Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients

Abstract

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. Analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p < 0.004). Patients carrying the DR2 alleles, DRB1*1501, *1502 or *1601 were at a lower risk of producing anti-donor HLA antibodies.

A Comparative Analysis Between Survivors and Nonsurvivors with Antibody Mediated Cardiac Allograft Rejection

“…It is important to note that most patients in our series died of chronic rejection, with acute rejection in a close second. Both these pathological processes have been associated with allo-antibodies [10,[13][14][15][16][17]. To our knowledge, this is the first time that the pretransplant MESF has to be associated to death.…”

Preformed and De Novo Donor Specific Antibodies in Visceral Transplantation: Long-Term Outcome With Special Reference to the Liver

“…Although persistence of class-II DSA after transplantation may indicate that these antibodies exhibit a spectrum of deleterious effects, an alternative interpretation is the allograft absorption of pathogenic class-I DSA. Other immunobiologic variables that may modulate the harmful effects of DSA include intrinsic characteristics, binding affinity to recognized epitopes, spectrum of epitopes within HLA molecules and presence of antiidiotypic antibodies (9,10,(48)(49)(50)(51)(52).…”

Alloantibodies in heart transplantation

“…We later unraveled the protective effect of anti-idiotypic antibodies that block binding of Ab1 to the graft. In subsequent studies, we showed that activation of the indirect recognition pathway and persistent reactivity to donor allopeptides is associated with rejection and accounts for T-cell-dependent differentiation of alloantibody-producing B cells [3][4][5][6][7][8]. More recently, we discovered the importance of immunoregulatory networks comprising T-suppressor cells, and professional as well as nonprofessional antigen-presenting cells (APC) in maintaining quiescence in heart allograft recipients [9 -11].…”