Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
The Clinical Features of 13 Women with Microchimerism in Rheumatoid Nodules.
Atkins4, Christopher J., Chan1, William F. N., Naismith6, David, van der Westhuizen6, Nicholas, Woo3, Janet, Cortez5, Valerie, Nelson2, J. Lee
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center and University of Washington
University of British Columbia
University of Victoria, Victoria, BC, Canada
University of Washington
Vancouver Island Health Authority
Non-caseating granulomatous nodules in the setting of an inflammatory symmetrical polyarthritis have a high degree of diagnostic specificity for rheumatoid arthritis (RA). The pathogenesis of the rheumatoid nodule (RN) is unknown, although its growth over pressure points suggests a role for trauma. An increase in microchimerism (Mc) has been reported in the blood of RA patients, therefore we reasoned that microtrauma triggers an allogenic response to michrochimeric cells in the formation of the RN.
To investigate Mc in RNs from women by testing for male DNA.
1. DNA extraction from 19 nodules collected from 15 female patients followed by quantitative PCR on the Y-chromosome specific sequence DYS14; 2. Review of clinical features of women whose RNs contained male DNA, including treatment with methotrexate and anti-TNF biologics, both of which have been associated with RN formation; 3. Comparison of the concentration of Mc in RN, expressed as genome equivalents (gEq) of male-specific DYS14 DNA per 100,000 cells, to serum concentration of anti-cyclic citrullinated peptide (CCP) antibodies.
Fourteen nodules from 13 patients were positive for Mc. Mean age of RA onset was 43 years (range 2664). The most common source of male DNA in a woman is prior birth of a son. Eight of 13 patients had given birth to sons, seven with sons born before (mean time from birth 19 years; range 038) and one after RA onset. Blood transfusion is an alternative potential source of Mc. The patient whose son was born after RA onset had received blood transfusions 1 and 4 years before disease onset. Mc can also originate from a miscarriage. The 5 patients without sons but positive for Mc had no history of miscarriage or transfusion. Two had daughters and one received gamma globulin 2 years before disease onset.
All patients presented with a symmetrical inflammatory polyarthritis. Eleven of 13 patients had erosions on X-ray. Twelve patients received methotrexate, all of whom developed RN after therapy, with 6 patients following the addition of a biologic. Two developed accelerated RN formation with methotrexate, one after the addition of infliximab. Eleven of 13 patients tested positive for rheumatoid factor. Twelve of 13 patients had a concentration of anti-CCP that is above the reference range (05 U/ml), with 7 patients >100 U/ml. Eight patients with a concentration of anti-CCP >50 U/ml (range 58 to >100) had a Mc concentration of <1 gEq (range 0.080.78). In contrast, 4 of 5 patients with a concentration of anti-CCP <50 U/ml (range 334) had a Mc concentration of >1 gEq (range 1.577.51).
The clinical features of 13 women with RA whose nodules contained male DNA were typical of those usually associated with severe disease. In 7 patients, the nodules appeared several years after the birth of their male offspring, suggesting a fetal origin for the foreign DNA. Unrecognized miscarriage, induced abortion, or transfer of cells from an older male sibling are potential sources of male DNA in the 5 women who did not have sons, known miscarriages, or transfusions. Patients with the highest Mc concentrations had the lowest anti-CCP concentrations, suggesting an inverse relationship.
To cite this abstract, please use the following information:
Atkins, Christopher J., Chan, William F. N., Naismith, David, van der Westhuizen, Nicholas, Woo, Janet, Cortez, Valerie, et al; The Clinical Features of 13 Women with Microchimerism in Rheumatoid Nodules. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1060