Members of the SSF who are interested and motivated to help tackle public awareness are encouraged to be part of the Awareness Ambassador program, which is an impressive plan that arms sjoggies with the training, support, and materials needed to contact the media, speak to physicians, and distribute information to clinics and offices.

This issue of the Moisture Seekers also includes a physician perspective from Nancy Carterton, MD, FACR, rheumatologist and co-author of the excellent book and Sjogren's syndrome resource A Body Out of Balance - Understanding and Treating Sjogren's Syndrome.

"Sjogren's patients should not have to suffer any longer from the lack of physician awareness and education. When I see someone who has not been able to obtain a diagnosis for a long time, I face a much tougher job helping that patient.........we as physicians suffer as well when we cannot diagnose a patient." 

Well said.

I wonder how many lives would have been extraordinarily different had a diagnosis been made and treatment begun two and one half years sooner than the typical five? How many symptoms and long term problems could have been avoided? How quality of life for those patients would have been changed?

Even if you choose not to become a member, the Sjogren's Syndrome Foundation website has great information and resources available to everyone, as well as a list of upcoming patient seminars and fundraising opportunities. I'm always intrigued when I see the Sip For Sjogren's - A Fine Water Tasting Event. What a great concept! Who needs a wine tasting evening? What fun to taste specialty waters bottled from all over the world, and support an amazing cause in the process. The SSF also organizes walking events titled Sjogren's Walkabouts:

It's more than a walk. The Sjögren’s Walkabout is a national awareness and fundraising event. 

The event focuses on increasing community awareness of Sjögren’s syndrome as well as promoting a healthy and active lifestyle. Participants raise funds to support research and education programs offered by the Sjögren’s Syndrome Foundation.  

Everyone is encouraged to participate whether you come to an event to walk or to meet other fellow Sjögren’s supporters and cheer on the participants. Your attendance is important to show that Sjögren’s affects many.  

Together we will conquer this disease.

Yessssssss!

More Autoimmune Research

I read this latest research update from the National Institutes of Health with great interest.

A recent study conducted by NIH/National Institute of Environmental Health Sciences/University of Florida Gainesville determined that an alarming 32 million Americans have autoantibodies that target their own tissues. The study is the first of it's kind in that it looked at a nationally representative sampling of people carrying a positive ANA.

Although positive ANA titers are common in autoimmune disease, the presence of autoantibodies alone does not indicate that the person will go on to develop autoimmune disease.

The study is important in that it will serve as a baseline for future research into the causes of autoimmune disease:

"Previous estimates of ANA prevalence have varied widely and were conducted in small studies not representative of the general population," said Frederick Miller, M.D., Ph.D., an author of the study and acting clinical director at NIEHS. "Having this large data set that is representative of the general U.S. population and includes nearly 5,000 individuals provides us with an accurate estimate of ANA and may allow new insights into the etiology of autoimmune diseases." The findings appear online in the Jan. 11 issue of the Journal Arthritis and Rheumatism.

The study reached these conclusions:

A multi-disciplinary team of researchers evaluated blood serum samples using a technique called immunofluorescence to detect ANA in 4,754 individuals from the 1994-2004 National Health and Nutrition Examination Survey (NHANES). The overall prevalence of ANA in the population was 13.8 percent, and was found to be modestly higher in African-Americans compared to whites. ANA generally increased with age and was higher in women than in men, with the female to male ratio peaking at 40-49 years of age and then declining in older age groups. 

"The peak of autoimmunity in females compared to males during the 40-49 age bracket is suggestive of the effects that the hormones estrogen and progesterone might be playing on the immune system," said Linda Birnbaum, Ph.D., director of NIEHS and an author on the paper. 

The paper also found that the prevalence of ANA was lower in overweight and obese individuals than persons of normal weight. "This finding is interesting and somewhat unexpected," said Edward Chan, Ph.D., an author on the study and professor of the Department of Oral Biology at the University of Florida. 

