FETAL-MATERNAL HLA COMPATIBILITY CONFERS SUSCEPTIBILITY TO SYSTEMIC-SCLEROSIS

Systemic sclerosis (SSc) is a disease of unknown origin, which occurs predominantly in women after childbearing years. There art prominent c linical and histopathologic similarities between SSc and chronic graft -versus-host disease (GVHD). GVHD can occur after blood transfusions o r after transplantation with HLA-compatible bone marrow. Here we exami ned the hypothesis that SSc map be caused by fetal cells crossing the placenta into the maternal circulation and providing donor lymphocytes which recognize disparate HLA antigens, resulting in a reaction simil ar to chronic GVHD. To test the hypothesis we analyzed the inheritance of HLA class I and class II haplotypes in the families of 37 SSc pati ents and 42 control individuals. Twenty-six (70.2%) SSc patients had H LA class II alleles compatible either for their offspring or mother, c ompared with only nine (21%) control individuals. The four patients wi th juvenile onset SSc we analyzed had alleles compatible with their mo thers. These results suggest that in some patients, SSc may, indeed, b e a form of chronic GVHD caused by fetal or maternal cells which have crossed the placenta during pregnancy and have remained unrecognized b y the host due to class II HLA compatibility. and that subsequent acti vation of these cells by as yet unknown stimuli result in the developm ent of the disease.