Background: Immunoglobulin D (IgD) remains an enigmatic molecule due to the limited understanding of its function both in healthy and in patients with autoimmune diseases. In this study, we analyse serum IgD (sIgD) levels in rheumatoid arthritis (RA), paying special attention to clinical and serologic features of RA and treatment.
Methods and finding: Serum levels of IgD, IgM, IgG and IgA were measured in 416 subjects (248 RA patients and 169 healthy controls matched by age and gender), by sandwich ELISA. Here, we show that low IgD, but not IgM, IgG and IgA, is associated with female gender and with the presence of RA-specific autoantibodies. Most prominent reduction of sIgD was found in the patients producing rheumatoid factor, alone (p=0.009) and in combination with antibodies to cyclic citrullinated peptides (p= 0.02). Low sIgD was measured in female RA patients below 50 years (p=0.01), but not in healthy females. Additionally, low sIgD was measured in RA patients treated with a combination of methotrexate and sulfasalazine/hydroxichloroquine compared to those receiving methotrexate and biologics (p=0.01).
Conclusion: In RA patients, sIgD levels present clinical associations which distinct it from IgM, IgG and IgA. Low serum IgD levels appears to be pathological and is associated with autoantibodies and certain anti-rheumatic treatment.