Bosseboeuf Adrien, Mennesson Nicolas, Allain-Maillet Sophie, Tallet Anne, Piver Eric, Decaux Olivier, Moreau Caroline, Moreau Philippe, Lehours Philippe, Mégraud Francis, Salle Valéry, Bigot-Corbel Edith, Harb Jean, Hermouet Sylvie
Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Inserm, Université de Nantes, Université d'Angers, 44000 Nantes, France.
Laboratoire de Biochimie, Centre Hospitalier Universitaire (CHU) Tours, 37000 Tours, France.
Cancers (Basel). 2020 May 15;12(5):1254. doi: 10.3390/cancers12051254.
Chronic stimulation by infectious or self-antigens initiates subsets of monoclonal gammopathies of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). Recently, glucosylsphingosine (GlcSph) was reported to be the target of one third of monoclonal immunoglobulins (Igs). In this study of 233 patients (137 MGUS, 6 SMM, 90 MM), we analyzed the GlcSph-reactivity of monoclonal Igs and non-clonal Igs. The presence of GlcSph-reactive Igs in serum was unexpectedly frequent, detected for 103/233 (44.2%) patients. However, GlcSph was targeted by the patient's monoclonal Ig for only 37 patients (15.9%); for other patients (44 MGUS, 22 MM), the GlcSph-reactive Igs were non-clonal. Then, the characteristics of patients were examined: compared to MM with an Epstein-Barr virus EBNA-1-reactive monoclonal Ig, MM patients with a GlcSph-reactive monoclonal Ig had a mild presentation. The inflammation profiles of patients were similar except for moderately elevated levels of 4 cytokines for patients with GlcSph-reactive Igs. In summary, our study highlights the importance of analyzing clonal Igs separately from non-clonal Igs and shows that, if autoimmune responses to GlcSph are frequent in MGUS/SMM and MM, GlcSph presumably represents the initial pathogenic event for ~16% cases. Importantly, GlcSph-initiated MM appears to be a mild form of MM disease.
传染性抗原或自身抗原的慢性刺激引发了意义未明的单克隆丙种球蛋白病（MGUS）、冒烟型多发性骨髓瘤（SMM）或多发性骨髓瘤（MM）的不同亚型。最近，据报道葡萄糖神经酰胺（GlcSph）是三分之一单克隆免疫球蛋白（Ig）的靶点。在这项对233例患者（137例MGUS、6例SMM、90例MM）的研究中，我们分析了单克隆Ig和非克隆Ig的GlcSph反应性。血清中存在GlcSph反应性Ig的情况出人意料地常见，在103/233（44.2%）例患者中检测到。然而，只有37例患者（15.9%）的单克隆Ig靶向GlcSph；对于其他患者（44例MGUS、22例MM），GlcSph反应性Ig是非克隆性的。然后，我们检查了患者的特征：与具有爱泼斯坦-巴尔病毒EBNA-1反应性单克隆Ig的MM患者相比，具有GlcSph反应性单克隆Ig的MM患者临床表现较轻。除了GlcSph反应性Ig患者的4种细胞因子水平中度升高外，患者的炎症谱相似。总之，我们的研究强调了将克隆性Ig与非克隆性Ig分开分析的重要性，并表明，如果MGUS/SMM和MM中对GlcSph的自身免疫反应频繁，那么GlcSph可能代表了约16%病例的初始致病事件。重要的是，由GlcSph引发的MM似乎是MM疾病的一种轻度形式。
