A clinical research consortium sponsored by NIAID
Feng S, Philogene M, Phippard D, Punch J, Reyes J, Levitsky J Klintmalm G, Zimmerman M, Sayre P, DesMarais M, Kopetskie H, Shaked A
University of California, San Francisco, San Francisco, CA, University of Michigan, Ann Arbor, MI, University of Washington, Seattle, WA, Northwestern University, Chicago, IL, Baylor, Dallas, TX, University of Colorado, Aurora, CO, Immune Tolerance Network, Bethesda, MD Rho Federal Systems Division, Chapel Hill, NC University of Pennsylvania, Philadelphia, PA
ABSTRACT
BACKGROUND: ITN030ST is an ongoing, prospective, multicenter study of recipients with hepatitis C (HCV) or nonimmune nonviral etiologies. 67 subjects (33 HCV) were randomized to IS withdrawal (53; 26 HCV) or IS maintenance (14; 7 HCV) 1-2 years after transplantation. At randomization, the mean (SD) total daily tacrolimus dose was 4.3 (1.6) mg; 12 hour trough was 7.1 (3.1) ng/mL. We describe here DSA evolution with IS withdrawal.
METHODS: DNA sequencing was used for HLA typing. HLA A, B, C, DR and DQ antigen mismatch was evaluated. The LABScreen® Single Antigen™ assay determined HLA antibody specificity. Alloantibodies were monitored 8, 24, 40 and 56 weeks post randomization, corresponding to 100% (BID to QD dosing), 50%, 12.5% and 3.6% of baseline IS.
RESULTS: 39 (20 HCV) of 67 (33 HCV) subjects comprised the study group; 34 in the IS withdrawal group and 5 in the IS maintenance group. Degree of mismatch did not differ among groups. Only 1/39 had DSA at randomization. DSA developed in 2/2 tolerant subjects (stable liver tests ≥17 months without IS). 0/5 maintenance subjects had detectible DSA. DSA developed in 6/17 non-tolerant (biopsy proven acute rejection) and 2/15 clinically failed (failed withdrawal with increased liver tests, without biopsy proven acute rejection) subjects. Notably, all DSAs had HLA-Class II specificity.
CONCLUSIONS: IS withdrawal was associated with DSA development against HLA Class II antigens. DSA development was not prohibitive of operational tolerance. DSA was more frequently observed at ≤ 50% of baseline IS among non-tolerant than clinically-failed subjects. The clinical and histologic importance of DSA requires analysis of more subjects with longer follow-up.
