TRIM Autoantibodies Tied to Primary Sjögren Syndrome Disease Severity

Anti-tripartite motif (TRIM)38 autoantibodies were found to be associated with increased disease severity in primary Sjögren Syndrome (SS), according to research published in Arthritis & Rheumatology.¹ 

Sera from patients with primary SS, an autoimmune disease characterized by autoimmune glandular destruction and lymphocytic infiltrates of the lacrimal and exocrine salivary glands, have been shown to have detectable autoantibodies to several cellular proteins, especially Ro60/TROVE2, La/SSB, and Ro52/TRIM2.² Further, the autoantibody anti-Ro52 associated with primary SS belongs to a family of TRIM-containing proteins, which have been linked to salivary gland dysfunction.²

Nina Wolska, MSc, of the Oklahoma Medical Research Foundation in Oklahoma City, and colleagues sought to characterize another TRIM autoantibody, anti-TRIM38 to better understand its clinical relevance in primary SS. Serum samples were obtained from 235 people with primary SS and 50 controls. Using ³⁵S-methionine-labeled TRIM38 protein, the samples were analyzed in vitro for reactivity. Anti-TRIM38 autoantibodies were detected in 10.22% (n=24/235) of those with primary SS and 4% (n=2/50) of controls.

In study participants with primary SS, anti-TRIM38 positivity was associated with significantly lower Schirmer test score (P = .0003) and significantly higher ocular surface staining score or van Bijsterveld score (P <.0001), and focus scores ≥3 on minor labial salivary gland biopsy (75% vs. 46.5%; P =.0185).  

Further, the authors found a significant association between anti-TRIM38 positivity and the presence of anti-Ro52, anti-La, rheumatoid factor, anti-Ro60, and hypergammaglobulinemia. Finally, anti-TRIM38 antibodies reacted to 2 domains of TRIM38 that reacted with TRIM21 after affinity purification. 

”Anti-TRIM21 [antibodies] are common in [Sjogren syndrome], but this protein is a member of a large family of highly related proteins. [Therefore], we thought there might be antibodies to other members of the family,” noted co-study author Robert Scofield, MD, of the University of Oklahoma Health Sciences Center in Oklahoma City, in an email to Rheumatology Advisor.

Summary and Clinical Applicability

Autoimmune disease diagnosis, classification, and prognosis are dependent on diagnostic detection of autoreactive antibodies

In this study, sera from some patients diagnosed with primary SS tested positive for autoreactive anti-TRIM38 antibodies. An association was found between anti-TRIM38 antibody positivity and disease severity in patients with primary SS.  

Dr Scofield continued, “The diversity of the autoimmune response in Sjögren syndrome is far from completely described. New antibodies such as this one may have important clinical and pathophysiologic implications. In this case, anti-TRIM38 is associated with worse disease.”

“The present findings clearly establish that TRIM38 is a valid target for autoantibodies in primary SS. Additionally, [the results of the study] demonstrate an association between anti-TRIM38 positivity and greater disease severity in patients with the disorder.”

Study Limitations and Disclosures

It is unknown whether anti-TRIM38 antibodies lead to direct damage, but positivity for anti-TRIM38 antibodies was associated with more severe sialadenitis on focus score and measures of dry eye. It is also important to note that study did not find statistically significant differences in whole unstimulated saliva flow between those patients who were anti-TRIM38−positive and those who were anti-TRIM38−negative patients.

This study was funded by grants from the National Institutes of Health and the Oklahoma Medical Research Foundation. 

References

1. Wolska N, Rybakowska P, Rasmussen A, et al. Brief report: patients with primary Sjögren’s syndrome who are positive for autoantibodies to tripartite motif-containing protein 38 show greater disease severity. Arthritis Rheumatol. 2016;68(3):724-729.

2. Kyriakidis NC, Kapsogeorgou EK, Tzioufas AG. A comprehensive review of autoantibodies in primary Sjögren’s syndrome: clinical phenotypes and regulatory mechanisms. J Autoimmun. 2014;51:67-74.