Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mAb of the IgG1/kappa isotype was raised against human myelin basic protein (MBP) peptide acetyl 1-9. This mAb, termed F23, reacted with human MBP and human MBP peptides acetyl 1-9, 1-14, and 1-44, but not with MBP peptides 10-19, 80-89, or 45-89. According to the guidelines of the molecular recognition theory, a complementary peptide to human MBP peptide 1-9 was synthesized and used to raise murine mAb with anti-Id activity. Two mAb anti-Id, F25F7 and F25C8, both of the IgM/kappa isotype, were selected for further study. These anti-Id reacted with F23, the mAb for which they were selected, and also reacted with another mAb, which was of the IgG1/kappa isotype and was raised to human MBP peptide 80-89. There was no reaction with another control mAb of the IgG1/kappa isotype or murine myeloma IgG1. By immunoblotting techniques, it was demonstrated that the Id on each of the mAbs to MBP peptides was located on the kappa L chain but also could be recognized in nonreduced IgG. The cross-reactive anti-Id suppressed antibody secretion of Id-producing hybridoma cells in an Id-specific manner, and kinetic studies suggest an intracellular mechanism for the suppression. These cross-reactive Id among antibodies to different MBP peptides imply that the same V region genes of kappa L chains are involved in the selection of antibodies to an autoantigen, like MBP, and may play a role in the modulation of immune responses against MBP in certain inflammatory demyelinating diseases.
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PMID:An idiotype shared by monoclonal antibodies to different peptides of human myelin basic protein. 169 57

Great numbers of CD5+ B lymphocytes were detected in the peripheral blood of patients with B-CLL. To study the antibody repertoire of this immune cell subpopulation on a monoclonal level, we fused the lymphocytes derived from five different donors to a highly efficient HAT-sensitive heteromyeloma line (CB-F7). A fusion frequency of up to 10(-5) allowed us to analyse hundreds of initial hybridoma lines per fusion. In all culture supernatants in three out of five fusions IgM lambda antibodies were detected, in two experiments only IgM kappa was measured, suggesting monoclonality of the primary hybridoma cell lines. The later fusions resulted in hybridomas producing multi-specific antibodies against both an autoantigen and an infectious agent: (i) dsDNA/influenza virus haemagglutinin; (ii) dsDNA/class V outer membrane protein type C from Neisseria meningitidis. However, no antibodies of the described specificity were detected in blood sera of patients, indicating a 'switch-on' of the immunoglobulin secretion capacity of malignant B cells during fusion to a myeloma partner. We discuss the results as further evidence for the natural multi-reactive antibody repertoire of CD5+ B cells.
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PMID:Human hybridomas derived from CD5+ B lymphocytes of patients with chronic lymphocytic leukemia (B-CLL) produce multi-specific natural IgM (kappa) antibodies. 170 36

A 64-year-old lady with a personal and family history of autoimmune disease developed chronic myelomonocytic leukaemia and multiple myeloma simultaneously. Her sister died of acute myelomonocytic leukaemia, but showed no evidence of autoimmune disease. It is possible that chronic immunological stimulation, perhaps by an autoantigen, may predispose toward malignant transformation in both plasma cell and monocyte series. However, the present observations raise the alternative possibility of a primary disorder of monocytes that predisposes toward both autoimmune disease and a clonal disorder of plasma cells.
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PMID:Multiple myeloma and chronic myelomonocytic leukaemia developing in a patient with autoimmune disease. 191 30

