Microchimerism in the Rheumatoid Nodules of Patients with Rheumatoid Arthritis

Objective: The rheumatoid nodule is a lesion commonly found on extraarticular areas prone to mechanic trauma. When present with inflammatory symmetric polyarthritis, it is pathognomonic of rheumatoid arthritis (RA), an autoimmune disease in which naturally acquired microchimerism has previously been described and can sometimes contribute to RA risk. Since RA patients harbor microchimerism in the blood, we hypothesized that microchimerism is also present in rheumatoid nodules and could play a role in rheumatoid nodule formation. This study was undertaken to investigate rheumatoid nodules for microchimerism.

Methods: Rheumatoid nodules were tested for microchimerism by real-time quantitative polymerase chain reaction (qPCR). The rheumatoid nodules of 29 female patients were tested for a Y chromosome-specific sequence. After HLA genotyping of patients and family members, rheumatoid nodules from 1 man and 14 women were tested by HLA-specific qPCR, targeting a nonshared HLA allele of the potential microchimerism source. Results were expressed as genome equivalents of microchimeric cells per 10(5) patient genome equivalents (GE/10(5)).

Results: Rheumatoid nodules from 21% of the female patients contained male DNA (range <0.5, 10.3 GE/10(5)). By HLA-specific qPCR, 60% of patients were microchimeric (range 0, 18.5 GE/10(5)). Combined microchimerism prevalence was 47%. A fetal or maternal source was identified in all patients who tested positive by HLA-specific qPCR. Unexpectedly, a few rheumatoid nodules also contained microchimerism without evidence of a fetal or maternal source, suggesting alternative sources.

Conclusion: Our findings indicate that microchimerism is frequently present in the rheumatoid nodules of RA patients. Since microchimerism is genetically disparate, whether microchimerism in rheumatoid nodules serves as an allogeneic stimulus or allogeneic target warrants further investigation.