LRPAP1 自身抗体在套细胞淋巴瘤中与较好的预后相关。
LRPAP1 autoantibodies in mantle cell lymphoma are associated with superior outcome.
机构信息
Saarland University Medical School, José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Homburg/Saar, Germany.
Hôpital Necker, Institut Imagine, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Paris, France.
出版信息
Blood. 2021 Jun 10;137(23):3251-3258. doi: 10.1182/blood.2020008835.
Low-density lipoprotein (LDL) receptor-related protein-associated protein 1 (LRPAP1) had been identified by B-cell receptor (BCR) expression cloning and subsequent protein array screening as a frequent and proliferation-inducing autoantigen of mantle cell lymphoma (MCL). 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 immunoglobulin G (IgG) class and were clonally light chain restricted (27 with κ light chains, 14 patients with λ light chains). Titers ranged between 1:400 and 1:3200. The presence of LRPAP1 autoantibodies was not significantly associated with any baseline clinical characteristic, however, it was associated with a superior 5-year probability for failure-free survival (FFS) of 70% (95% confidence interval [CI], 57% to 87%) vs 51% (95% CI, 44% to 58%), P = .0052; and for overall survival (OS) of 93% (95% CI, 85% to 100%) vs 68% (95% CI, 62% to 74%), P = .0142. LRPAP1-seropositive patients had a Mantle Cell Lymphoma International Prognostic Index-adjusted hazard ratio for FFS of 0.48 (95% CI 0.27-0.83, P = .0083) and for OS of 0.47 (95% CI 0.24-0.94, P = .032). LRPAP1 autoantibodies were frequently detected in a large cohort of MCL patients treated within prospective multicenter clinical trials. Our results suggest better outcomes for LRPAP1-autoantibody seropositive patients.
低密度脂蛋白（LDL）受体相关蛋白相关蛋白 1（LRPAP1）已通过 B 细胞受体（BCR）表达克隆和随后的蛋白质阵列筛选被鉴定为套细胞淋巴瘤（MCL）的常见增殖诱导自身抗原。有趣的是，在 28 例 MCL 患者中检测到 8 例高滴度和轻链受限的 LRPAP1 自身抗体。在本研究中，对欧洲 MCL 网络年轻和老年试验中治疗的患者的血清中的 LRPAP1 自身抗体进行了频率、与疾病特征的关联以及预后影响的分析。在 312 例可评估的 MCL 患者中有 41 例（13％）检测到 LRPAP1 自身抗体。这些 LRPAP1 自身抗体主要属于免疫球蛋白 G（IgG）类，并且克隆性轻链受限（27 例κ轻链，14 例λ轻链）。滴度范围为 1:400 至 1:3200。LRPAP1 自身抗体的存在与任何基线临床特征均无明显关联，但是与 5 年无失败生存（FFS）的概率较高相关，分别为 70％（95％CI，57％至 87％）和 51％（95％CI，44％至 58％），P =.0052；以及总生存（OS）的 93％（95％CI，85％至 100％）和 68％（95％CI，62％至 74％），P =.0142。LRPAP1 阳性患者的无失败生存风险比（FFS）调整后的 HR 为 0.48（95％CI 0.27-0.83，P =.0083），OS 为 0.47（95％CI 0.24-0.94，P =.032）。在大型前瞻性多中心临床试验中治疗的 MCL 患者中经常检测到 LRPAP1 自身抗体。我们的结果表明，LRPAP1 自身抗体阳性患者的预后更好。
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