"It raises the likelihood that fat tissues can secrete proteins that inhibit parts of the immune system and prevent the development of autoantibodies, but we will need to do more research to understand the role that obesity might play in the development of autoimmune diseases," said Minoru Satoh, M.D., Ph.D., another author on the study and associate professor of rheumatology and clinical immunology at the University of Florida.

You can read the entire report here. Read more about the National Institutes of Health here, and the National Institute of Environmental Health Sciences here.

Another Research Center for Sjogren's Syndrome!

This very, very good news from Sjogren's Quarterly:

The Oklahoma Medical Research Foundation (OMRN) has received a five-year $7.8 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health. The funds will be used to create the Oklahoma Sjogren's Syndrome Center of Research Translation which will focus on developing new ways to diagnose and treat Sjogren's. The center will be headed by Sjogren's Syndrome Foundation Research Grantee Kathy Moser, PhD....................."IMRF is already a world leader in Sjogren's research, and this grant allows us to continue important work on finding the causes and potential treatments for the disease," says Dr. Moser, who serves as primary investigator on the grant and director of the OMRF Sjogren's Research Center. "We'll be using new technology to make inroads on questions that have been asked about this disease for decades." 

Will My Daughters Inherit My Autoimmune Disease?

Daughters Quotes | Forward this Picture

It seems to me that the Moisture Seekers Newsletter, published by the Sjogren's Syndrome Foundation, just keeps getting better and better. 

I just received the October 2011 edition in my mailbox, and this issue is packed with great information. I especially enjoy the Q and A sections since the questions are all very pertinent and the answers written by medical experts. You can receive the Moisture Seekers newsletter for free by becoming a member of the Sjogren's Syndrome Foundation, which is as easy as going to their website, here.

As the mom of two daughters, I read this particular question and answer with great interest:

Question: I understand that autoimmune diseases can occur in families and I am concerned that my daughters may develop Sjogren's or another autoimmune disease. What is the recommendation for testing for autoimmune diseases?

Answer: Nancy Carteron, MD, FACR: The second question is the easier to answer. NO routine screening is helpful for the "future, potential" risk of developing Sjogren's. The most helpful thing is to be familiar with the myriad of potential symptoms/signs of Sjogren's and related autoimmune diseases/disorders. If any concerning signs develop, then one can start the investigative process. As someone with Sjogren's, you probably have experienced that this is not often a simple, straightforward process. There is no reason to be over-worried, as it is not highly likely that your daughters would develop the same autoimmune process as you.

Yes, there is a genetic component for all autoimmune diseases. However, it is very dilute because multiple genes (polygenetic) are involved. Historically, the HLA-DR3 (histocompatability) type has had the tightest connection with Sjogren's. HLA-DQ1/DQ2 has some association with more severe Sjogren's. Also, genes are modified by the environment, medications, viruses, etc. thus adding even more complexity to the susceptibility of autoimmunity. This process currently is an active area for research and is referred to as "Epigenetics" (gene modification).

The strongest genetic association is actually just the increased risk of developing autoimmune reactions in general. If a family member has Sjogren's, then there is a ~ 30 - 35% chance of developing an autoimmune disorder (PMID (Pub Med) # 12453311). Furthermore, it is usually some other disease, not the same on the the family member has.

Worrying will not help or change anything for your daughters. We know stress (different for different people) can trigger the immune system in a way to start an autoimmune process or make it worse. This is a further reason to be informed but not worry about it.

Gynecology and Sjogren's Syndrome

Yep. I used the same picture yesterday. Read on to see why. 

I received an email from a reader after yesterday's post. Although she appreciated the information about new insurance options for those that have been denied coverage, what she really wanted to know was: Where can I get a copy of the article about gynecological aspects of Sjogren's syndrome shown in the picture?

The story can be found in the September 2011 issue of The Moisture Seekers, published by the Sjogren's Syndrome Foundation. Members of the SSF receive every issue. Joining is easy and can be done online.

