Myocardial-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block

• Published in: The Lancet (British edition) 2003-11, Vol.362 (9396), p.1617-1623
• Main Authors: Stevens, Anne M, Hermes, Heidi M, Rutledge, Joe C, Buyon, Jill P, Nelson, J Lee
• Format: Article
• Language: English
• Subjects: Actin; Autoimmune diseases; Calcification; Cardiomyocytes; Cardiovascular disease; Case-Control Studies; CD45 antigen; Cell Differentiation; Cells; Children & youth; Chimera; Chimerism; Chromosomes; Congenital diseases; Congenital heart block; Disease; Female; Fetal Diseases - pathology; Fetuses; Fluorescence; Heart; Heart - embryology; Heart Block - complications; Heart Block - congenital; Heart Block - pathology; Hematopoietic Stem Cells - pathology; Hepatitis; Hospitals; Humans; Immune response; Immune system; In Situ Hybridization, Fluorescence; Infant; Infant, Newborn; Laboratories; Liver; Lupus; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - congenital; Lupus Erythematosus, Systemic - pathology; Male; Maternal-Fetal Exchange; Medical research; Myocardium - pathology; Myocytes; Neonates; Newborn babies; Pathogenesis; Phenotype; Phenotypes; Plastic foam; Pregnancy; Systemic lupus erythematosus; Tissue engineering; Tissues; Transplantation; Y chromosomes
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(03)14795-2

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). 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. 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 α actin, a specific marker for cardiac myocytes. 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.