Course of donor specific anti-HLA antibodies after induction therapy with rituximab in renal transplantation


M.C. Baas, W.A. Allebes, M.W.F. van den Hoogen, I. Joosten, L.B. Hilbrands

Chair(s): Prof. dr. L.B. Hilbrands & dr. H.M. Kwakkel-van Erp

Wednesday 8 march 2017

17:42 - 17:54h at Willem Pijperzaal

Categories: Parallel - Klinisch

Parallel session: Parallelsessie VI - Klinisch 1 - HLA-antilichamen en immunomodulatie


The presence of pre-existing or de novo donor-specific antibodies against HLA (DSA), is associated with a worse graft outcome after renal transplantation.  B-cell depletion protocols have shown to reduce DSA and chronic antibody mediated rejection. We aimed to study the effects of rituximab as a single-agent induction therapy  on the titers of pre-existent or de novo DSA after renal transplantation and relate this to rejection free and overall graft survival.

We collected sera in participants of a prospective double-blind randomized study on the efficacy and safety of the prophylactic use of rituximab, added to standard immunosuppressive treatment (prednisolone, tacrolimus and mycophenolate mofetil) in comparison with standard immunosuppressive treatment alone in renal transplantation (www.clinicaltrials.gov, NCT00565331). 280 patients were included in this trial (142 received placebo, 138 rituximab). Serum before transplantation and at 12 months after transplantation was available in 127 placebo and 119 rituximab treated patients (total 246 patients).

At the moment of transplantation, 12.6% of placebo- and 8.4% of rituximab treated patients had anti-HLA class 1 antibodies. Pre-existent class 1 DSA were present in 7/127 (5.5%) placebo- and 5/119 (4.2%) rituximab treated patients (NS). In both groups all class 1 DSA disappeared at month 12 after transplantation.

Anti-HLA class 2 antibodies were present in 9.4% of placebo- and 8.4% of rituximab treated patients at the time of transplantation. Pre-existent class 2 DSA were present in 6/127 (4.7%) placebo- and 1/119 (0.8%) rituximab treated patients (NS). In the placebo group, class 2 DSA disappeared in 3 patients and persisted in the other 3. Class 2 DSA persisted in the patient treated with rituximab

2/127 (1.6%) placebo- and 2/119 (1.7%) rituximab treated patients developed de novo class 1 DSA (NS).

De novo class 2 DSA developed in 7/127 (5.5%) placebo-treated patients at 12 months and in only 1 patient treated with rituximab (0.8%, p = 0.04).

In conclusion, pre-existent class 1 DSA disappeared at 12 months after transplantation independent of rituximab induction therapy. Pre-existent class 2 DSA are less likely to disappear. Although only very few patients developed de novo DSA, rituximab induction therapy might inhibit the formation of de novo class 2 DSA.