pH-dependent fibrillogenesis of a VkappaIII Bence Jones protein.

Disorders of immunoglobulin (Ig) synthesis that occur in malignant plasma-cell proliferation may result in either granular (LCDD) or fibrillar (AL) tissue deposition of light-chain monoclonal components. The structural features that govern the transition from soluble polypeptides to either fibrillar or granular conformational states remain undefined. Among the many factors presumed to play a role in these transitions the net charge of the molecule has been associated with folding conformation changes.

IgG1-kappa biclonal gammopathy associated with multiple myeloma suggests a regulatory mechanism.

Multiclonal gammopathies associated with multiple myeloma may result either from a neoplastic transformation of a cell clone undergoing immunoglobulin class switching or from independent transforming events yielding proliferation of unrelated plasma cell clones. The simultaneous presence of more than one neoplastic clone may possess regulatory implications in terms of cell proliferation, clonal expansion, secretion of M-components or response to chemotherapy. We report a patient, diagnosed with multiple myeloma stage IIIa, who presented with two well-defined homogeneous IgG1-kappa components in the serum (designated WER-1 and WER-2) with striking differences in their plasma concentration and response to the classic melphalan/prednisone treatment.

Alzheimer's soluble amyloid beta is a normal component of human urine.

Soluble A beta (Sa beta) is normally present at a low concentration in human plasma and cerebrospinal fluid. Although the factors involved in the regulation of Sa beta plasma levels are still unknown, we have explored its excretion in the urine as one of the possible homeostatic mechanisms. The presence of Sa beta in the urine was investigated via immunoprecipitation experiments with anti-A beta antibodies followed by detection and identification by immunoblot, MALDI mass spectrometry and sequence analysis.

Fibrillary glomerulonephritis related to serum fibrillar immunoglobulin-fibronectin complexes.

Fibrillary glomerulonephritis is a disease of uncertain origin and pathogenesis characterized by nonamyloidotic fibrils in glomeruli. We report immunohistological, immunochemical, and biochemical studies of a serum fibrillar cryoprecipitate obtained from a patient with fibrillary glomerulonephritis, that formed on prolonged storage at 4 degrees C. By Western blot and amino acid sequence analysis, the cryoprecipitated fibril components consisted of immunoglobulins, heavy chains gamma and mu, light chains kappa and lambda, and fibronectin, similar to the proteins identified by immunofluorescence and immunoelectron microscopy in the glomerular fibrils.

Susceptibility of monoclonal IgG paraproteins to plasmic cleavage using glycerin-stabilized human plasmin.

To shed further light on plasmin-IgG interactions a simple procedure is described that permitted 48 monoclonal IgG isolates from human serum to be profiled for their susceptibility to plasmic cleavage. In addition to anodal Fc and cathodal Fab fragments, combined immunoelectrophoresis-electrophoresis revealed transient anodal banding, as well as Fab-fragment subcleavage in many of the IgG subclass-1 isolates. The subcleavage of released Fab fragments, which bear the idiotype determinants, points to a possible ancillary role of plasmin in "idiotype processing" leading to immunoregulatory anti-idiotype networks.