Background Disruption of normal innate immune responses to pathogens and toxins may contribute to Rheumatoid Arthritis (RA) pathogenesis. The host defense peptide cathelicidin (LL37) is produced as part of the innate response to microbes and is increased in inflamed synovium early in disease (1). Vitamin D acting thru its nuclear receptor has innate immunologic activity that may lead to the production of host defense peptides in response to microbial triggers. Vitamin D receptor polymorphisms are associated with RA in some populations.
Objectives We sought to determine associations of serum LL37 with vitamin D, prior mucosal infections as assessed by immune responses to the common urinary pathogens E coli and proteus and evidence of periodontal disease, and clinical measures of disease activity in patients with recent onset inflammatory arthritis.
Methods Subjects (n=231) enrolled in a longitudinal early arthritis cohort had synovitis (>1 swollen joint) for less than 1 year. (mean age 47±14 years, 71% female, 55% met ACR criteria for RA, 45% ACPA +ve, 55% Rheumatoid Factor (RF) +ve, median swollen28 joints (3) and tender 28 joints (4), ESR (15), CRP (7). Clinical disease measures and smoking history (self-report and cotinine levels) were recorded. Baseline DMARD naïve serum was tested for LL37, serum 25OH-vitamin D, immune responses to common pathogens (Escherichia coli IgG and IgM, Proteus mirabilis IgG and IgM) and anti-cyclical citrullinated peptide2 (CCP2) by ELISA. HLA shared epitope and common vitamin D receptor polymorphisms (Fokl, Bsm1, Apa1) were detected by sequencing. A subset (n=26) were examined for periodontal disease (PD) using the periodontal screening record (PSR). Associations of LL37 in serum and saliva with clinical disease and other parameters were tested.
Results Serum LL37 levels were not associated with clinical disease activity, RA diagnosis or smoking status (ever/current smoking or cotinine levels). No correlations were seen between serum LL37 levels and titers of IgG or IgM antibodies directed to the common urinary pathogens Escherichia coli and Proteus mirabilis. LL37 was not associated with serum 25OH vitamin D levels or with vitamin D receptor polymorphisms. Serum LL37 levels were highest in ACPA +ve subjects (10 vs 14 p=0.003). This association was independent of shared epitope status, VitD Fokl polymorphisms, or smoking status. No subjects were periodontally healthy (edentulous n=3, gingivitis n=10, PD n=13). Median salivary LL37 levels were higher in subjects with PD compared to gingivitis (20 vs 9 p=0.03) but did not correlate with serum LL37 levels or arthritis activity.
Conclusions Cathelicidin expression is associated with ACPA positivity and periodontal disease although we did not see associations of cathelicidin with arthritis disease activity or prior bacterial infection. This supports the hypothesis of an association between periodontal infection and inflammatory arthritis and suggests a link with innate host responses that needs further evaluation.
Hoffman Ann Rheum Dis 2013;72:1239
Disclosure of Interest None declared
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