The topic of gynecological aspects of Sjogren's is an important one, but one that is very poorly understood. Recently, the Johns Hopkins Jerome Greene Sjogren's Syndrome Center has established a clinic dedicated to the gynecological problems of women with Sjs. Here's a few excerpts from this excellent article, written by Thomas Grader-Beck, MD and Anne Burke, MD, MPH:

Vaginal dryness has long been recognized as a manifestation of SS. There are few studies that address this symptom, but they suggest that vaginal dryness is frequent among women with SS. About a third of pre-menopausal SS patients are affected by vaginal dryness; this increases to 75 percent in the postmenopausal period. While vaginal, oral, and ocular dryness may coexist in the same woman, their severity may not correlate. In many cases, the vaginal dryness may be more severe than oral or eye dryness. Vaginal dryness also may occur before the onset of oral and ocular dryness in women with SS. Vaginal dryness may help to identify Sjogren's patients who have the characteristic autoantibodies (anti-Ro/La) but lack eye and mouth symptoms. Along with vaginal dryness, patients frequently complain about itching (pruritus) that can be debilitating.
     Patients with Sjogren's syndrome have a high frequency of dyspareunia (pain during intercourse). In a study of premenopausal women, 40 percent with SS complained of dyspareunia in contrast to only 3% without SS. Postmenopausal women with SS also have a higher frequency of dyspareunia than their healthy counterparts. 

The article goes on to note that the mechanisms that cause vaginal dryness and the resulting problems are very poorly understood. Unlike the eyes and mouth, there are no glands which provide lubrication within the vaginal tissue itself.

Therapy is frustratingly limited to few treatments at this time, and include topical estrogens and vaginal moisturizers. Read this:

As of yet, there is no definitive treatment for the vaginal symptoms of SS. Since there is inflammation in vaginal tissues of women with vaginal sicca due to SS, the question arises whether women may benefit from anti-inflammatory therapy, in particular in the premenopausal period. There currently is no information available in this regard. 

The Johns Hopkins Jerome L. Greene Sjogren's Syndrome Center has initiated two studies to better understand this difficult issue. You can read more about the Johns Hopkins Center and it's ongoing studies here.

The Financial Burden of Autoimmune Disease

The American Autoimmune Related Diseases Association and the American Coalition of Patients Groups recently released a white paper which explores the fiscal impact of ADs on patients and U.S. healthcare spending - The Cost Burden of Autoimmune Disease: The Latest Front in the War on Healthcare Spending. Bolding and parenthetical statements mine. 

The summary states:

Autoimmune disease as a category affects 50 million Americans. It is one of the top ten causes of death in women under the age of 651, is the second highest cause of chronic illness, and is the top cause of morbidity in women in the United States. Additionally, autoimmune diseases have been reported to be on the rise in the U.S. and around the world, making this poorly understood category of disease a public health crisis at levels comparable to heart disease and cancer. Because of a severe lack of awareness amongst the general public and medical practitioners and unequal allocation of research funding and focus at the National Institutes of Health (NIH), plus a lack of coordinated care and standardized diagnostic tests, the associated cost of autoimmune diseases has become a significant portion of the rising cost of healthcare in the U.S. Addressing the pressing concerns surrounding autoimmune diseases should be a major priority of the United States Congress as a means of reducing healthcare spending while ensuring improved public health.

Of particular interest was data showing the annual indirect and direct cost of Sjögren’s syndrome and rheumatoid arthritis (RA) against a control group:

This data was published by the Sjögren’s Syndrome Foundation and was produced by two independent UK studies16. The studies found that indirect costs totaled $21,369 per patient per year. These included time lost from current work, inability to work at all, or to work full-time, as well as costs associated with the necessity to hire outside help within the home to assist with tasks no longer possible due to disease progression, such as housework and yard work. With four million patients suffering from Sjögren’s syndrome in the U.S. today, this adds billions more to the already staggering financial burden faced by patients, your constituents, in the U.S. today.

