Background/Purpose: Microchimerism (Mc) is naturally acquired through bi-directional exchange of small amounts of cells or DNA between mother and fetus during pregnancy. Higher amounts of maternal Mc (MMc) have been reported in peripheral blood of patients suffering from autoimmune diseases such as systemic sclerosis (SSc), compared to healthy controls (1,2), however, it is unknown what cell type(s) is responsible for this increase. We investigated the frequencies and quantitative levels of MMc within cellular subsets isolated from peripheral blood mononuclear cells (PBMC) in patients with SSc and compared results to healthy controls.

Methods : 69 subjects were studied for MMc in T cells, B cells, NK cells and monocyte/macrophages, including 27 female patients with SSc and 42 healthy controls (32 female and 10 male). To detect and identify MMc, HLA-specific primers and fluorogenic probes were used in quantitative polymerase chain reaction (Q-PCR), targeting the non-inherited, non-shared maternal HLA allele. Therefore, HLA genotyping was performed for all the subjects and their mothers. When non-inherited maternal HLA was indistinguishable from subject’s HLA, primers and probes targeting non-HLA polymorphisms developed for this purpose were used. Using fluorescence-activated cell sorting, PBMC were sorted into: T, B, and NK cells, and monocyte/macrophages to an average purity of 98.6%. The specific Q-PCR assays were then undertaken on DNA extracted from individual subsets. Prevalence of MMc was analyzed using logistic regression, and negative binomial regression model was used to asses MMc quantitative levels, with adjustment for total number of genome equivalents tested.

Results: MMc was identified in at least one cellular subset in 44.4% of SSc patients and 40.5% of healthy subjects, without a significant difference between patients and controls overall, or when comparing each subpopulation separately. However, MMc levels were significantly higher in SSc patients compared to controls, with an incidence rate ratio (IRR) of 47.4 (P < 0.001). Interestingly, the difference in MMc levels was greater in the adaptive immune subpopulations (IRR_{[T cells]} = 109.1 and IRR_{[B cells]} = 51.2; P < 0.001) compared to those of the innate immune cells (IRR_{[NK cells]} = 29.8; P = 0.001 and IRR_[Monocytes] = 6.3; P = 0.117).

Conclusion : We found higher amounts of MMc especially in adaptive immune cellular subsets in women with SSc compared to healthy controls. This incites further investigation of the immunologic functionality of MMc in health and disease, which is currently under way.

References:

1. Lambert, et al. Arthritis Rheum. 2004 Mar;50(3):906-14
2. Nelson JL. Trends Immunol. 2012 Aug;33(8):421-7

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/maternal-microchimerism-is-increased-in-multiple-cellular-subsets-of-patients-with-systemic-sclerosis-compared-to-healthy-controls/