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

Circulating histamine-releasing factors have been identified in the serum and plasma of chronic-urticaria patients by in vivo skin testing and in vitro histamine release from heterologous mixed leukocytes. Quantitative mast cell studies of serum skin test biopsies and electron microscopy indicate that the serum factors release histamine by mast cell degranulation. Peripheral blood basophils and total cellular blood histamine are reduced in chronic-urticaria patients suggesting that the circulating serum factors cause sustained degranulation. Histamine-releasing activity has been identified by skin testing in ultrafiltered serum fractions less than 30 kDa and greater than 100 kDa. In vitro histamine-releasing activity was confined to ultrafiltered serum fractions greater than 100 kDa and was present in IgG purified from some chronic-urticaria sera by protein G affinity chromatography. The dose-response relationship and kinetics of histamine release in vitro were similar to those of anti-human IgE. 'Desensitisation' of basophils by prior incubation with anti-IgE in the absence of calcium and competitive inhibition studies with myeloma IgE serum indicated that histamine-releasing autoantibodies in chronic-urticaria sera and purified IgG have the properties of anti-IgE. Plasma exchange in 4 patients with active chronic urticaria refractory to antihistamine therapy showing in vivo and in vitro histamine-releasing activity was followed by temporary remission of disease activity in 2 of them. It is possible that chronic urticaria is an autoimmune disease.
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PMID:Histamine-releasing autoantibodies in chronic urticaria. 172 16

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

Hybridoma technology has made the production of antigen-specific monoclonal antibodies feasible and almost routine, but the production of certain biologically desirable antibody isotypes has remained difficult. Three strains of autoimmune mice (MRL/l, NZB, and BXSB) were compared to a normal strain (BALB/c), in fusions with a BALB/c myeloma (NS-1) in order to study the rescue of relevant isotypes with the desired antigenic specificities. Mice from these four strains were immunized with colon carcinoma cells, and the hybridoma supernatants from thirty fusions were analyzed for (1) reactivity with cell surface determinants on the immunizing cell line; and (2) Ig class and subclass isotypes. We found that compared to BALB/c mice, MRL/l mice produced greater numbers, and NZB and BXSB mice comparable numbers, of cell surface-reactive hybridoma clones per fusion. MRL/l mice produced the largest number and highest percentage of cell-surface reactive IgG2a (22.4%) and IgG3 (10.6%) producing clones, followed by NZB mice which produced predominantly IgG2a clones (12.3%). BXSB mice, which have latent autoimmune disease, showed no significant difference from normal BALB/c controls (IgG2a:0.7% and IgG3:1.9% vs. IgG2a:4.8% and IgG3:4.8%). The increase in IgG2a and IgG3 clones derived from MRL/l mice was age-dependent, correlating with the age at which abnormal proliferation of T cell and splenic enlargement occurs (2-4 months). We conclude that MRL/l mice are useful for generating monoclonal antibodies of the IgG2a or IgG3 isotype, provided fusions are performed at the time of maximal lymphoproliferation.
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PMID:Increased yields of IgG2a- and IgG3-secreting hybridomas after fusion of B cells from mice with autoimmune diseases. 196 Apr 13

We have adopted an idiotypic approach to study the double stranded DNA (dsDNA) binding antibodies of systemic lupus erythematosus (SLE). Three anti-idiotypic reagents, 8.12, 3I, and F4, identify cross reactive idiotypes that are each expressed on anti-dsDNA antibodies in the sera of many patients with SLE. These idiotypic antibodies are implicated in the pathogenesis of SLE as they are present in immune complex deposits in the kidneys of patients with SLE glomerulonephritis. The autoantibody associated idiotypes are also expressed on antibodies that do not bind DNA. We are investigating the origin of the pathogenic anti-dsDNA antibodies of SLE by comparing the autoantibodies, the antibodies to foreign antigens, and the myeloma proteins that express each SLE associated idiotype. In conjunction with serological analysis of these idiotypic systems, molecular genetic studies indicate that both the 8.12 and the 3I autoantibody associated idiotypes may be germline encoded, while the F4 idiotype is generated by somatic mutation. The data further suggest that the antigenic specificity of the pathogenic anti-DNA antibodies of SLE is acquired through somatic mutation of germline immunoglobulin genes. By studying the regulation of genes capable of encoding pathogenic autoantibodies, in both SLE patients and non-autoimmune individuals, we may be able to elucidate the pathogenesis of autoimmune disease and begin to design more effective therapeutic interventions.
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PMID:Pathogenic anti-DNA antibodies in SLE: idiotypic families and genetic origins. 215 18

