Boussaïd Ismael, Bouhour Françoise, Vial Christophe, Caudie Christiane
Centre de biologie et pathologie Est, Service de neurobiologie, Groupement hospitalier Est, Lyon Bron.
Ann Biol Clin (Paris). 2011 Jul-Aug;69(4):476-80. doi: 10.1684/abc.2011.0603.
We reported the laboratory phenotype of a monoclonal IgM-lambda against disialylated gangliosides, in a 81-year-old man admitted to a neurological department because of the progressive development of distal paresthesias, gait unsteadiness, difficulty to walk and having falls. Serological studies revealed an IgM monoclonal protein with lambda light chain component of MGUS type. IgM level was 4 g/L. The positive laboratory studies showed high titers of IgM antibodies in excess of 1/10(5) against specific disialylated gangliosides including GD1b, GD3, GT1b and GQ1b. There was no serum IgM binding to MAG and SGPG/SGLPG. Clonality by in-house immunodot of ganglioside antibodies was demonstrated using kappa and lambda light chain specific antibodies. Light chain subtype of the anti-ganglioside antibody activity and monoclonal IgM was lambda subtype. The reactivity at high titers was against gangliosides containing the disialosyl epitope. The clinical and laboratory features have been described under the acronym CANOMAD: Chronic Ataxic Neuropathy with Ophthalmoplegia, M proteins, cold Agglutinins and Disialosyl antibodies. Administration of IVIg produced a significant neurological improvement during six years. Then the neuropathy became refractory in the IVIg and worsened in severity, a cure by Rituximab® was established. The patient died from a pneumopathy only two months later. Monoclonal IgM binding to disialylated gangliosides have high level of specificity for diagnosis of the CANOMAD syndrome.
我们报告了一名81岁男性的实验室表型，其存在一种针对双唾液酸化神经节苷脂的单克隆IgM-λ。该男性因进行性远端感觉异常、步态不稳、行走困难及跌倒而入住神经科。血清学研究显示存在一种具有MGUS型λ轻链成分的IgM单克隆蛋白。IgM水平为4g/L。阳性实验室检查显示，针对包括GD1b、GD3、GT1b和GQ1b在内的特定双唾液酸化神经节苷脂，IgM抗体滴度高，超过1/10(5)。血清IgM与MAG和SGPG/SGLPG无结合。使用κ和λ轻链特异性抗体通过内部免疫斑点法证实了神经节苷脂抗体的克隆性。抗神经节苷脂抗体活性和单克隆IgM的轻链亚型为λ亚型。高滴度反应针对含有双唾液酸表位的神经节苷脂。临床和实验室特征已根据首字母缩写CANOMAD进行描述：慢性共济失调性神经病伴眼肌麻痹、M蛋白、冷凝集素和双唾液酸抗体。静脉注射免疫球蛋白（IVIg）治疗在六年内使神经功能有显著改善。然后，该神经病对IVIg产生耐药，病情加重，使用利妥昔单抗®治愈。仅两个月后，患者死于肺病。与双唾液酸化神经节苷脂结合的单克隆IgM对CANOMAD综合征的诊断具有高度特异性。
