OR41 Potential role of non-hla antibodies in C4d negative and C4d positive antibody mediated rejections [AMR] following living/deceased donor renal transplantation

• Published in: Human immunology Vol. 79; p. 46
• Main Authors: Kanangat, Smriti, Kurbegovic-Skaljic, Ina, Cimbaluk, David, Oppermann, Maria, DeCresce, Robert
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2018
• DOI: 10.1016/j.humimm.2018.07.046
• ISSN: 0198-8859

To investigate the prevalence and potential immunological significance of antibodies reactive against non-HLA antigens in acute/chronic antibody mediated rejection/chronic rejection evidenced by histopathological findings. 19 Patients with biopsy proven C4d+ AMR; 37 with C4d- AMR, and 8 patients with T-cell mediated rejection [TCR] were tested for a panel of 39 non-HLA antibodies using a commercial Kit. The ability of these non-HLA antibodies to bind C1q was also done. The patients were scored positive for non-HLA antibodies based on a 95% cut off above the normal limits for each antibody in the general population. All patients had AMR with varying degrees of Interstitial Fibrosis and Tubular Necrosis. Majority of patients with C4d+ / C4d- AMR had more than 3 non-HLA antibodies [39 total targets] above 95% cut off. Most also had donor-specific HLA antibodies [DSA]. No specific pattern in terms of antibodies against structural proteins affecting cellular transformation, migration and fibrosis were observed. Notably, high levels of Glutathione S-Transferase tehta-1[GSTT1] antibodies with Acute Tubular Necrosis [ATN] was predominant in C4d- AMR cases [60%] while only 8% with C4d+ AMR patients with GSTT1 had ATN. Only 25% patients with TCR had Non-HLA antibodies and only towards two targets while almost 85-90% of AMR patients had multiple non-HLA antibodies. While non-HLA antigens like GSTT1 could be polymorphic and may induce allogenic response, many others could be against cryptic antigens exposed by injuries due to DSAs, or against altered self-antigens. Distinguishing immunological rejection from non-immunological injuries due to potential concurrent ATN and immunological injuries is challenging. The GSST1 antibodies detected were mostly C1q binding, but the mechanistic details of this finding is not clear now. The significance of this non-HLA Ab assay depends on more research into the genesis and predictive value of these pre-existing antibodies towards immunological rejection. Our current data tend to correlate with the concept of alloimmune mediated injuries leading to autoimmune responses based on concurrent HLA DSA and Non HLA antibodies. However AMR with no HA DSA and with non-HLA ab will be required for the de novo induction of non-HLA antibodies.