Objective
The rheumatoid nodule (RN) is a lesion commonly found on extra-articular areas prone to mechanical trauma. When present with inflammatory symmetrical polyarthritis, it is pathognomonic of rheumatoid arthritis (RA), an autoimmune disease in which naturally acquired microchimerism (Mc) has previously been described and could sometimes contribute to RA risk. Since RA patients harbor Mc in blood, we hypothesized that Mc is also present in RNs, and could play a role in RN formation. Thus, the current study investigated RNs for Mc.
Methods
RNs were tested for Mc by real-time quantitative PCR (qPCR). For 29 female patients, their RNs were tested for a Y-chromosome specific sequence. Further, after human leukocyte antigen (HLA) genotyping patients and family members, RNs from one male and 14 females were tested by HLA-specific qPCR targeting a non-shared HLA allele of the potential Mc source. Results were expressed as genome equivalents of microchimeric cells per 105 patient genome equivalents (gEq/105).
Results
RNs from 21% of female patients contained male DNA (range: <0.5–10.3 gEq/105). By HLA-specific qPCR, 60% of patients were microchimeric (range: 0–18.5 gEq/105). Combined Mc prevalence was 47%. A fetal or maternal source was identified in all patients who tested positive by HLA-specific qPCR. Unexpectedly, a few RNs also contained Mc without evidence for a fetal or maternal source, suggesting alternative sources.
Conclusion
Mc was frequently found in RNs of RA patients. As Mc is genetically disparate, whether Mc in RNs serves as an allogeneic stimulus or allogeneic target warrants further investigation.