HLA class I noninherited maternal antigens in cord blood and breast milk

Maternally induced allotolerance both in clinical and experimental organ transplantation appears to require both in utero and oral exposure to noninherited maternal antigens (NIMA). Soluble major histocompatibility complex (MHC) class I antigens were studied in 18 mother-baby pairs in order to determine the extent of neonatal exposure to NIMA. Enzyme-linked immunoabsorbent assay (ELISA) analysis of cord blood from three genetically HLA-A2 negative babies born to HLA-A2+ mothers and from two HLA-A3 negative babies born to HLA-A3+ mothers revealed significant NIMA HLA-A levels in cord plasma. The level of NIMA-A2 or -A3 in cord blood were approximately 10% of the predicted value for a baby genetically positive for that allele. HLA-A2 or -A3 was undetectable (< 1.0 ng/ml) in cord blood from HLA-A2 or -A3 negative babies whose mothers were also HLA-A2 or -A3 negative. Breast milk from HLA-A2+ mothers contained soluble HLA-A2 (sHLA-A2) at levels averaging 36.2 ng/ml, resulting in milligram quantities of ingested antigen over 3 months of nursing. Western blot analysis of cord plasma confirmed that bands corresponding to NIMA HLA-A protein were present. This study demonstrates that oral and intravenous exposure to NIMA sHLA in the fetus and newborn is much higher than previously thought, and emphasizes the importance of nursing in the overall antigen dose achieved.