The molecular chaperone transthyretin (TTR) has been shown to be an antigenic target for B- and T-cell mediated autoimmune responses in juvenile idiopathic arthritis, according to researchers at Albert Einstein College of Medicine and the Children’s Hospital at Montefiore (CHAM). TTR is a chaperone responsible for vitamin A (retinol) and thyroxine transport. 

In this study, abnormal accumulations of proteins in both synovial fluid and blood of patients meeting the International League Against Rheumatism criteria for JIA were analyzed. They did not find TTR in any of the 26 control patients who did not have JIA; however, there were significant increases in levels of TTR in the 50 patients diagnosed with JIA.  Patients with JIA were noted to have unusually high levels of autoantibodies to TTR.

Additionally, 3 distinct HLA-DR1–restricted TTR peptides were found to induce CD4+ T cell expansion and increase interferon (IFN-)γ and tumor necrosis factor (TNF)-α production in 3 out of 17 analyzed patients.

Study author Laura Santambrogio, MD, PhD, professor of pathology, microbiology & immunology, and of orthopaedic surgery at Albert Einstein, told Clinical Pain Advisor that she and her colleagues hope that the findings of this report “will lead to a simple biomarker test, which would help clinicians better diagnose (JIA) and/or to categorize different stages of the disease.”


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“A larger cohort of patients needs to be analyzed, as well as patients with different subtypes of JIA and different stages of the disease, to help refine these initial findings,” Dr Santambrogio said.

The report was funded by grants from the National Institutes of Health (AG045223, AI38996, and AI48833, AR-47363, NIH AR-48929) and by the Cincinnati Children’s Research Foundation and the Cincinnati Genomic Control Cohort.

Summary and Clinical Applicability

This study found increases in TTR production and TTR autoantibodies in patients with JIA as compared to matched controls. The researchers state that their findings “provide evidence of a role for TTR as an autoantigen potentially involved in the pathogenesis of JIA and suggest a role for protein oxidation or other posttranslational modification in stimulating autoimmune responses targeting this protein”.

Reference

Clementi CC, Moncrieffe H, Lele A, Janow G, Becerra A, Bauli F, et al. Autoimmune Response to Transthyretin in Juvenile Idiopathic Arthritis. JCI Insight. 2016. doi: 10.1172/jci.insight.85633.

This article originally appeared on Clinical Pain Advisor