Background: The presence of preformed donor-specific antibody (pDSA) in HS pts and development of de-novo DSA (dnDSA) in NS patients are risk factors for ABMR. However, they produce different ABMR profiles, Type I and II, respectively, with varying impact severity. The effects of pDSA vs. dnDSA were compared in pediatric kidney transplant recipients.

Methods: 16 pts with biopsy-proven ABMR were evaluated for DSA using single antigen beads, at transplant, at rejection, and at follow up. DSA was considered strong if MFI>10,000. DSA with highest MFI was termed Immunodominant DSA. Allograft biopsies were scored according to Banff criteria. Presence of viral infection and medication non-adherence were evaluated.

Results: 7/16 (44%) who developed ABMR were HS at transplant, while 9 (56%) patients were NS and developed dnDSA. 7 HS patients (5/7 with pDSA) developed type I ABMR while all 9 (100%) NS pts developed dnDSA and type II ABMR (p<0.001). HS patients developed ABMR earlier (median, IQR= 63, 41-406 days vs 1344, 1179-2966 days, p=0.017). There was no difference in serum Cr at the time of biopsy between the groups . Strong Class II immunodominant DSA was present in 9(100%) of NS patients and 2/7 (28%) of HS patients (p= 0.0093). 3/7 (42%) had class I DSA, 2/7 (28%) had both Class I and II. NS patients were likely to have viral infection or non-adherence (88.8% vs 14.3%, p<0.001) preceding detection of DSA and ABMR. Pathology showed HS pts had worse transplant glomerulitis (g-score 1.57±0.98 vs 0.56±0.73, p=0.031); however, NS had more C4d+ ABMR (C4d score 2.89±0.33 vs. 1.43±1.51, p=0.013). There was no difference in rates of concomitant cell mediated rejection between groups. NS patients had fewer episodes of graft loss (11.1% vs 42.8%), although not significant (p=0.2).

Conclusions: HS pts are more likely to develop Type I ABMR early post transplant with higher incidence of graft loss. NS pts with dsDSA develop Type II ABMR years after transplant and have immunodominant Class II DSA; these pts are likely to have been under reduced immunosuppression due to viral infections or non-adherence. Careful screening for ABMR in HS patients with pDSA is warranted. Likewise, screening for dnDSA in NS pts, especially after viral infection or non-adherence, could lead to early intervention and potentially better outcome.

CITATION INFORMATION: Steggerda J, Kim I, Haas M, Zhang X, Wang A, Pizzo H, Kamil E, Jordan S, Puliyanda D. Clinical and Histopathologic Features of Antibody Mediated Rejection (ABMR) in Highly Sensitized (HS) vs Non-Sensitized (NS) Pediatric Renal Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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