PURPOSE: BK virus nephropathy, alloimmunity and autoimmune disease are important complications after kidney transplantation. We recently demonstrated that antibodies to kidney transplant-associated self-antigens (TSA) such as collagen type IV (COL4) and fibronectin (FN) are associated with transplant glomerulopathy, a form of chronic rejection contributing to allograft failure. Whether these are present in the early post-transplant period is unknown. We tested the hypothesis that early BK viremia, a biomarker of alloimmune over-immunosuppression, is associated with autoimmune responses against the allograft that could explain the paradox of simultaneous BK infection and nephropathy.
METHODS: We interrogated plasma samples collected prospectively from kidney transplant recipients in a BK virus monitoring study (n=19). Subjects were monitored serially for the presence of BK viruria and/or BK viremia during year 1 post-transplant. Using ELISA, we measured circulating levels of COL4- and FN-TSA at 1-year post-transplant in subjects who developed BK viremia (BK-viremic, n=9). The comparator group was subjects without BK viremia or viruria (BK-neg, n=10) during year 1 post-transplant. Subjects were considered positive for COL4- and/or FN-TSA if plasma levels exceeded a cutoff value of 2 standard deviations above the mean from healthy control subjects.
RESULTS: 9/9 (100%) BK-viremic were positive for COL4-TSA at 1-year post-transplant, vs. 5/10 (50%) in BK-neg (p=0.03). The median plasma level of COL4-TSA was significantly higher in BK-viremic vs. BK-neg [1411 (808-2234) vs. 764 (176-1279) ng/mL, p=0.007]. There was a similar trend for FN-TSA: 7/9 (78%) in BK-viremic vs. 5/10 (50%) in BK-neg were positive at 1-year post-transplant (p=0.3). The median plasma level of FN-TSA was significantly higher in BK-viremic vs. BK-neg [475 (0-849) vs. 85 (0-489) ng/mL, p=0.04].
CONCLUSIONS: Antibodies to kidney transplant-associated self-antigens COL4 and FN are prevalent in the early post-transplant period. Early BK viremia, a biomarker of alloimmune over-immunosuppression, is associated with increased transplant-associated autoimmunity, a phenomenon that is associated with chronic rejection. This may explain the paradox of concomitant BK viral infection and rejection or allograft dysfunction.
To cite this abstract in AMA style:Seifert M, Klein C, Brennan D, Mohanakumar T. Early BK Viremia Is Associated with Antibodies to Kidney Transplant-Associated Self-Antigens Collagen Type IV and Fibronectin [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/early-bk-viremia-is-associated-with-antibodies-to-kidney-transplant-associated-self-antigens-collagen-type-iv-and-fibronectin/. Accessed October 24, 2020.
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