Solid phase assays, particularly single-antigen beads, have substantially increased the sensitivity and accuracy of antibody detection in transplantation. However, donor specific antibodies(DSA) against human leukocyte antigens(HLA) are not always detectable in cases consistent with antibody mediated injury. We hypothesized that in these cases, antibodies against non-HLA antigens may be associated with the graft injury process. Non-HLA antibodies may be contributory to allograft injury even in cases with detectable DSA, possibly accounting for the heterogeneity of antibody mediated rejection and development of transplant glomerulopathy.

Retrospectively, we reviewed all kidney transplant biopsies performed at our center in the 1/1/2005 and 5/31/2015 interval and identified patients that had concomitant serum testing for DSA. We identified 36 patients that had no detectable DSA but had histological changes consistent with AMR (sAMR group) and 44 patients that had no histological changes of rejection and no detectable DSA(C group). The same serum samples used for DSA evaluation were analyzed using a group of 62 single antigen beads by Luminex for the presence of non-HLA antibodies chosen for their role in autoimmunity and transplantation. Additionally, we performed similar analyses for 71 patients with AMR on biopsy and detectable DSA and 19 health controls(data not included).

A group of 56 non-HLA antibodies were included in analysis after excluding 6 due to high correlation with negative controls(R>.9). We excluded 4 patients from sAMR group and 2 from C group due to outlier values of their negative controls. Logistic regression models were constructed for each individual non-HLA antibody as predictor, adjusted for negative control values and data is presented as forest plot depicting OR and 95%CI comparing sAMR with the C group.Conclusion: Despite the lack of statistical significance, impacted by the sample size, this exploratory analysis identifies multiple potential targets for future analysis.

CITATION INFORMATION: Leca N, Gimferrer I, Warner P, Nelson K, Bakthavatsalam R, Sibulesy L, Najafian B, Robinson-Cohen C, Kestenbaum B. Association of Non-HLA Antibodies with Histological Changes of Antibody Mediated Injury in Kidney Transplantation. Am J Transplant. 2017;17 (suppl 3).

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