Quantification of maternal microchimerism by HLA-specific real-time polymerase chain reaction: studies of healthy women and women with scleroderma

Arthritis Rheum. 2004 Mar;50(3):906-14. doi: 10.1002/art.20200.

Abstract

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 proband-mother pairs and in all children if the proband was parous. Statistical analysis was limited to 50 proband-mother 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow / pathology
  • Case-Control Studies
  • Chimera*
  • Computer Systems
  • Female
  • Gene Frequency
  • HLA Antigens / genetics*
  • Humans
  • Middle Aged
  • Monocytes / pathology
  • Mothers*
  • Odds Ratio
  • Polymerase Chain Reaction*
  • Scleroderma, Localized / genetics*
  • Scleroderma, Localized / immunology*
  • Scleroderma, Localized / pathology

Substances

  • HLA Antigens