Maternal and sibling microchimerism in twins and triplets discordant for neonatal lupus syndrome-congenital heart block.
OBJECTIVE
Neonatal lupus syndrome-congenital heart block (NLS-CHB) is an acquired autoimmune disease in which maternal autoantibodies are necessary but not sufficient for disease. Maternal myocardial cells have been found in the hearts of patients with NLS-CHB, suggesting that maternal microchimerism may also play a role. In this study we asked whether levels of microchimerism in the blood are associated with NLS-CHB in discordant twins and triplets.


METHODS
Human leucocyte antigen (HLA)-specific and Y-chromosome-specific real-time quantitative polymerase chain reaction (PCR) was used to quantitatively assay maternal and sibling microchimerism in peripheral blood. Because of HLA allele sharing in families, it was not always possible to distinguish between multiple sources of microchimerism.


RESULTS
In one family, maternal and/or sibling microchimerism was detected in two triplets who had CHB, but not in the triplet with transient hepatitis. Levels ranged from 4 to 948 genome-equivalents of foreign deoxyribonucleic acid per million host genome-equivalents (gEq/million). Over the first year levels of sibling microchimerism decreased in the triplet with complete CHB and increased in the triplet who progressed from first- to second-degree CHB. In a second family, maternal and/or sibling microchimerism was detected in the healthy twin (1223 gEq/million) but not in the twin with CHB.


CONCLUSIONS
Maternal and/or sibling microchimerism was detectable in the blood of infant twins and triplets discordant for NLS. Microchimerism in the blood was not specific for NLS-CHB, although in one family levels correlated with disease. Thus, microchimerism in the blood and/or tissues may be involved in the pathogenesis or progression of NLS-CHB, but additional factors must also contribute. Further investigation is warranted.
Stevens
A M
AM
Immunogenetics, D2-100, P.O. Box 19024, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, Seattle, WA 98109, USA. astevens@fhcrc.org
Hermes
H M
HM
Lambert
N C
NC
Nelson
J L
JL
Meroni
P L
PL
Cimaz
R
R
D046528:Chimerism; D041322:Chromosomes, Human, Y / Q000235:genetics; D004247:DNA / Q000032:analysis; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000032:analysis; D006327:Heart Block / Q000151:congenital / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008431:Maternal-Fetal Exchange / Q000235:genetics; D009035:Mothers; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D013577:Syndrome; D014310:Triplets / Q000235:genetics; D014427:Twins / Q000235:genetics
D006680:HLA Antigens; D004247:DNA