Myocardial-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block.
BACKGROUND
During pregnancy, maternal cells pass into the fetus, where they can persist for many years after birth. We investigated the presence of maternal cells in neonatal lupus syndrome (NLS), an autoimmune disease that develops in utero. The most serious complication of NLS is inflammation of the atrioventricular node leading to congenital heart block (CHB).


METHODS
In a blinded case-control study, maternal (female) cells were detected and quantified in male NLS and control heart-tissue samples. We used fluorescence in-situ hybridisation to label X and Y chromosomes. Studies in transplantation suggest that donor cells can differentiate into somatic tissue cells. Therefore, we asked whether maternal cells transferred in utero have cellular plasticity. To simultaneously identify and characterise maternal cells, we developed a technique by which multiple phenotypic markers could be detected concurrently with fluorescence in-situ hybridisation in the same cells of a tissue section.


RESULTS
Maternal cells were found in 15 of 15 sections of NLS heart tissue, ranging from 0.025% to 2.2% of total cells. By contrast, maternal cells were found in two of eight control sections (0-0.1%). Very few maternal cells expressed the haemopoietic cell marker CD45. Most expressed sarcomeric alpha actin, a specific marker for cardiac myocytes.


CONCLUSIONS
Our findings suggest that differentiated tissue-specific maternal microchimerism can occur in neonates. Thus, semiallogeneic maternal cells could be the target of an immune response. Alternatively, maternal cells could contribute to a secondary process of tissue repair.
Stevens
Anne M
AM
Fred Hutchinson Cancer Research Center, Immunogenetics, Seattle, WA 98109, USA. astevens@fhcrc.org
Hermes
Heidi M
HM
Rutledge
Joe C
JC
Buyon
Jill P
JP
Nelson
J Lee
JL
D016022:Case-Control Studies; D002454:Cell Differentiation; D002678:Chimera; D005260:Female; D005315:Fetal Diseases / Q000473:pathology*; D006321:Heart / Q000196:embryology*; D006327:Heart Block / Q000150:complications / Q000151:congenital* / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000151:congenital* / Q000473:pathology*; D008297:Male; D008431:Maternal-Fetal Exchange; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D011247:Pregnancy