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?
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:
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]