Abnormal immunoglobulin synthesis in monoclonal immunoglobulin light chain and light and heavy chain deposition disease.
The Congo red-binding fibrils of AL amyloidosis are the most common form of monoclonal immunoglobulin tissue deposition (MIDD). Nonetheless, the less structured deposits found in light chain deposition disease (LCDD) and the similar, but distinct, deposits of light and heavy chain deposition disease (LHCDD) and heavy chain deposition disease (HCDD) can produce significant clinical pathology. Analyses of immunoglobulin synthesis by bone marrow cells obtained from 7 patients with LCDD and LHCDD demonstrated the production of excess light chains in all and the presence of incomplete light chains or heavy chain fragments in 5, regardless of the presence of an intact monoclonal protein or related subunit in the serum or urine. Our data indicate that, as is the case with the fibrillar deposits of AL amyloid, the non-fibrillar forms of monoclonal Ig deposition (LCDD and LHCDD) can be associated with the presence of immunoglobulin fragments in bone marrow cells. In some instances these appeared to be synthetic in origin, although rapid intracellular proteolysis or a combination of both could not be excluded. In either case the fragments may be more susceptible to tissue deposition, with subsequent organ compromise, than intact Ig chains.
Buxbaum
J N
JN
Research Service New York V.A. Medical Center, Departments of Medicine and Pathology and Kaplan Cancer Center, New York University School of Medicine, New York City, NY, USA. jbux@scripps.edu
D000686:Amyloidosis / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D012634:Bodily Secretions / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism*; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D006362:Heavy Chain Disease / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000276:immunology / Q000378:metabolism*; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000097:blood / Q000652:urine
D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins