P027Potential influence of bacterial infections in augmented HLA-C antibody responses with consistent cross match positivity

Abstract

A patient listed for renal transplant had consistent positive cross matches with several sequential donors over a period of time when there are no DSAs that were listed as Unacceptable Antigens [UAs]. The listed patient had several Class I antibodies especially towards HLA-C antigens during the entire monitoring period. But none of them matched the criteria of ⩾ 5000 MFI which we use for all patients as a cut off value unacceptable C antigens [UAs]. From September 2017 the patient got several offer till 01/22/2018 and all B cell Flow cross matches were decisively positive. The DSAs were all directed towards HLA-C antigens except on two occasions where HLA-B 8 and or A33 DSAs were also seen along with one or more HLA-C DSAs. Upon investigation of the antibody specificity trend, the following pattern for HLA C antibodies indicating a significant spike around between 05/04/2017 and 01/09/2018 was observed. The arrow where there is a dip shows that none of them were C1q binding. The patient complained about a potential infection of chest catheter on 09/26/2017 through telephonic encounter with nurse practioner with no fever but noted redness around the site. According to the patient, this is how his prior infections started indicating previous infections as well. Later the patient developed foot ulcer which was not notified but found out during the investigation of spike in HLA antibodies after repeated positive cross matches with several deceased donors. Bacteriological investigation of the foot ulcer revealed presence of two species of Staphylococcus by MALDI-TOF method which was eventually treated with appropriate antibiotics and got resolved. It is a long recognized fact that several bacterial antigens shares amino acid sequences with various HLA-Loci. It is known that infections and immunizations can induce polyclonal B cell activation resulting in increased HLA antibody responses in previously sensitized patients. This case signifies the importance of non-conventional ways of HLA antibody boosting and importance of antibody profiling following any infections. Had we known about the infections we could have periodically monitored the antibody profile of the patient and avoided some of the crossmatches by entering unacceptable C antigens.