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Objective. Microchimerism (Mc), originating from bidirectional fetal-maternal cell traffic during pregnancy, has recently been identified in healthy adults and in patients with scleroderma (systemic sclerosis [SSc]). This study was undertaken to investigate the frequency and quantitative levels of maternal Mc (MMc) in healthy women and women with SSc.Methods. HLA-specific primers and fluorogenic probes were used in real-time quantitative polymerase chain reaction assays to detect and quantify MMc by targeting noninherited, nonshared HLA sequences. DNA-based HLA typing was conducted in 67 probandmother pairs and in all children if the proband was parous. Statistical analysis was limited to 50 probandmother pairs (including 32 healthy women and 18 women with SSc) in whom MMc could be distinguished from potential fetal Mc.Results. MMc in peripheral blood mononuclear cells was more frequent among women with SSc (72%) than healthy women (22%) (odds ratio 9.3, P ‫؍‬ 0.001). However, levels of MMc, expressed as the genome equivalent of maternal cells per million (gEq/mil), were not significantly different (0-68.6 gEq/mil in SSc patients, 0-54.5 in healthy women). In additional studies, positivity for MMc was demonstrated in a bone marrow aspirate from an SSc patient in whom peripheral blood had been found to be negative for MMc on 4 occasions, and tissue from a subsequent autopsy of this patient had MMc levels of 757 and 1,489 gEq/mil in the lung and heart, respectively.Conclusion. MMc is not uncommon in the peripheral blood of healthy adults, is increased in frequency in patients with SSc, and may be present in bone marrow and disease-affected tissues although absent in the peripheral blood.In 1995, Hall et al demonstrated that maternal cell traffic to the fetus is a more common event than previously thought (1). Cord blood samples from male infants were studied using fluorescence in situ hybridization, and female cells were identified in Ͼ20% of the samples. Subsequent studies utilizing nonquantitative polymerase chain reaction (PCR)-based techniques identified maternal DNA with a frequency of 40% (2) to 75% (3) in cord blood samples. Maternal microchimerism (MMc) is not limited to events related to parturition: maternal DNA has also been found in the circulation of fetuses from elective terminations of early and late pregnancies (4,5).Pollack and colleagues, in 1980, showed that maternal cells engraft and persist in the circulation of infants with severe combined immunodeficiency (6). However, it was 19 years later before the long-term persistence of MMc in immunocompetent individuals was investigated. Using a nonquantitative technique, we previously observed the persistence of MMc into adult life in some healthy individuals and in patients with scleroderma (systemic sclerosis [SSc]) (7). The long-

Objective. A number of non-HLA loci that have shown evidence (P < 0.05) for linkage with rheumatoid arthritis (RA) have been previously identified. The present study attempts to confirm these findings.Methods. We performed a second genome-wide screen of 256 new multicase RA families recruited from across the United States by the North American Rheumatoid Arthritis Consortium. Affected sibling pair analysis on the new data set was performed using SIBPAL. We subsequently combined our first and second data sets in an attempt to enhance the evidence for linkages in a larger sample size. We also evaluated the impact of covariates on the support for linkage, using LODPAL.Results. Evidence of linkage at 1p13 (D1S1631), 6p21.3 (the HLA complex), and 18q21 (D18S858) (P < 0.05) was replicated in this independent data set. In addition, there was new evidence for linkage at 9p22 (D9S1121 [P ‫؍‬ 0.001]) and 10q21 (D10S1221 [P ‫؍‬ 0.0002] and D10S1225 [P ‫؍‬ 0.0038]) in the current data set. The combined analysis of both data sets (512 families) showed evidence for linkage at the level of P < 0.005 at 1p13 (D1S1631), 1q43 (D1S235), 6q21 (D6S2410), 10q21 (D10S1221), 12q12 (D12S398), 17p13 (D17S1298), and 18q21 (D18S858). Linkage at HLA was also confirmed (P < 5 ؋ 10 ؊12 ). Inclusion of DRB1‫40ء‬ as a covariate significantly increased the probability of linkage on chromosome 6. In addition, some linkages on chromosome 1 showed improved significance when modeling DRB1‫40ء‬ or rheumatoid factor positivity as covariates.

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