Biology and therapy of immunoglobulin deposition diseases

Abstract

All forms of MIDD represent pathologic deposition of immunoglobulin as amorphous casts, crystals, congophilic fibrils (in AL amyloid), or punctate noncongophilic deposits (in LCDD/HCDD/LHCDD). Diagnosis is based on identification and immunohistochemical characterization of deposits and Congo red staining. Current information including development of novel in vitro and in vivo models suggests a contributory role of both protein and host factors in the pathogenesis of these disorders. In particular, primary structural features of the VL portions of the light chain molecule may affect not only the extent but also the morphologic type of protein deposits. Thus, certain types of light chains may be particularly pathogenic, although the nature or extent of proteolysis/processing involved in the pathogenesis of these deposits is yet unclear. Recent data also point to the importance of accessory molecules, cytokines, and host factors in this process. Newer therapeutic approaches using high-dose therapy with cytotoxic agents or dexamethasone appear promising, although these data need to be confirmed in a larger number of patients. The serendipitous discovery of I-DOX as an agent capable of promoting amyloid resorption provides another novel approach in patients with AL amyloidosis. Continued research on the mechanisms of deposition and resorption of these immunoglobulin deposits should provide important information that can be used to design strategies for more effective therapy and, ultimately, prevention of MIDD.