Buxbaum J
Medical Service, New York Department of Veterans Affairs Medical Center, New York.
Hematol Oncol Clin North Am. 1992 Apr;6(2):323-46.
All forms of MIDD are related to the presence of an expanded clone of B-cell origin that is producing an Ig product, usually, but not exclusively an L-chain, which is predisposed to deposit in tissues, with or without some degree of processing. The nature of the processing is currently unclear, although limited proteolysis is likely to play a major role in most, but not all, patients. Diagnosis is made by the identification, using immunohistochemical techniques, of the monoclonal Ig nature of the deposited material, which may be fibrillar and Congo red-positive (AL and AH), or more amorphous and Congo red-negative (LCDD and LCHDD). Present modalities of therapy are similar or identical to those employed in multiple myeloma, attempting to eliminate the monoclonal cell population responsible for the production of the precursor of the deposited protein. A variety of ancillary therapeutic measures may be employed to treat problems associated with the failure of specific organs produced by the deposition. The details of how the uniformly soluble precursor molecule is converted to an essentially insoluble aggregate that compromises the function of the tissue in which it is formed are not yet known. It is still not possible to construct a potential "unified field theory" governing the deposition of intact Igs or their fragments. It is likely, as appears to be the case in other forms of amyloid unrelated to Ig, that many proteins contain, within their sequence, peptides that are capable of forming insoluble beta sheet-like structures. When these peptides are isolated from their surrounding molecular environment--either by proteolysis in the test tube, by a mutational change that predisposes them to limited proteolysis; or by a point mutation, deletion, or some other structural modification (as glycosylation), which alters their molecular context without proteolysis--and are present in sufficient concentration, they become less soluble under physiologic conditions. It is likely that the site of deposition depends upon the site of synthesis, but to a lesser extent than the protease profile and the physicochemical make-up of the affected tissues. Better understanding of the latter factors is necessary for the development of better modes of treatment.
所有形式的单克隆免疫球蛋白沉积病（MIDD）都与源自B细胞的扩增克隆的存在有关，该克隆产生一种免疫球蛋白产物，通常但并非仅为轻链，其易于在组织中沉积，无论是否经过一定程度的加工。目前尚不清楚加工的性质，尽管有限的蛋白水解在大多数（但不是所有）患者中可能起主要作用。诊断是通过免疫组织化学技术鉴定沉积物质的单克隆免疫球蛋白性质来进行的，沉积物质可能是纤维状且刚果红阳性（AL和AH），或更无定形且刚果红阴性（LCDD和LCHDD）。目前的治疗方式与多发性骨髓瘤中使用的方式相似或相同，试图消除负责产生沉积蛋白前体的单克隆细胞群体。可以采用多种辅助治疗措施来治疗与沉积导致的特定器官功能衰竭相关的问题。目前尚不清楚均匀可溶的前体分子如何转化为基本上不溶的聚集体，从而损害其形成组织的功能。目前仍无法构建一个潜在的“统一场论”来解释完整免疫球蛋白或其片段的沉积。与其他与免疫球蛋白无关的淀粉样变形式一样，许多蛋白质可能在其序列中包含能够形成不溶性β折叠样结构的肽段。当这些肽段从其周围的分子环境中分离出来时——无论是通过试管中的蛋白水解、使其易于有限蛋白水解的突变变化；还是通过点突变、缺失或其他一些结构修饰（如糖基化），在不进行蛋白水解的情况下改变其分子环境——并且浓度足够时，它们在生理条件下的溶解度会降低。沉积部位可能取决于合成部位，但程度小于受影响组织的蛋白酶谱和物理化学组成。更好地了解后两个因素对于开发更好的治疗方式是必要的。