We have recently isolated and characterized a human monoclonal autoantibody, MOR-h1 (multiple organ-reactive human 1), that reacts with antigens in multiple organs and have shown that this antibody binds to human growth hormone and a 35,000-mol wt protein. In the present study we generated three monoclonal anti-idiotypic antibodies (4E6, 3E5, and 3F6) against MOR-h1. These anti-idiotypic antibodies specifically reacted with MOR-h1 and not with 26 other multiple organ-reactive monoclonal IgM autoantibodies nor with pooled human IgM (myeloma proteins). The binding of the anti-idiotypic antibodies to MOR-h1 was inhibited by both human growth hormone and the 35,000-mol wt protein, which strongly suggests that these antibodies react with epitopes at or near the paratope on MOR-h1. The results of competitive binding experiments revealed that the epitope recognized by 4E6 is distinct from that recognized by 3E5 and 3F6. Using these anti-idiotypic antibodies, lymphocytes and sera from normal individuals were tested for the presence of the 4E6 and 3E5/3F6 idiotopes. By indirect immunofluorescence, the 4E6 idiotope was detected on an average of 1.1% of normal circulating B lymphocytes, and by enzyme-linked immunosorbent assays, the 4E6 and to a lesser extent the 3E5/3F6 idiotopes were found on IgG molecules in sera of normal individuals. In spite of the expression of idiotopes known to be present on MOR-h1, no MOR-h1-like antibody activity was detected in normal sera. Examination of sera from patients with several autoimmune diseases failed to show an increased expression of the 4E6 idiotope as compared with normal controls. These data suggest that anti-idiotypic antibody 4E6 recognizes a public idiotope, the expression of which is not restricted to autoimmune disease.
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PMID:Anti-idiotypic antibodies against a human multiple organ-reactive autoantibody. Detection of idiotopes in normal individuals and patients with autoimmune diseases. 241 22

The one-direction radial diffusion method has been used in studies of the blood sera from 75 subjects and the kappa and lambda immunoglobulin types levels have been determined. The kappa:lambda (K:L) index was also calculated. The index values in sera of 20 healthy subjects remained in the range from 1.58:1 to 2.14:1 (mean: 1.86:1). The normal index values have been stated in 5/5 sera of patients with bacterial pneumonia. In 12/12 sera from patients with plasma cell myeloma the significant abnormalities of the index values have been noted. Abnormal index values have also been stated in 9/10 patients with acute leukemia, 4/9 patients with chronic lymphocytic leukemia, 7/8 patients with lupus erythematosus and 4/4 patients with autoimmune hemolytic anemia. The quantitative determination of particular immunoglobulin types may be useful in the diagnostics of the immunoglobulin types may be useful in the diagnostics of the immunoglobulin monoclonal synthesis. The abnormalities of the K:L index observed in patients with leukemias and autoimmune disease suggest that these diseases are frequently characterized by the monoclonal synthesis of immunoglobulins.
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PMID:[Serum immunoglobulin types and their levels in patients with proliferative and autoimmune diseases of the hematopoietic system]. 250 35

Sera from 75 patients with monoclonal gammopathies and with no clinical evidence of autoimmune disease have been screened for a wide range of autoreactivity including binding to DNA, cardiolipin, extractable nuclear antigen (ENA), rheumatoid factor activity and the presence of the common anti-DNA antibody idiotype PR4. The sera of 17/75 (23%) patients possessed autoreactivity: six were positive for anti-DNA activity, two had anticardiolipin activity and the PR4 ID was found in two sera (both of which possessed anti-DNA activity). Antibodies to ENA were found in one serum (anti-Ro) and anti-organ-specific antibodies in five. Using iso-electric focusing and immunoblotting we have shown that the PR4 ID and DNA binding activity are carried on the paraprotein and not on some other serum constituent. The IgG subclass distribution of 55 IgG paraproteins has also been investigated. The majority of IgG paraproteins belong to IgG1 subclass (55%), with the others, being IgG2 (4%), IgG3 (9%) and IgG4 (27%). In this study we have shown that sera from myeloma patients frequently possess autoreactivity, and that in many cases this can be attributed to the paraprotein.
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PMID:Analysis of autoantibody reactivity and common idiotype PR4 expression of myeloma proteins. 250 59

