Sera of non-alloimmunized individuals contain anti-HLA-I & -II IgG. Therefore it is reasonable expect HLA-I/-II reactivity of Intravenous Immunoglobulin (IVIg). However, the titers at which anti-HLA-I & -II IgG occur in IVIg preparations used to lower HLA IgG in pre- and post-transplant patients are not evaluated. Possibly this is the reason for failure of IVIg to lower anti-HLA IgG in sensitized patients. Also, high titers of anti-HLA-I/-II IgG in IVIg may place transplant patients at risk for endothelial damage as observed in patients and animal models of “IVIg-transfusion-related acute lung injury”.

Herein, we analyzed the commercial preparations of IVIg and sera of non-alloimmunized males & renal transplant patients for (1) HLA-Ia & Ib reactivity, (2) HLA-II reactivity, (3) IgG isotype characterization using Luminex®-based immunoassay. Reliability of secondary antibodies targeting H & L chains of IgG (One Lambda, Inc) and Fcγ2AB domain (S. Biochem) was examined for monitoring of anti-HLA IgG.

IVIg preparations and the purified-IgG and the native sera showed that HLA-IgG antibodies occur in the following order of frequency: DPA (80%), DQA (71%), DRB345 (67%), DQB (57%), Cw (50%), DBP (43%), DRB1 (21%), A (14%), and B (7%). Indeed, the therapeutic preparations of IVIg used for transplant patients had high titers of HLA-I/-II IgG, as follows: Gamastan = Gamunex < Octagam << Sandaglobulin. The highest titer of HLA-II IgG in different preparations of IVIg were observed against DRB3*03:01, DQA1*01:02DQB1*06:02 and DPA1*02:01/DPB1*23:01, exactly similar to that seen for the purified and native sera of all (n =15) healthy males. The anti-HLA IgG isotypes in IVIg, in purified and raw sera of non-alloimmunized males, as well as in allograft recipients differed in the following order:IgG1>IgG2a>IgG3>IgG4.

These results postulate the risks involved in transfusing IVIg for purpose of lowing HLA antibodies in sensitized patients and allograft recipients and stipulate reevaluating the use of IVIg in transplantation. If IVIg is used for transplantation, whether at low or high doses, the IVIg preparation should be assessed prior to use for the profile and titers of anti-HLA-I/-II IgG. Preferably the HLA-reactivity of IVIg should be examined in the context of molecular HLA typing of recipients and donors.

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