Steck A J, Kuntzer T
Service de Neurologie, Hôpital Cantonal Universitaire, Bâle, Suisse, France.
Rev Neurol (Paris). 2002 Oct;158(10 Pt 1):971-8.
Disturbancies in neurological functions associated with paraproteinaemic states are well documented. In recent years increasing attention has been given to paraproteinemia in the absence of evidence of malignancy. In this article we review the main clinical and pathological features associated with IgM paraproteins. Neurological complications affecting the central nervous system are rare, while peripheral neuropathies are frequently observed. Recent advances at the histological and molecular level have allowed a better characterization of clinical syndromes and have given new insights into their pathogenesis. The most convincing evidence for a causal relationship can be drawn from IgM monoclonal gammopathies with specificities directed against carbohydrate determinants of the myelin associated glycoprotein (MAG). There remain, however, many unresolved questions such as how monoclonal anti-MAG IgM antibodies cross the blood-nerve barrier and trigger a chronic demyelinating polyneuropathy while the central nervous system is essentially spared. Current immune therapies for neuropathy associated with IgM paraproteins are temporarily effective in half of patients and are often associated with considerable side effects which limit their prolonged use and efficacy. The availability of safer therapies such as humanized monoclonal antibodies that eliminate specifically B-cell and B-cell precursors may open a new avenue for the management of these patients.
与副蛋白血症相关的神经功能障碍已有充分记录。近年来，人们越来越关注无恶性肿瘤证据的副蛋白血症。在本文中，我们回顾了与IgM副蛋白相关的主要临床和病理特征。影响中枢神经系统的神经并发症罕见，而周围神经病变则较为常见。组织学和分子水平的最新进展使我们能够更好地描述临床综合征，并对其发病机制有了新的认识。最有说服力的因果关系证据来自针对髓鞘相关糖蛋白（MAG）碳水化合物决定簇具有特异性的IgM单克隆丙种球蛋白病。然而，仍有许多未解决的问题，例如单克隆抗MAG IgM抗体如何穿过血神经屏障并引发慢性脱髓鞘性多发性神经病，而中枢神经系统基本不受影响。目前用于治疗与IgM副蛋白相关神经病变的免疫疗法在一半的患者中暂时有效，且常常伴有相当多的副作用，这限制了其长期使用和疗效。更安全的疗法如能特异性清除B细胞和B细胞前体的人源化单克隆抗体的出现，可能为这些患者的治疗开辟一条新途径。