According to the paper's authors, much of the blame of the staggering cost of autoimmune disease is placed squarely on the current health care provider system:

Innate problems exist for autoimmune patients regarding getting a diagnosis and onset of treatment which add unnecessarily to the cost of having these illnesses. According to an AARDA study, on average patients spend upwards of four years seeking an effective diagnosis. Visits to more than four physicians are typically needed; and because of poor physician training and education in this category, the AARDA study found that 46 percent of patients were told that they are constant complainers or too concerned with their health. The cost ramification of this is that the illness continues to progress throughout this process, extending the time to which patients begin to obtain proper treatment and care for their illness. Disease progression, unchecked with treatment, has major consequences, such as organ damage and physical disability that often lead to earnings losses and financial distress due to high out-of-pocket costs. Ultimately, after becoming unable to work and support themselves and their families, patients are forced to apply and obtain disability payments.

The paper went on to address ways in which our current health care system could be adapted to ensure better care for AI patients and in doing so, reduce the cost burden of these diseases to both patients and the current health care system providers:

• Streamlining the diagnostic process. 
• Coordinated care through community-based triage center. I was intrigued by their suggestion to create a new physician specialty - the autoimmunologist. This new specialist would serve as the head of a multi-disciplinary team of physicians within autoimmune triage centers, providing not only more cost-effective care but also increasing the quality of care for these patients. 
• Focus on research funding: knowledge limits waste. "Ultimately, better autoimmune disease costs and epidemiological studies are necessary to improve assessment of the prevalence of all 100+ autoimmune diseases so that the U.S. can allocate, in fairness, resources in funds for research and drug development, focus on research and medical training, and provide accurate information for developing public health policy."
• Increasing awareness. "....adding to a severe awareness gap are physicians. Many are poorly trained in this area and typically do not ask about a family history of autoimmune diseases on patient intake forms. It has been scientifically proven that these diseases are genetically linked; therefore, family history plays a major role. If the patient doesn’t know to tell the physician of a family history of autoimmune disease and the physician doesn’t know to ask, patients are destined for years of misdiagnosis or no diagnosis; and billions of dollars are spent that could have been saved with an increase in awareness."

The authors conclude:

Autoimmune diseases will continue to be a mounting public health concern in the U.S. and around the world for the foreseeable future. The cost associated with these diseases, while difficult to pin down accurately for all 100+ diseases, has clearly been illustrated to be a major component in the healthcare spending picture, adding perhaps hundreds of billions of dollars to healthcare spending through cost to individual patients and Medicare/Medicaid, as well as loss of productivity in the U.S. workforce. It is imperative that autoimmune diseases become a public health priority that is recognized throughout NIH institutes as well as amongst the congressional representatives who must represent the pressing needs of this growing constituency of Americans who live with autoimmune diseases.

Amen! Take the time to read this excellent white paper. 

T-Cell Research

Awesome T cell image found here. 

Medical News Today recently published this very encouraging article regarding a study that examines cellular defects in autoimmune diseases and cancer: 

"For decades, autoimmune diseases have been treated by reducing overall immune response. That's been effective in extending life spans, but has been hard on the quality of life for many of those patients," said Hong Jiang, M.D. Ph.D., a faculty member of the Division of Rheumatology, in the Department of Medicine at Columbia University Medical Center, and the leading scientist of the study and corresponding author of the paper. "Now that we understand the specific mechanism of how regulatory T cells discriminate between 'self' and 'non-self,' and the cellular/molecular defect that makes that process go awry, we hope to develop new type of therapies that specifically target the defect in patients without damaging their normal immune functions." 

.........Current therapies for treating autoimmune disease and controlling rejection of transplants result in nonspecific suppression of normal function of the immune system. In contrast to these existing approaches (which systemically suppress the immune system), therapies based on this new research are designed to selectively suppress immune responses to self-antigens without damaging the body's normal anti-infection and anti-tumor responses.

You can read more about this exciting study here. 

It's wonderful to see these important studies being conducted into the mechanism of autoimmune disease. It seems as though the hitch in this giddyup unfortunately comes in when scientists take this information to try to "develop those new types of therapies that specifically target the defect in patients without damaging their normal immune functions". 

A tall order, indeed. Go get 'em, Dr. Jaing. 

