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The relationship between Sjögren’s syndrome and central nervous system disorders

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Summary

A recent study lead by Julius Birnbaum, M.D., M.H.S. and Livia Casciola-Rosen, Ph.D. in the Division of Rheumatology, explored the relationship between Sjögren’s syndrome (SS) and specific types of central nervous system disorders.  In these disorders, called demyelinating disorders,  the protective covering that surrounds nerve fibers is damaged, leading to a variety of neurological symptoms. Such disorders have been thought to be linked to SS, but this study shows that not all are direct neurological complications of SS. These findings help to identify the spectrum of neurological diseases that are directly attributable to SS.

Why was this study done?

Sjögren’s syndrome (SS) is a rheumatic disease that may include central nervous system (CNS) complications, including demyelinating diseases that can affect the brain and the spinal-cord. One such severe demyelinating disease is termed the “neuromyelitis optica spectrum of disorders (NMOSD),” and may rapidly cause blindness and paralysis. Although SS patients may experience NMOSD, it is uncertain whether this is because NMOSD is a direct CNS complication of SS, or whether NMOSD is a distinct autoimmune disease that develops coincidentally in some patients with SS. NMOSD is associated with a highly specific antibody biomarker, which targets the protein aquaporin-4 (AQP4). AQP4 is the primary water pump channel in the CNS that moves water in and out of cells. If antibodies to AQP4 are only seen in SS patients with NMOD, this would indicate a coincidental relationship. However, if antibodies to AQP4 are also seen more broadly in SS patients, even without CNS disease, this would indicate a causal relationship between SS and NMOSD.

How was this study done?

To further understand the relationship between NMOSD, other CNS demyelinating syndromes, and Sjogren’s syndrome, the authors compared the frequency of antibody biomarkers associated with SS and developed a test to detect antibodies to AQP4 in three disease subsets: Group 1 included 11  SS patients with NMOSD, Group 2 included 8 SS patients with demyelinating disorders other than NMOSD, and Group 3 included 90 SS patients without CNS demyelinating disorders.

What were the major findings?

Antibodies to AQP4 were seen in all 11 of the SS patients with NMOSD, but not in any of the 8 SS patients with other demyelinating syndromes, or any of the 90 SS patients without NMOSD. A new test to measure AQP4 antibodies termed a “fluorescence-activating cell sorting (FACS)” assay was developed. This test was able to detect AQP4 antibodies more frequently than the commercially available tests done at time of routine clinical care. The FACS assay was able to detect AQP4 antibodies even in patients with NMOSD treated with aggressive therapies that suppresses the immune system.

What is the impact of this work?

This study is the first example to use the detection of antibodies to AQP4 to understand the relationship between NMOSD and SS in a large number of well-characterized SS patients. The authors determined that NMOSD, as well as multiple-sclerosis-type demyelinating syndromes, are not direct complications of SS. Instead, the co-occurrence of NMOSD and SS reflects two disorders driven by intense, albeit unrelated autoimmune disorders. Therefore, if a SS patient is developing paralysis, blindness, and other complications of NMOSD, then emerging therapies which are strictly used to treat SS may not be effective treatment. In contrast, emerging therapies which are not typically used in SS, but may be efficacious for NMOSD, can be considered for patients with SS NMOSD.

This research was supported by:

The Rheumatic Disease Research Core Center at the Johns Hopkins Division of Rheumatology, the National Institutes of Health (P30-AR053503, DE-12354-15A1, and K23 AR064279 ), and the Jerome L. Greene Foundation.

Link to original research article:

The Relationship Between the Neuromyelitis Optica Spectrum Disorder and Sjögren’s Syndrome: Central Nervous System Extraglandular Disease or Unrelated, Co-occurring Autoimmunity?

Birnbaum J, Atri NM, Baer AN, Cimbro R, Montagne J, Casciola-Rosen L. Arthritis Care Res (Hoboken). 2016 Oct 1. doi: 10.1002/acr.23107. [Epub ahead of print]

Erika Darrah

Erika Darrah, Ph.D. is an Assistant Professor of Medicine in the Johns Hopkins University Division of Rheumatology with an interest understanding the mechanisms that drive the development of rheumatic diseases.

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