Maternal microchimerism in muscle biopsies from children with juvenile dermatomyositis

Abstract

Objective: Recent advances in molecular techniques have revealed that there is bi-directional transfer of cells between mother and child during pregnancy, and the presence of a mother's cells in her child has been termed maternal microchimerism (MMc). There is the potential for maternal cells to provoke inappropriate immune responses in the child, which could be a factor in autoimmunity including JDM. The aim of this study was to determine whether maternal (female) cells could be detected in frozen muscle sections from seven males (age range 3-13 years) with JDM participating in the Juvenile Dermatomyositis National (U.K. and Ireland) Cohort Biomarker Study and Repository for Idiopathic Inflammatory Myopathies and sections of muscle controls (age range 2-12 years).

Methods: At least 1000 cells from each section underwent FISH and confocal imaging through each nucleus. Concomitant IF for CD45 was used to determine whether MMc in muscle were lymphocytes. A non-parametric Mann-Whitney U-test was used to detect statistical differences.

Results: The frequency of MMc was higher in JDM muscle (0.42-1.14%) than in controls (0.08-0.42%) P = 0.01. No CD45+ MMc were observed.

Conclusion: These data confirm an increased frequency of MMc in JDM. More detailed characterization of MMc is required, particularly using phenotypic markers, to explain the role of these cells in JDM.

Fig. 1

Confocal imaging through a maternal cell (highlighted by arrow). The X chromosome is indicated by a red dot and the Y chromosome by a green dot. The nucleus is stained blue with DAPI. Imaging through this maternal cell, 2 X chromosomes (and no Y chromosomes) are observed.

Fig. 2

Female (presumed maternal) cells identified in male JDM tissue from three JDM cases. The X chromosome is shown by a red dot, the Y chromosome by a green dot and the nucleus with DAPI (blue).

Fig. 3

Maternal cells identified in JDM biopsies do not express CD45. FISH staining as in Fig. 1. CD45⁺ lymphocytes (stained with FITC–green) were observed in JDM tissue, but no CD45⁺ MMc were observed.