Another Reason to Support the Sjogren's Syndrome Foundation

I recently received this from the Sjogren's Syndrome Foundation:

Medical or other graduate students in clinical and/or scientific research with a focus on Rheumatology are invited to apply for a Student Fellowship in Sjögren's. The award will be made  through the ACR Research Education Foundation (REF) Preceptorship Program and is supported by the Sjögren's Syndrome Foundation.

Applications for projects in Sjögren's may be uploaded to the ACR website between now and August 2, 2010, with the award to be given October 1, 2010. One SSF-sponsored award will be granted through the ACR REF program in 2010. The SSF will appoint a Sjögren's expert to join the ACR research review team in deciding on the 2010 recipient.

Projects must be completed in an 8-week program during one academic year. The award either will be made through the ACR REF/Abbott Medical Student Research Preceptorship or the ACR REF/Abbott Health Professional Graduate Student Research Preceptorship. For more information, visit the REF websites listed below:

ACR REF/Abbott Graduate Student Research Preceptorship

(for medical and/or graduate students) 

http://www.rheumatology.org/ref/awards/hpprecep.asp

ACR REF/Abbott Medical Student Research Preceptorship http://www.rheumatology.org/ref/awards/summerresearch.asp

If you have any questions about the SSF Research Program, please contact us at: 

Email: research@sjogrens.org

Telephone: 1-800-475-6473, extension 215

www.sjogrens.org/research

Sincerely,

Sjögren's Syndrome Foundation

Here's evidence of your donation dollars hard at work in the SSF to help educate new researchers in Sjogren's Syndrome and other rheumatological disorders. Can't think of a better way to spend the money.

New Medications on the Autoimmune Horizon

Photo mine. 

On June 1st, I posted a blurb entitled Hope For New Treatment, which references a recent article from SELF magazine. The SELF article mentioned the use of three medications with potential for treatment of autoimmune disease: Estriol, Larazotide, and Benlysta. 

I thought it might be interesting to take a closer look at each of these medications. Here's what I found:

Estriol - trade name Trimesta - is a weak estrogen-producing molecule produced in the placenta of pregnant women. Without estriol, a pregnant woman's body would consider the fetus as "non-self" and produce antibodies to attack it. Or, in research terms, estriol offers immunologic privilege to the fetus. Interestingly, when estriol is being produced during the pregnancy of a woman with multiple sclerosis, not only does estriol protect the developing fetus, but the MS seems to move into a remissive state. Researchers theorized that administering estriol as a therapeutic drug could re-create this remission and decrease the development of the nervous system lesions produced in all MS patients. You can read more about estriol and it's potential for use in MS here. Trimesta's manufacturer is currently enrolling patients in phase II/III clinical trials. 

Larazotide Acetate has potential for reducing the effects of celiac disease, an autoimmune condition that attacks the intestines in response to the ingestion of wheat and gluten. People with celiac disease have been found to have elevated amounts of a specific protein - zonulin - in their gut. Zonulin, discovered by University of Maryland researcher Alessia Fasano, is believed to have the ability to "unlock" the barrier cells lining the intestines, lungs, and the brain to allow large molecules such as gluten to leave the intestines, causing disease. My explanation is does not do justice to this incredibly complex process, but you can read a more detailed explanation of celiac disease and zonulin in the article entitled Eating Away at You. Which brings us, finally, to the drug Larazotide, which blocks the zonulin receptor cells in the intestine and shows promise in the early stages of human trials. 

Benlysta (belimumbab) is a medication which is being developed for use in SLE, or lupus. Here is the manufacturer's description of it's actions:

BENLYSTA inhibits the biological activity of B-lymphocyte stimulator, or BLyS. BLyS is a naturally occurring protein discovered by HGS [7-8], which is required for the survival and development of B-lymphocyte cells into mature plasma B cells. Plasma B cells produce antibodies, the body’s first line of defense against infection. In lupus and certain other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production of autoantibodies – antibodies that attack and destroy the body’s own healthy tissues. The results of prospective observational studies show a significant correlation of elevated levels of BLyS with SLE disease activity. BENLYSTA acts by: (1) specifically recognizing and binding to BLyS, (2) inhibiting BLyS’s stimulation of B-cell development, and (3) restoring the potential for autoantibody-producing B cells to undergo the normal process of apoptosis (programmed cell death). Preclinical and clinical studies show that BLyS antagonists such as BENLYSTA can reduce autoantibody levels in SLE.  

