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, giving rise to an abnormal production of mature T cells and the absence of many T-cell subsets as well as to autoimmunity. Surprisingly, only a few studies investigated the effect of the immunosuppressive drug on the immune system of the human fetus.


METHODS
We examined six infants born to female kidney transplant recipients who had received cyclosporine and methylprednisolone throughout their pregnancies. Peripheral blood was obtained 1 day and 2, 4, 6, and 12 months after birth, and two-color flow cytometric immunophenotyping of lymphocytes was performed.


RESULTS
Total T cells, as well as CD4+ and CD8+ T cells, were low at birth, but normalized thereafter. Among T-cell activation markers, the expression of CD25, the alpha chain of the interleukin-2 receptor, was below the normal range or low range throughout the study period, and HLA-DR expression was extremely low at birth and failed to increase up to 12 months. The number of total B cells was lower than normal at birth, but steeply increased over time. In contrast, B-cell subset bearing CD5 antigen was severely depleted throughout the first year of life. Total IgG concentration was significantly lower than in controls at 2 months, mainly because of subnormal levels of IgG1 and IgG3 subclasses, which remained in the low range up to 6 months. Finally, infants showed normal numbers of true natural killer (NK) cells (CD3-CD16+CD56+), whereas the expression of CD57 antigen, defining non-MHC-restricted cytotoxic lymphocytes, was barely detectable at birth and failed to increase over time, in both CD8+ and CD8- subsets. Of note, 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 still apparent at 1 year, which might suggest that conventional vaccinations should be delayed in these infants.
Di Paolo
S
S
Department of Emergency and Organ Transplant, University of Bari Policlinico, Italy.
Schena
A
A
Morrone
L F
LF
Manfredi
G
G
Stallone
G
G
Derosa
C
C
Procino
A
A
Schena
F P
FP
D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D001724:Birth Weight; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D016030:Kidney Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008775:Methylprednisolone / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors
D015703:Antigens, CD; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008775:Methylprednisolone