Posttransplant Therapy Using High-Dose Human Immunoglobulin (Intravenous Gammaglobulin) to Control Acute Humoral Rejection in Renal and Cardiac Allograft Recipients and Potential Mechanism of Action1

Abstract

I.v.IG appears to be an effective therapy to control posttransplant AR episodes in heart and kidney transplant recipients, including patients who have had no success with conventional therapies. Vascular rejection episodes associated with development of donor-specific cytotoxic antibodies appears to be particularly responsive to i.v.IG therapy.

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.…”

“…Table 5 provides the profiles of such shared amino acid sequences or epitopes. These shared epitopes were identified, 14(Tab1,4) localized on the heavychain polypeptide, 15 synthesized, and applied in order to inhibit the HLA-E binding of anti-HLA-E mAbs MEM-E/02, 14(Fig2,4B,C,E) 3D12, 15 and sera of normal, healthy nonalloimmunized males. 14 Therefore, it is reasonable to conclude that anti-HLA-E polyclonal Abs in IVIg may be recognizing 1 or more such shared peptides in both HLA class-Ia and -Ib alleles.…”

“…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.…”

Immunosuppressive therapy after human lung transplantation

“…A treatment modality, which deserves a special mention, is the infusion of high-dose (2 g?kg -1 ) intravenous immunoglobulins (IVIg). The efficacy of IVIg for reversing acute humoral rejection in renal and cardiac allograft recipients has been established [100]. IVIg have not been studied formally for the treatment of refractory acute rejection after LTx, but favourable outcomes have been seen occasionally and, compared with other treatment options, this therapy is largely nontoxic.…”