Transplacentally transmitted autoimmune disorders of the fetus and newborn: pathogenic considerations

Autoimmune diseases affect a significant number of women in their childbearing years. This group of disorders constitutes a heterogeneous spectrum with a common basis involving the presence of autoantibodies often of the IgG type. Transplacental transfer of autoantibodies is not uncommon, and autoantibodies can be readily demonstrated in newborn serum. Only a small proportion of infants with circulating autoantibodies exhibit clinical symptoms. The transient neonatal manifestations of maternal autoimmune disease disappear over a time course consistent with the catabolism of IgG, providing no permanent damage occurs. Thus the pathogenic role of transferred autoantibodies seems well established. However, maternal-autoantibody-mediated tissue damage appears to depend on factors other than the mere passage of the antibody to the fetal compartment. This review details putative factors that are likely to modulate the clinical expression of the fetal antigen-autoantibody reaction in offspring of mothers with autoimmune disorders. The importance of amount, type, and specificity of autoantibodies is described. The possible significance of fetal and maternal immunogenetics is briefly discussed, as well as the limited knowledge currently available on the fetal development of fetal antigenic sites at target organs. These and other as yet unidentified factors may help explain the rarity of clinical manifestations in infants exposed to potentially pathogenic maternal autoantibodies.