Benlysta showed enormous potential in the early stages of clinical trials, but at week 76, although showing a higher response rate than placebo, the difference between Benlysta treated patients and placebo patients was less than expected, implying that the effects of the drug may wane before 76 weeks of use. In a 4/21/10 press release from the Alliance for Lupus Research, this slightly disappointing data was delicately phrased as the "secondary endpoint did not reach statistical significance". 

Although these drugs are not available in the US at this point, they all show promise. And what's even more important - their development is proof of ongoing, significant research in the understanding and treatment of autoimmune disease. 

New Autoimmunity Medical Journal

It's indisputable: autoimmune disease desperately needs more research, and more awareness within both the healthcare practitioner and public arena. So the announcement yesterday of the launch of a new publication entitled Autoimmunity Highlights is good news. This from Medical News Today:
Springer is launching a new journal Autoimmunity Highlights, an independent, international, peer-reviewed journal that publishes papers related to the diverse aspects of autoimmunity, and seeks to be a bridge between the clinic, the laboratory and the specialists who are involved in the complex world of autoimmunity diagnosis. The journal focuses on pathogenesis, immunology, genetics, molecular biology, diagnostic auto-antibody tests, epidemiology, pathophysiology and the treatment of autoimmune diseases.......Springer Executive Editor of Medicine Journals in Italy, Carlotta d'Imporzano, said, "Autoimmune diseases can affect any part of the body, and have clinical manifestations that make diagnosis an extremely difficult task. Because this discipline is rapidly growing in relevance, this is the perfect time for the launch of the new journal Autoimmunity Highlights." 

Image found here. 

Walkabout For Sjogren's Syndrome

Jennifer Pettit, over at Understanding Invisible Illness has written a couple of spirited posts about an upcoming fundraiser for the Sjogren's Syndrome Foundation in Philadelphia on May 1st. She is quickly becoming an enthusiastic advocate for those of us with invisible illness in her work, in her faith community, and in her daily life.

If you don't already donate to the Sjogren's Syndrome Foundation, you may want to consider sponsoring Jen as she participates in the 2010 Philadelphia Tri-State Sjogren's Syndrome Walkabout. You can read more about her participation here.

You go, girl!

Research for autoimmune diseases is desperately needed and greatly underfunded. Monies collected from this walkabout and other fundraising efforts by the Sjogren's Syndrome Foundation help support research and awareness campaigns.

Image by aldin

Grand Challenges in Global Health

I'm a Bill fan. No, not the Kill Bill movies (eww), or Bronco Bill.

I'm a Bill Gates fan, more specifically the Bill and Melinda Gates Foundation fan. To be honest, I don't have a PC. My trusty laptop is an Apple.....but most Pacific Northwesterners like myself take some pride in the fact that Bill and his little company, Microsoft, started right here in our neck of the woods. And what a company. I am completely incapable of entering the PC vs Apple technical discussion, but what I am impressed with is what Bill has done with the immense fortune that he has amassed as a result of his ingenuity.

I agree completely with the Gates Foundation's mission: that all lives have equal value. The Foundation goes on to further elaborate on it's mission as defined in it's guiding principles.Their principles can be found on the Foundation's website:

The 15 principles below reflect the Gates family's beliefs about the role of philanthropy and the impact they want this foundation to have. The principles guide what we do, why we do it, and how we do it. While many of them are fundamental to the way we operate, we will remain open to amending them as we grow and learn more about our work.

Guiding Principle #1: This is a family foundation driven by the interests and passions of the Gates family.

Guiding Principle #2: Philanthropy plays an important but limited role.