MRL-lpr/lpr mice spontaneously develop a lupus-like syndrome characterized by immunopathological manifestations such as necrotizing vascular lesions of ear tips and severe glomerulonephritis. Similar skin vascular and glomerular lesions associated with cryoglobulinemia can be induced in normal mice by injection of a monoclonal antibody (mAb)--6-19 (gamma 3 heavy chain and kappa light chain), exhibiting both cryoglobulin and anti-IgG2a rheumatoid factor (RF) activities--derived from the MRL-lpr/lpr autoimmune mouse. To determine the role of RF and/or IgG3 Fc fragment-associated cryoglobulin activities in 6-19 mAb-induced tissue lesions, a 6-19-J558L hybrid mAb (gamma 3 heavy chain and lambda 1 light chain) was produced by fusion between the 6-19 hybridoma and the J558L myeloma. Here we report that the 6-19-J558L hybrid mAb, which loses the RF activity but retains the cryoglobulin activity, fails to induce skin vascular lesions. However, it is still able to provoke glomerular lesions identical to those caused by the 6-19 mAb. Further, we have observed that the depletion of the corresponding autoantigen, IgG2a, in mice by treatment with anti-IgM antisera from birth also prevents the development of skin but not glomerular lesions. Our results indicate that both RF and cryoglobulin activities of the 6-19 mAb are required for the development of skin vasculitis, but its cryoglobulin activity alone is sufficient to cause glomerular lesions. In addition, cDNA cloning and sequencing of the 6-19 mAb has revealed that the 6-19 kappa light chain variable region amino acid sequence is encoded in a germ-line configuration, suggesting that immunoglobulin variable region germ-line genes could contribute to the generation of pathogenic autoantibodies.
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PMID:Cryoglobulinemia induced by a murine IgG3 rheumatoid factor: skin vasculitis and glomerulonephritis arise from distinct pathogenic mechanisms. 226 5

Antigen expression is studied corresponding to a monoclonal autoantibody (IC2) derived from a hybridoma of rat myeloma Y3 cells and splenocytes of the diabetic BB rat. The selective reactivity of IC2 with islet cells has earlier been proven. We studied the possible specificity for beta islet cells, and the possible variation in autoantigen expression. Islet cells were isolated by cautious collagenase and dispase treatment. The cells were labelled with IC2 alone or together with anti-insulin immunoglobulin in double-labelling experiments. Extensive series of cells were examined by immunofluorescence microscopy, and some samples also by flow cytometry. In double-labelling examinations we found that only anti-insulin positive cells could bind the IC2 antibody, thus showing beta-cell selectivity. On the other hand, not all anti-insulin positive cells were IC2-positive. Since insulin treatment has been shown to decrease the incidence of diabetes in the BB rat, islet cells were examined after reduced beta-cell strain. Islet cells from Lewis and Wistar Furth rats display 21.4 +/- 1.4% IC2-positive cells, while islet cells from 24-hour fasting animals showed 7.0 +/- 1.4% (p less than 0.0001). Similar results were seen for BALB/c mice (25.0 +/- 1.8% vs. 13.7 +/- 2.3%, p less than 0.002). Also, after a week of insulin treatment, autoantigen expression was significantly decreased. Thus, the IC2 antibody is beta-cell-specific, and expression of the corresponding cell surface antigen depends on the functional state of the beta-cells.
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PMID:Antigen expression of the pancreatic beta-cells is dependent on their functional state, as shown by a specific, BB rat monoclonal autoantibody IC2. 328 66

Somatic cell hybridization of NS.1 nonsecretor myeloma cells with spleen cells of (DBA/2 X C57BL/6)F1 mice immunized against the myeloma MOPC 70A of BALB/c mice led to the establishment of five hybridoma clones which continuously secrete anti-MOPC 70A cytotoxic antibodies. The respective antigen detected by each of the five monoclonal antibodies is expressed both on plasmacytomas and on antibody-secreting cells as the only normal cell type. The tissue distribution of this new antigen is different from that reported for the alloantigen PC.1, and we have therefore designated it as PC.2. On the basis of immune elimination of direct and indirect plaque-forming cells, all mouse strains tested express PC.2 determinants, identifying PC.2 essentially as an autoantigen. Conventional anti-PC.1 alloantiserum contains antibodies to the PC.2 determinant, and these antibodies are distinguishable from the anti-PC.1 antibodies proper by the fact that only the latter are absorbed by liver cells. Monoclonal anti-PC.2 antibodies are not directed against MuLV-(murine leukemia virus)--associated antigens as over 20 ecotropic, several MCF (mink colony forming recombinant, and xenotropic viruses failed to react in immunofluorescence assays.
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PMID:A new surface antigen (PC.2) expressed exclusively on plasma cells. 615 21

