Development of De Novo HLA antibodies after transplantation: Results from the CTOT02 Study.

CTOT02 is a large prospective multi-center trial set in 2 phases. Phase 1 involved screening of unsensitized patients 3-36 months post transplant every 3 months for the development of anti-HLA antibodies with a follow-up period of 60 months. Dr. Chandraker from Brigham presented the results of the first phase of the study. Below are a few key findings.

Out of 653 patients screened, 12% developed de novo HLA-antibodies. Importantly, the data was on any de novo HLA-antibody – not donor specific HLA antibody.

21.5% had antibody to class I, 64% to class II, and 13.9% to both class I and II HLA antibodies.

Risk factors for developing HLA antibodies were
– Younger age recipient
– More HLA mismatches

The use of IL-2 inhibitors (basiliximab) for induction was found to be protective compared to either antithymocyte globulin or alemtuzumab. More on this surprise later.

Acute rejection was more likely to occur after the development of antibodies. In fact, 22% had a rejection episode before while 78% had a rejection episode after the development of HLA antibody.

Complement fixing antibodies were more likely to be present in patients with both class I and class II HLA antibodies and were more likely to be donor specific.

Development of HLA antibodies did not portray worse graft survival.

There were a couple of big surprises here. First that IL-2 inhibitor induction had a protective effect on the development of HLA antibodies. As many of the audience members mentioned, it is impossible to be sure that this was not due to selection bias at the time of transplant. In general, most centers reserve IL-2 inhibitors to lower risk transplants. In fact, another abstract in the same session actually revealed the opposite finding. Development of antibodies before rejection was counterintuitive as the current dogma is that antibodies form after a rejection episode. Finally, it’s surprising that patients who developed HLA antibodies did not have worse graft survival, albeit longer follow up may change this finding. Fascinating data, however, I would have liked to hear a little more about the patients who developed donor specific HLA antibodies and the outcomes of those who had a rejection.

Post written by Dr. Vinay Nair, eAJKD Advisory Board member.

Check out all of eAJKD’s coverage of the 2013 American Transplant Congress.