Abstract

The immunoglobulin A isotypes of anti-cyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) are associated with disease severity and progression in Caucasian rheumatoid arthritis (RA) patients, as well as with genetic predisposition and tobacco use. To compare levels of ACPA-IgA and RF-IgA with those of ACPA-IgG and cRF in a cohort of black South African RA patients and healthy controls.To investigate the relationship between IGA autoantibodies and disease severity, genetic predisposition and tobacco use. RF-IgA and ACPA-IgA were determined in a cohort of predominantly black South African RA patients (n=75) in relation to serodiagnostic and prognostic potential, as well as tobacco use and genetic predisposition. Healthy control subjects were included to determine sensitivity, specificity and predictive values.ACPA-IgG/IgA and RF-IgA were determined by enzyme immunoassay and hs-CRP and cRF by nephelometry. Cotinine levels were determined by ELISA. The frequencies of ACPA-IgA and RF-IgA were 31% and 88% respectively compared to 88% for both types of traditional autoantibody procedures. ACPA-IgA was significantly higher (p=0.007) in patients with short disease duration, while linear regression analysis revealed a positive relationship with baseline disease activity scores. Levels of ACPA-IgG and ACPA-IgA were significantly higher in tobacco users who carried the HLA shared epitope. Although lacking in serodiagnostic superiority over cRF and ACPA-IgG, inclusion of RF-IgA and ACPA-IgA in autoantibody panels may provide insights into disease pathogenesis, interactions between tobacco usage and HLA genotype in the production of potentially disease-triggering ACPA-IgA antibodies.

Highlights

  • Introduction femalesThe inclusion of measurement of rheumatoidRheumatoid arthritis (RA) is a crippling disease charac- factor (RF) and anti-citrullinated peptide (ACPA) antiterized by chronic inflammation of the articular joints bodies, generally composite rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA)-IgG, of patients leading to cartilage destruction and disease in the 2010 ACR/EULAR rheumatoid arthritis (RA) classification criteria is an progression

  • Less is known about the diagnostic and prognostic potential of measurement of ACPA and RF auto-antibodies of the immunoglobin A (IgA) isotype in other ethnicities with RA, as well as their associations with prominent disease risk factors, tobacco use and positivity for the human leucocyte antigen - shared epitope (HLA-SE). These issues have been addressed in the current study in which the levels and prevalence ACPA-IgA and RFIgA auto-antibodies have been compared with those of ACPA-IgG and composite RF (cRF) in a cohort of disease-modifying anti-rheumatic drug (DMARD)-naïve, black, predominantly female, South African patients with RA, and a control group of healthy individuals, the findings of which may be broadly applicable to other populations.Additional aims included investigation of the relationships of these IgA auto-antibodies with: i) disease severity as measured by the simplified disease activity score (SDAI); and ii) genetic predisposition and tobacco use

  • The current study demonstrates a lack of diagnostic or predictive value of measurement of RF-IgA relative to that of cRF in this study group of DMARD-naïve, African RA patients

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Summary

Introduction

Introduction femalesThe inclusion of measurement of rheumatoidRheumatoid arthritis (RA) is a crippling disease charac- factor (RF) and anti-citrullinated peptide (ACPA) antiterized by chronic inflammation of the articular joints bodies, generally composite RF (cRF) and ACPA-IgG, of patients leading to cartilage destruction and disease in the 2010 ACR/EULAR RA classification criteria is an progression. Less is known about the diagnostic and prognostic potential of measurement of ACPA and RF auto-antibodies of the IgA isotype in other ethnicities with RA, as well as their associations with prominent disease risk factors, tobacco use (i.e. cigarettes and snuff) and positivity for the human leucocyte antigen - shared epitope (HLA-SE) These issues have been addressed in the current study in which the levels and prevalence ACPA-IgA and RFIgA auto-antibodies have been compared with those of ACPA-IgG and cRF in a cohort of disease-modifying anti-rheumatic drug (DMARD)-naïve, black, predominantly female, South African patients with RA, and a control group of healthy individuals, the findings of which may be broadly applicable to other populations.Additional aims included investigation of the relationships of these IgA auto-antibodies with: i) disease severity as measured by the simplified disease activity score (SDAI); and ii) genetic predisposition and tobacco use.

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