During the course of immunizing balb/c mice with eye muscle (EM) or thyroid (THY) membranes for monoclonal antibody (MCAB) production their sera frequently contain antibodies which react against both EM and THY membranes in enzyme-linked immunosorbent assay (ELISA) and SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. In order to further study this phenomenon we have analyzed sera from 27 balb/c mice, including 10 that were studied serially, and their tissues examined histologically at sacrifice. Following immunization serum and, in some cases, the corresponding MCAB produced by fusion of the mouse spleen cells with a mouse myeloma cell line, were tested for EM and THY cross-reactivity in an ELISA and by immunoblotting. The number of antibodies demonstrated in Western blotting identified as bands of reactivity, and ELISA levels, expressed as optical density--increased with time, each peaking at around 10-12 weeks. THY and EM antibody cross-reactivity was demonstrated in the majority of mice, serum from mice immunized with THY membranes reacting with these membranes as well as with pig EM membranes in both ELISA and immunoblotting and, conversely, sera from mice immunized with pig EM membranes also reacting with THY membranes in the two tests. In Western blotting a variety of THY and EM-reactive antibodies were demonstrated including those directed against a 64 kDa protein, shown to be an important autoantigen in thyroid-associated ophthalmopathy. There was also some cross-reactivity with brain membranes, used as control antigen in both tests and in immunization, although to a lesser degree, but very little to liver and orbital connective tissue membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cross-reactive antibodies in the serum of balb/c mice immunized with thyroid or eye muscle membranes. 751 57

Ag activation of the BCR may play a role in the pathogenesis of human follicular lymphoma (FL) and other B cell malignancies. However, the nature of the Ag(s) recognized by tumor BCRs has not been well studied. In this study, we used unbiased approaches to demonstrate that 42 (19.35%) of 217 tested FL Igs recognized vimentin as a shared autoantigen. The epitope was localized to the N-terminal region of vimentin for all vimentin-reactive tumor Igs. We confirmed specific binding to vimentin by using recombinant vimentin and by performing competitive inhibition studies. Furthermore, using indirect immunofluorescence staining, we showed that the vimentin-reactive tumor Igs colocalized with an anti-vimentin mAb in HEp-2 cells. The reactivity to N-terminal vimentin of IgG FL Igs was significantly higher than that of IgM FL Igs (30.4 versus 10%; p = 0.0022). However, vimentin-reactive FL Igs did not share CDR3 motifs and were not homologous. Vimentin was expressed in the T cell-rich regions of FL, suggesting that vimentin is available for binding with tumor BCRs within the tumor microenvironment. Vimentin was also frequently recognized by mantle cell lymphoma and multiple myeloma Igs. Our results demonstrate that vimentin is a shared autoantigen recognized by nonstereotyped FL BCRs and by the Igs of mantle cell lymphoma and multiple myeloma and suggest that vimentin may play a role in the pathogenesis of multiple B cell malignancies. These findings may lead to a better understanding of the biology and natural history of FL and other B cell malignancies.
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PMID:Nonstereotyped lymphoma B cell receptors recognize vimentin as a shared autoantigen. 2353 34

B-cell depleting therapy (BCDT) is effective in suppressing synovitis and erosions in rheumatoid arthritis suggesting that a cell of the B-lymphocyte lineage is critical in the pathogenesis of this disease. Non-Hodgkins lymphoma (NHL) also responds to BCDT but multiple myeloma (MM), does not as cells have differentiated beyond the CD20-bearing stage. However, there are similarities between B-NHL, MM and RA that suggest all 3 conditions could be initiated and perpetuated by the same cellular players. Numerous plasma cells and B cells are present within rheumatoid synovial membrane, and subarticular bone where they contribute to osteitis. On MRI scans this appears as bone oedema, which has been demonstrated to precede the development of bone erosions. Plasma cell clonality has been detected within RA synovial membrane and bone marrow. It is proposed that RA could represent a "forme fruste" of a B cell neoplastic condition, with production of autoantibodies that target a self-antigen within the joint. The activation of rheumatoid bone osteoclasts by anticitrullinated protein antibodies supports this theory. The erosions of RA would have parallels with the lytic lesions of MM but autoantigen targeting dictates that erosions occur at joint margins. This theory is discussed from rheumatologic and haematologic perspectives.
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PMID:Is rheumatoid arthritis a B-cell haematological disease with a predilection for the joints? Following the B cell thread to its logical conclusion. 2444 77