24-P

Abstract

To determine the HLA antibody of the isotype IgG and its subtypes (IgG1, IgG2, IgG3, and IgG4) in allosensitized patients and transplant recipients. Single Antigen Bead based assay using Luminex platform was done on diagnostic serum samples from 19 Renal/Heart Transplant candidates/recipients. Serum samples from 19 patients were analyzed, 4 had sequential samples, and 4 had pre and post transplant samples. The data from these limited samples indicate that while HLA antibodies are generally represented by all 4 subtypes of IgG, the predominant subtype was IgG1, (the efficient complement binding subtype) followed by IgG2. The physiological concentrations of IgG subtypes follows their designated numbers (IgG1 > IgG2 > IgG3 > IgG4), and seemingly, the alloimmune response also follows this pattern. There were notable differences in the antibody specificity profiles between pre and post transplant sera, but the distribution of IgG subtypes maintained the hierarchy in terms of number of IgG subtype specificities seen prior to transplantation except in one of the 4 patients tested where the pre-transplant IgG1 disappeared and serum from post transplant had IgG2 and IgG4 not present prior to transplant. Of the 4 sequential samples analyzed, HLA-specific antibody profile changed in all; however, the IgG subtype distribution pattern remained the same in all except for one patient where a shift from IgG1 and 2 to IgG3 was observed. The limited samples analyzed from allosensitized patients indicate a predominance of IgG1 subtype of HLA-Class I and II Specific antibodies based on the MFI values. However, IgG subtypes have different biological functions and the concentration alone might not indicate functional hierarchy. Detailed studies with more patients with pre and post transplant samples along with functional assays are required to better understand the role of alloimmune IgG isotypes in allograft function and survival.