Immunoglobulin A Isotype Anti-HLA Antibodies and Graft Survival in Kidney Transplanted Patients

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Abstract
IgA isotype antibodies (Ab) against human leukocyte antigens (HLA) recognize their target with high affinity as well as high avidity. Little is known about the influence of these IgA isotype Abs on organ graft survival after transplantation (Tx). For this study, sera from 276 kidney re-Tx candidates were selected who lost their transplanted organ in the past, and were listed on the waitlist of Erlangen/Nuremberg for a second Tx. The time to first dialysis after Tx (TtD), median, measured in months, was used as a precise endpoint marker for loss of graft function. IgG and IgA Abs were investigated using Luminex technology on generic (Luminex mixed test) and Ab specification (Luminex Single Antigen test) level. Of the 276 sera, 89 were tested positive for IgA and 243 for IgG Abs. Interestingly, within 86/89 sera, the presence of IgA Ab was significantly linked to the presence of IgG (p < 0.0001). As expected, stratification by IgA and IgG status revealed the longest median graft survival in IgA/IgG double negative patients (TtD 127 months). Patients tested positive exclusively for IgG Abs displayed intermediate graft survival (TtD 116 months) whereas, IgA/IgG double positive patients had a significantly reduced median graft survival compared to any other subgroup (TtD 88 months, p < 0.001). Only three patients showed exclusively IgA Abs and were not possible to analyze statistically. In our previous study with 694 patients, we showed, that the presence of donor specific IgA (IgA-DSA) Abs correlated with a significant worse outcome (TtD 76 months) compared to IgA positive patients without showing IgA-DSA (TtD 82 months). The presence of serum anti-HLA-IgA Abs in conjunction with IgG Abs marks a high risk subgroup in kidney Tx patients with a significantly reduced graft survival compared to patients displaying exclusively IgG Abs. This influence of IgA may indicate a novel functional contribution for improved risk stratification in the post and potentially pre transplantation monitoring.

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