Skewing of pretransplant anti-HLA class I antibodies of immunoglobulin G isotype solely toward immunoglobulin G1 subclass is associated with poorer renal allograft survival

Sensitized patients with lymphocytotoxic immunoglobulin (Ig)G anti-human leukocyte antigen (HLA) antibodies have an increased risk of rejection and poorer graft survival. Little is known, however, about the correlation between IgG antibody subclass and clinical outcomes. We identified 20 sensitized renal transplant recipients (panel reactive antibody > 15%), all of whom had anti-HLA class I antibodies of an IgG isotype with known specificity before transplantation but who received a crossmatch negative graft. We analyzed the degree of skewing solely toward IgG(1) (n = 11) or to other IgG subclasses with or without IgG(1) (n = 9) and correlated these findings with graft survival. At last follow-up (median follow-up 28 months), 6 of 11 patients (55%) with anti-HLA antibodies skewed toward IgG, had lost their grafts compared with 0 of 9 patients (0%) with anti-HLA antibodies not skewed toward IgG, (P = 0.01 log-rank test). Anti-HLA antibodies of an IgG, subclass may be a novel marker predicting poor graft outcome.