Background: It is known that detection of donor specific antibodies (DSA) is associated with antibody mediated rejection (AMR) and poor allograft outcomes. DSA mediates graft injury through complement dependent and complement independent mechanisms. Recognition of C4d negative AMR raised recent interests on complement independent mechanism of AMR. Fc gamma receptors (FcγR) are antibody receptors on monocytes, macrophages, and NK cells known to facilitate antibody dependent cell mediated cytotoxicity. Macrophage migration inhibitory factor (MIF) is multifunctional cytokine produced by innate immunity cells which can directly interact with DSA.

Purpose: This study aims to determine the association of FcγR and MIF gene polymorphisms with the detection of DSA in kidney allograft recipients.

Methods: 232 renal transplant patients between 2008 and 2012 at St. Vincent Medical Center were studied in a retrospective study design. DSAs were determined by Luminex technology. Single nucleotide polymorphisms of FcγRIIIa (rs396991), FcγRIIa (rs1801274) and MIF (rs1007888, rs755622) were determined by the real time PCR.

Results: Statistical differences were found in genetic polymorphisms of FcγRIIIa and MIF. The rs396991 (FcγRIIIa) alleles showed significant difference between DSA negative and positive groups (AA vs. CA, OR=1.828, p=0.045). This trend was maintained after 1 year of renal transplantation though it was not statistically significant (OR=1.883, p=0.057). Among this group, the detection of class II DSA was significantly associated with this allele (OR=2.331, p=0.019), but not with the class I DSA. The rs1007888 (MIF) alleles showed significant difference between DSA negative and positive groups (TT vs. CC, OR=2.204 p=0.042). Interestingly, statistical significances still found after 1 year of transplant (OR=2.745, p=0.023) and class I DSA showed statistical significance (OR=3.971 p=0.008). Other SNPs showed no significant association.

Conclusions: This study suggests that the presence of C allele of rs396991(FcγRIIIa) is associated with increased risk of DSA detection which may be more significant with class II DSA than class I DSA, and the presence of CC allele of rs1007888(MIF) is associated with increased risk of DSA detection of which trend is maintained after 1 year of transplantation and more specific in class I.

CITATION INFORMATION: Chang Y, Shah T, Min D. Association of Genetic Polymorphisms in Complement Independent Pathways with Donor Specific Antibodies in Kidney Allograft Recipients. Am J Transplant. 2016;16 (suppl 3).

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