Pediatric Rheumatology Online Journal → July 2003 → Childhood Lupus→ Immunology and Immunogenetics → Abstract #91

MATERNAL AND FRATERNAL MICROCHIMERISM IN NULLIGRAVID FEMALES WITH AUTOIMMUNE DISEASE

A. M. Stevens,^1,2,3 N. C. Lambert,¹ H. M. Hermes,¹ T. E. Erickson,¹ J. L. Nelson.^1,4

¹Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; ²Pediatrics, University of Washington, Seattle, WA, United States; ³Rheumatology, Children's Hospital and Regional Medical Center, Seattle, WA, United States; ⁴Medicine, University of Washington, Seattle, WA, United States

Transfusion of parental lymphocytes into a mouse leads to a type of graft-versus-host disease with characteristics similar to systemic lupus erythematosus (SLE), with glomerulonephritis and anti-nuclear antibodies. In humans, maternal cells traffic into fetal circulation and have recently been shown to persist for years, leading to the hypothesis that maternal cells could be involved in the development of SLE. To test this hypothesis we used Real-Time Quantitative PCR specific for non-inherited maternal HLA, GST, and ACE alleles to detect maternal DNA in peripheral blood cells from pediatric SLE patients and healthy controls. We detected maternal DNA in 4 of 10 SLE patients vs. 9 of 34 controls (40% vs 26%, p = ns). The levels in SLE were similar to those in controls (mean 31 per million, range 1-91 vs. 31, range 5-65). By fluorescence n situ hybridization for X- and Y-chromosome-specific sequences, maternal cells (XX) were found in blood from two of four male (XY) SLE patients. Since fetal DNA persists in women after pregnancy, a child could potentially harbor cells from an older sibling. We used Q-PCR for the DYS14 Y-chromosome specific sequence to test nulligravid female subjects with older brothers for male DNA. Six of 18 pediatric SLE patients were positive for male DNA (33%, mean 1.5 per million, range 0.3-3.5) compared to 0 of 9 controls. In two SLE patients both Y-chromosome DNA and maternal DNA were detected. This study suggests that fetal cells persisting in a woman's blood can be transferred years later to her next child, creating fraternal microchimerism. These allogeneic sibling-derived cells were found in SLE, but not in controls. Both maternal cells and fraternal cells can coexist in the same patient, increasing the probability of pathogenic alloreactivity due to interactions between maternal/host, fraternal/host and maternal/fraternal cells, which could lead to the chronic inflammation of autoimmune disease.