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Thurner, Lorenz; Fadle, Natalie; Bittenbring, Jörg Thomas; Regitz, Evi; Schuck, Rita; Cetin, Onur; Stuhr, Arianne; Rixecker, Torben; Murawski, Niels M.; Poeschel, Viola; Kaddu-Mulindwa, Dominic; Preuss, Klaus Dieter; Stilgenbauer, Stephan; Hermine, Olivier; Kluin-Nelemans, Jc C.; Hartmann, Sylvia; Dreyling, Martin; Pott, Christiane; Bewarder, Moritz; Hoster, Eva (2021): LRPAP1-autoantibodies in mantle cell lymphoma are associated with superior outcome. In: Blood
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Abstract

Recently, we identified LDL receptor related protein associated protein 1 (LRPAP1) as frequent autoantigen of recombinant B-cell receptors (BCRs) of mantle cell lymphoma (MCL). This autoantigen induced proliferation in two cell lines with BCR-reactivity against LRPAP1. Of interest, high-titered and light-chain-restricted LRPAP1-autoantibodies were detected in 8 of 28 patients with MCL. In the present study, LRPAP1-autoantibodies in sera of patients treated within the Younger and Elderly trials of the European MCL Network were analyzed regarding frequency, association with disease characteristics and prognostic impact. LRPAP1-autoantibodies were detected in 41 (13 %) of 312 evaluable patients with MCL. These LRPAP1-autoantibodies belonged predominantly to the IgG class (IgG: 37; IgM: 4, IgG-subclasses: IgG1: 25, IgG2: 7, IgG3: 4 and IgG4: 1) and were clonally light-chain-restricted (27 with kappa light-chains, 14 patients with lambda light-chains). Titers ranged between 1:400 up to 1:3200. The presence of LRPAP1-autoantibodies was not significantly associated with any baseline clinical characteristic. However, the presence of LRPAP1-autoantibodies was associated with a superior 5-year probability for failure-free survival (FFS) of 70% (95% CI: 57%-87%) vs. 51% (95% CI: 44%-58%) p:0.0052; and for overall survival (OS) of 93% (95% CI: 85%-100%) vs. 68% (95% CI 62%-74%), p=0.0142. LRPAP1-seronegative patients had a MIPI-adjusted HR for FFS of 2.1 (95% CI 1.2-3.6, p=0.0083) and for OS of 2.1 (95% CI 1.07-4.2, p=0.032). LRPAP1-autoantibodies were frequently detected in serum samples of a large cohort of MCL patients treated within prospective multicenter clinical trials. Our results suggest better outcomes for LRPAP1-autoantibody seropositive patients.