Introduction.In a recent study (AJT,2011;11:2405), eculizumab decreased the incidence of early antibody mediated rejection(AMR) after +XMKTx. Post-transplant plasma exchange (PE) was not routinely used thus allowing DSA levels to follow their natural history. The aim of the current study was to perform a detailed study of DSA after +XMKTx and how this correlates with graft histology.
Methods. Using the single antigen bead (LABscreen) assay, we determined IgG alloantibody specificities and levels (as measured by the mean fluorescence intensity (MFI)) in 31 patients who underwent +XMKTx and treated with eculizumab. 23 of these did not receive post-transplant PE and 8 did undergo PE within one year (1 per routine early in the experience, 2 for early AMR, and 5 for persistently high DSA levels >1month after +XMKTx). DSA levels at 1yr were compared to baseline (BL) levels (paired t-test) and correlated to histology (Cg>0, C4d>0, PTC>1) on 1yr protocol biopsies (Fishers exact test).
Results.At BL, 78 different DSA specificities (41 Class1 and 37 Class2) were identified in the 31 patients. By 1yr, 15 new DSA specificities developed (4 class 1 and 11 Class2). The Mean±SD MFI of total DSA at BL was 4318±4462 (3823±4174 Class1 and 4984±4746 Class2) which at one year decreased to 1994±3519, p<0.0001(766±1351 Class1,p<0.001 and 3396±4583 Class2,p=0.0241). Importantly, at 1yr, changes in DSA were quite variable: 44% of specificities had total disappearance (MFI=0), 10% had near total disappearance (MFI<1000), 19% had significant decrease (MFI <0.5xBL) and 15% had significant increase (MFI>1.5xBL). 13% were between 0.5 and 1.5xBL (No change).
When compared to patients with DSA MFI >1000 at 1yr, patients with DSA MFI<1000 had a lower rate of transplant glomerulopathy (TG) (0%, 0/12, vs 42.1%, 8/19, p=0.012). C4d deposition (16.7% vs 42.1%, p=0.24) and PTCitis (33.3% vs 68.4%, p=0.07) were similar. Importantly, no patient with DSA MFI < 1000 received post-tx PE.
Conclusion. Changes in DSA levels vary widely after +XMKTx and may decrease to low levels at 1yr without PE. Patients with low DSA levels at 1yr have decreased incidence of TG, yet some demonstrate C4d deposition and PTCitis suggesting these processes may be due to subtypes other than IgG or antibody independent mechanism of graft injury.
Stegall, M.: Grant/Research Support, Alexion, Millennium.
To cite this abstract in AMA style:Raghavaiah S, Gandhi M, Cornell L, Kremers W, Dean P, Taner T, Stegall M. “Spontaneous” Reduction in Donor Specific Allo-Antibody (DSA) after Positive Cross Match Kidney Transplantation (+XMKTx) Is Associated with Improved Histology [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/spontaneous-reduction-in-donor-specific-allo-antibody-dsa-after-positive-cross-match-kidney-transplantation-xmktx-is-associated-with-improved-histology/. Accessed May 26, 2017.
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