Guiding Principle #3: Science and technology have great potential to improve lives around the world.

Guiding Principle #4: We are funders and shapers—we rely on others to act and implement.

Guiding Principle #5: Our focus is clear—and limited—and prioritizes some of the most neglected issues.

Guiding Principle #6: We identify a specific point of intervention and apply our efforts against a theory of change.

Guiding Principle #7: We take risks, make big bets, and move with urgency. We are in it for the long haul.

Guiding Principle #8: We advocate—vigorously but responsibly—in our areas of focus.

Guiding Principle #9: We must be humble and mindful in our actions and words. We seek and heed the counsel of outside voices.

Guiding Principle #10: We treat our grantees as valued partners, and we treat the ultimate beneficiaries of our work with respect.

Guiding Principle #11: Delivering results with the resources we have been given is of the utmost importance—and we seek and share information about those results.

Guiding Principle #12: We demand ethical behavior of ourselves.

Guiding Principle #13: We treat each other as valued colleagues.

Guiding Principle #14: Meeting our mission—to increase opportunity and equity for those most in need—requires great stewardship of the money we have available.

Guiding Principle #15: We leave room for growth and change.

Recently, the Gates Foundation announced its recipients of Grand Challenges in Global Health grants:

ARUSHA, Tanzania – The Bill & Melinda Gates Foundation today announced 76 grants of US$100,000 each to pursue bold ideas for transforming health in developing countries.  The grants support researchers in 16 countries with ideas as diverse as a developing an electronic nose to diagnose tuberculosis and using chocolate to help prevent malaria.

I'm posting just a few of the innovative health projects that were awarded funding. You can see them all here.

o   Andrew Fung of University of California, Los Angeles aims to develop chewing gum that can detect malaria biomarkers in saliva;

o   Ranjan Nanda of the International Centre for Genetic Engineering & Biotechnology in India will attempt to create a handheld “electronic nose” that gathers and analyzes breath samples to diagnose tuberculosis;

o   Udantha Abeyratne of the University of Queensland in Australia will equip mobile phones and mp3 players with microphones to record cough and sleep sounds, which could then be screened to diagnose pneumonia.

o   Steven Maranz of Weill Cornell Medical College in New York will test the ability of a compound found in chocolate to keep malaria at bay.

Inspector Number Nine

Image found here.

Remember when your mom would buy your underpants in those plastic packages containing at least three pair? Or at Christmastime when your Aunt Zelda would give you the underwear jackpot - seven pairs of day of the week underwear? When you would rip open the package, a little tag would drop out. The tag was a small white slip of paper that simply said: inspected by number nine. Or seven, or twelve, or whatever.

And yes, to publicly admit my weirdness, as a child I used to envision a giant number nine critically examining underpants one by one all day long. He had long black plastic arms and Mickey Mouse style white gloves. He would snap that waistband and tug at the seams. Imperfect panties were tossed into a garbage bin, never to be seen again.

Come to think of it, as a child, Inspector Number Nine seemed huge and the underpants very small in my imagination. Now, as an adult, the imaginary underpants have gotten considerably larger, and good old Inspector Number Nine seems much smaller in comparison.

Hm. Not going there. Back to reality:

I thought about my Inspector when I read a summary of a recent study completed and published by the Oklahoma Medical Research Foundation. Their research found that even in healthy individuals, potential autoimmunity-inducing cells can be found:

As antibody-producing B cells develop in the bone marrow, the body tests them to determine whether their antigen receptors are apt to confuse self tissues for intruders. If so, their receptors are either rearranged to make new, non-autoreactive versions-a process called 'receptor editing'-or the cells are killed off while still in the bone marrow. Yet a minority manages to escape, slipping into the body as mature B cells with a propensity for self-attack.

What does this mean for autoimmune patients? Probably that a great deal more research is needed to explain why our bodies' testing mechanism allows far more flawed B cells to escape detection than those people without autoiummune disease.

Personally, I think that our bodies need Inspector Number Nine checking out those antigen receptors.