Do IgA antibodies to Chlamydia trachomatis have protective role in humoral immunity: a study in reactive arthritis patients.

Chlamydia trachomatis-induced genitourinary Reactive Arthritis (ReA) can serve as good model for host-pathogen interaction. However, due to poor antigen presentation, cell-mediated immunity does not contribute as anticipated. Present study aims to evaluate protective role of anti-C. trachomatis antibodies vis-a-vis inflammatory chlamydial Major Outer Membrane Protein (MOMP). Prospective study was undertaken in 30 patients with genitourinary ReA. 30 Rheumatoid Arthritis (RA) and 30 osteoarthritis patients constituted controls. Subjects found to be PCR-positive for C. trachomatis were investigated for presence of MOMP in Synovial Fluid (SF) by fluorescence assay while anti-C. trachomatis IgA/IgM antibodies were estimated in SF/venous blood by ELISA. C. trachomatis MOMP was evident by the presence of elementary bodies in SF of 9 ReA PCR-positive patients (30%; p < 0.05 versus controls). Local secretory IgA antibodies were detected in 12 (40%) patients with ReA (p < 0.0001 versus controls); among 12 patients with anti-chlamydial IgA antibodies, 9 showed the presence of both MOMP and IgA antibodies in SF. 58.3% ReA patients (7/12) with secretory IgA antibodies were also positive for circulatory IgA antibodies (p < 0.01 versus controls). Serum IgM antibodies were present in 4 ReA (13.3%) and in 1 RA (3.3%) patient, respectively. In conclusion, the present study suggests that in ReA patients with chronic, persistent C. trachomatis infection in synovium, the chlamydial MOMP is triggering factor for generating a protective immune response by inducing anti-C. trachomatis IgA antibodies in the SF of large number of patients.

Diagnosis of Chlamydia trachomatis in patients with reactive arthritis and undifferentiated spondyloarthropathy.

INTRODUCTION: There is a paucity of information on the frequency of Chlamydia trachomatis-induced reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) in India. In this study, arthritic patients suffering from ReA, uSpA, and rheumatoid arthritis (RA) were screened to investigate the presence of C. trachomatis infection in the synovial fluid (SF) or serum by molecular and non-molecular methods. METHODOLOGY: A total of 76 arthritic patients with ReA (n = 16) and uSpA (n = 22) composed the study group while those with RA (n = 38) served as controls. The detection of C. trachomatis DNA was done by semi-nested PCR (snPCR) and nested PCR (nPCR) targeting two different genes of C. trachomatis, namely major outer membrane protein and plasmid, respectively. The presence of serum or SF immunoglobulin IgG and IgA antibodies against C. trachomatis was studied by commercial enzyme-linked immunosorbent assay kits. RESULTS: The SF from 9 of 38 (23.6%) patients (5 with ReA and 4 with uSpA) was positive for at least one C. trachomatis DNA by snPCR or nPCR in comparison to RA (1/38 [2.6%]; p value < 0.05). There was no correlation between the snPCR or nPCR and the serological results of patients with ReA or uSpA. CONCLUSIONS: As molecular diagnostic techniques established intra-articular C. trachomatis infection among this group of seronegative spondyloarthropathies in India, these findings should be viewed with concern, and snPCR or nPCR should be considered for a more reliable diagnosis.

Identification of autoantibodies against transthyretin for the screening and diagnosis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic and inflammatory rheumatic disease that leads to inflammation of the joints and surrounding tissues. Identification of novel protein(s) associated with severity of RA is a prerequisite for better understanding of pathogenesis of this disease that may also have potential to serve as novel biomarkers in the diagnosis of RA. Present study was undertaken to compare the amount of autoantigens and autoantibodies in the plasma of RA patients in comparison to healthy controls. Plasma samples were collected from the patients suffering from RA, Osteoarthritis (OA), Systemic lupus erythematosus (SLE) and healthy volunteers. The screening of plasma proteins were carried out using 2-dimensional gel electrophoresis followed by identification of differentially expressed protein by MALDI-TOF MS/MS. Among several differentially expressed proteins, transthyretin (TTR) has been identified as one of the protein that showed significantly up regulated expression in the plasma of RA patients. The results were further validated by Western blot analysis and ELISA. In comparison to OA synovium, an exclusive significantly high expression of TTR in RA has been validated through IHC, Western blotting and IEM studies. Most importantly, the increase in expression of TTR with the progression of severity of RA condition has been observed. The autoantibodies against TTR present in the RA plasma were identified using immunoprecipitation-Western methods. The significant production of autoantibodies was validated by ELISA and Western blot analysis using recombinant pure protein of TTR. Hence, these novel observations on increase in TTR expression with the increase in severity of RA conditions and significant production of autoantibodies against TTR clearly suggest that a systematic studies on the role TTR in the pathogenesis of RA is immediately required and TTR may be used as a serum diagnostic marker together with other biochemical parameters and clinical symptoms for RA screening and diagnosis.