SUPPRESSION OF HLA-SPECIFIC ALLOANTIBODIES BY HIGH-DOSE INTRAVENOUS IMMUNOGLOBULINS (IVIg)

Therapeutic preparations of IVIg contain naturally occurring anti–HLA-E antibodies that react with HLA-Ia (HLA-A/-B/-Cw) alleles

“…[2][3][4][5] This investigation documents that IVIg per se contains reactivity to most of the HLA-Ia alleles (Table 2). Hence, it is doubtful that IVIg can lower HLA antibodies, particularly when IVIg by itself contains high HLA-Ia Abs reactivities.…”

“…26 Various mechanisms have been proposed for lowering anti-HLA Abs by IVIg. Though it was suggested that anti-idiotypic antibodies against anti-HLA Abs in IVIg might be responsible for the reduction of pretransplant or de novo HLA Ab, [2][3][4] Barocci et al 27 failed to detect anti-idiotypic Abs (Ab2 directed against Ab1 anti-HLA) in several IVIg preparations. Another possibility is that IVIg binds through the Fc portion of IgG to the inhibitory FcgRIIb that is expressed on a variety of blood cells, including B cells, leading to the reduction of proliferation and apoptosis induction.…”

“…Since that time, IVIg has emerged as a potential treatment strategy for desensitization protocols and also for lowering the incidence of donor-specific Abs (DSA) involved in Ab-mediated rejection (AMR). Several transplant centers [2][3][4][5][6][7][8] have adopted the protocol of IVIg administration for patients awaiting transplantation and for allograft recipients in order to reduce allo-HLA Abs or DSA directed against the HLA of donor kidneys.…”

Antibody-Mediated Rejection in Renal Allografts

“…Protocols that are similar to those used for treating AMR after transplantation also have proved useful in eliminating antibodies to donor HLA and ABO blood group antigens that existed before transplantation in sensitized patients, thereby allowing for successful transplantation of kidneys across these previously unscalable immunologic barriers (31,(35)(36)(37)(38)(39)(40). In biopsies of initially HLA-incompatible renal allografts, including biopsies that were performed for graft dysfunction and protocol biopsies of stably functioning grafts, we have found a strong association between PTC C4d staining and neutrophil margination, similar to findings in cases with a negative pretransplantation cross-match.…”

The Evaluation of the Renal Transplant Candidates: Clinical Practice Guidelines

“…Over the past decade, several clinical trials of procedures designed to reduce titers of alloantibodies, e.g. plasmapheresis, immunoadsorption, intravenous immunoglobulin and intensified immunosuppression, have yielded promising, albeit preliminary results (1096,(1106)(1107)(1108)(1109)(1110)(1111).…”