Immunologic evaluation during the first year of life of infants born to cyclosporine-treated female kidney transplant recipients - Analysis of lymphocyte subpopulations and immunoglobulin serum levels

Background, In rodents, CsA has been shown to affect T-cell development, gi ving rise to an abnormal production of mature T cells and the absence of ma ny T-cell subsets as well as to autoimmunity. Surprisingly, only a few stud ies investigated the effect of the immunosuppressive drug on the immune sys tem of the human fetus. Methods, We examined six infants born to female kidney transplant recipient s who had received cyclosporine and methylprednisolone throughout their pre gnancies. Peripheral blood was obtained 1 day and 2, 4, 6, and 12 months af ter birth, and two-color flow cytometric immunophenotyping of lymphocytes w as performed. Results. Total T cells, as well as CD4(+) and CD8(+) T cells, were low at b irth, but normalized thereafter, Among T-cell activation markers, the expre ssion of CD25, the alpha chain of the interleukin-a receptor, was below the normal range or low range throughout the study period, and HLA-DR expressi on was extremely low at birth and failed to increase up to 12 months, The n umber of total B cells was lower than normal at birth, but steeply increase d over time. In contrast, B-cell subset bearing CD5 antigen was severely de pleted throughout the first year of life, Total IgG concentration was signi ficantly lower than in controls at 2 months, mainly because of subnormal le vels of IgG1 and IgG3 subclasses, which remained in the low range up to 6 m onths. Finally, infants showed normal numbers of true natural killer (NK) c ells (CD3(-)CD16(+)CD56(+)), whereas the expression of CD57 antigen, defini ng non-MHC-restricted cytotoxic lymphocytes, was barely detectable at birth and failed to increase over time, in both CD8(+) and CD8(-) subsets. Of no te, none of the infants had clinical evidence of an immunodeficient state. Conclusions. continuous exposure to CsA in utero seemingly impairs T-, B-, and NK-cell development and/or maturation, and most of its effects are stil l apparent at 1 year, which might suggest that conventional vaccinations sh ould be delayed in these infants.