Human monoclonal antibodies produced by Epstein Barr (EB) virus transformation and/or cell fusion are frequently IgM antibodies which tend to cross react with a range of antigens and often bear little relationship to the highly specific IgG antibodies associated with human autoimmune disease. By fusing EB virus transformed B lymphocytes from a Hashimoto patient with a mouse myeloma line and selecting for synthesis of IgG class thyroglobulin (Tg) antibody, we have developed a hybridoma (VB/5) secreting Tg antibody of IgG2 subclass and lambda light chain type which has the characteristics of a monoclonal antibody on isoelectric focussing. The antibody has a high affinity for human Tg and recognises Tg from other primates but not non-primate Tg. However, it does not react with human thyroid peroxidase or a panel of other autoantigens. In terms of affinity constant, functional affinity and affinity heterogeneity, the antibody closely resembles the IgG2 lambda Tg antibody present in the serum of the Hashimoto patient whose B lymphocytes were used to develop the hybridoma. In addition to providing a useful reference standard for Tg antibody IgG subclass assays, VB/5 antibody and the hybridoma line provide a valuable starting point for detailed studies of Tg autoantibodies and the genes coding for the variable regions of their heavy and light chains.
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PMID:A human-mouse hybridoma which secretes monoclonal thyroglobulin autoantibody with properties similar to those of the donor patient's serum autoantibody. 256 81

Sera from patients with adult T-cell leukemia and asymptomatic carriers of human T-cell lymphotropic virus type I (HTLV-I) from widely separated areas of the world reacted strongly in a standardized quantitative enzyme-linked immunosorbent assay procedure with HTLV-I viral antigen prepared from a strain isolated in the United States. There was a sharp differentiation of the values seen in the patients as compared with a normal population. Of the 35 acquired immune deficiency syndrome patients with Kaposi's sarcoma, only 2 were positive for HTLV-I antibodies in this test, and the distribution of the negative assay values in the other acquired immune deficiency syndrome patient sera was similar to that seen in the normal sera. Sera which contained extremely high levels of antibodies to other unrelated viruses (rubella virus, cytomegalovirus, and herpes simplex virus) all showed negative anti-HTLV-I results, in a pattern similar to the normal sera. Sera from patients with several autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, thyroiditis) as well as those with infectious mononucleosis or myeloma all also showed the normal distribution of negative results, in spite of the presence of very high levels of the autoantibodies, etc., associated with their illnesses.
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PMID:Quantitative estimation by a standardized enzyme-linked immunosorbent assay of human T-cell lymphotropic virus type I antibodies in adult T-cell leukemia and acquired immune deficiency syndrome. 300 30

Human monoclonal antibodies are desirable, especially as therapeutic agents, but the best means of producing them is still a matter of investigation. It is clear that human antibodies of predicted specificity from patients with autoimmune disease can be derived, and this may help unlock some of the mysteries of these illnesses. Human monoclonal antibodies against tumor-specific antigens for use in in vivo diagnosis and therapy remain desirable goals. Problems involved in their routine development include the lack of available, adequately immunized, and differentiated lymphocytes and the nature and paucity of the available human "myeloma" cell lines. These lines have been compared now by a number of authors who have reached similar conclusions. Our study directly compared the greatest number of cell lines and found UC729-6 and HF2 to be the best; on the other hand, our success in developing IgG-secreting hybridomas from U-266, using hyperimmunized lymphocytes, suggests that this line may only be capable of secretion with the more differentiated cell, the human equivalent of those hyperimmunized murine spleens. Hence both sides of the fusion equation must be made optimal. Two new approaches to circumvent this problem involve the use of either a human-murine myeloma chimera as the parental myeloma line or, more recently, genetic engineering techniques to substitute human constant regions for the murine while retaining the murine hypervariable region, preserving the binding specificity of the murine antibody.
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PMID:Optimal strategies for developing human-human monoclonal antibodies. 301 63


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