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)

Immunization of BALB/c mice with the mouse anti-CD4 monoclonal antibody (mAb) HP2/6 resulted in the production of anti-idiotypic antibodies. Analysis of the kinetics of the development of anti-idiotypic antibodies showed a homogeneous response among the immunized animals. Cross-blocking assays performed with anti-CD4 mAbs OKT4, OKT4c and OKT4d showed that syngeneic anti-idiotypic antiserum elicited with mAb HP2/6 recognizes idiotope(s) expressed only on the immunizing mAb. The idiotope(s) is (are) located within or closely related to the antigen-combining site of mAb HP2/6. Hybridization with the myeloma cell line NSO of splenocytes from a BALB/c mouse hyperimmunized with mAb HP2/6 generated the anti-idiotypic mAbs F11-2113, F11-2302 and F11-2444 which recognize idiotope(s) outside the antigen-combining site of mAb HP2/6. Although the anti-idiotypic mAbs cross-inhibit each other in their binding to mAb HP2/6, they differ in the ability to elicit anti-anti-idiotypic antisera. Furthermore, mAb F11-2113 enhances CD4 down-regulation in the presence of mAb HP2/6 to a larger extent than mAbs F11-2302 and F11-2444. The latter results suggest an additional mechanism by which anti-idiotypic antibodies may induce functional abnormalities of CD4+ T cells in human immunodeficiency virus-infected T cells.
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PMID:Immunochemical and functional characterization of anti-idiotypic antibodies to a mouse anti-CD4 monoclonal antibody. 181 63

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes. Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B-cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non-Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events.
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PMID:Non-Hodgkin lymphoma in common variable immunodeficiency. 182 73

We have recently demonstrated that the CD24 antigen density of bone marrow (BM) lymphoid cells discriminates between pre-B cells and mature B-cells. Using this new method, we evaluated the B-cell lineage in the BM and peripheral blood (PB) of 18 patients with multiple myeloma (MM). First, the percentage of pre-B cells was significantly reduced by 40% in the BM of patients with MM: 2.3% +/- 2.2% versus 5.7% +/- 2.8% of normal BM lymphoid cells (P less than 0.01). This finding was associated with a significant reduction (50%) of the percentage of mature B-cells in both BM and PB, especially in patients with progressive disease (P less than 0.05). In contrast to what has been reported previously, we have not found any pre-B cells in the PB of these patients with MM. Secondly, BM pre-B and B-cell patients with MM did not express any activation markers (CD23, CD25, or CD71 antigens) and no CD5+ B-cells were found in the BM unlike in PB (8% CD5+ B-cells). Taken together, these data do not support the concept of a direct involvement (i.e, expansion or activation) of pre-B cells in MM without excluding the possibility of an early oncogenic event at the pre-B cell stage. Furthermore, our data emphasize this important reduction of the B-cell compartment (including that of pre-B cell) as a major cause of the humoral immunodeficiency in MM.
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PMID:No expansion of the pre-B and B-cell compartments in the bone marrow of patients with multiple myeloma. 190 6

beta 2-Microglobulin (beta 2M), an interesting and underutilized metabolite, can be used in assessing renal function, particularly in kidney-transplant recipients and in patients suspected of having renal tubulointerstitial disease. It also can serve as a nonspecific but relatively sensitive marker of various neoplastic, inflammatory, and infectious conditions. Early hopes that it would be a useful serum test for malignancy have not been fulfilled, but it does have prognostic value for patients with lymphoproliferative disease, particularly multiple myeloma. More recent reports have suggested a role for beta 2M as a prognostic marker in human immunodeficiency virus (HIV) infection.
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PMID:Beta 2-microglobulin: its significance and clinical usefulness. 218 62

T cell glycoprotein CD4 binds to class II major histocompatibility molecules and to the human immunodeficiency virus (HIV) envelope protein gp120. Recombinant CD4 (rCD4) bound to polyclonal immunoglobulin (Ig) and 39 of 50 (78%) human myeloma proteins. This binding depended on the Fab and not the Fc portion of Ig and was independent of the light chain. Soluble rCD4, HIV gp120, and sulfated dextrans inhibited the CD4-Ig interaction. With the use of a panel of synthetic peptides, the region critical for binding to Ig was localized to amino acids 21 to 38 of the first extracellular domain of CD4. CD4-bound antibody (Ab) complexed with antigen approximately 100 times better than Ab alone. This activity may contribute to the Ab-mediated enhancement of cellular HIV interaction that appears to depend on a trimolecular complex of HIV, antibodies to gp120, and CD4.
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PMID:Human CD4 binds immunoglobulins. 236 51

High grade B-cell lymphoma and leukemia have been well described in patients with the acquired immunodeficiency syndrome (AIDS). Malignant transformation of more differentiated lymphoid cells has not been well described in these patients. We report a 26-year-old man with AIDS-associated multiple myeloma, who had a highly unusual presentation and clinical course. A review of the literature indicates that monoclonal gammopathy in patients seropositive for the human immunodeficiency virus (HIV) is common. Multiple myeloma and extramedullary plasmacytomas, diseases that are extraordinarily rare in young persons, are now being reported in patients with AIDS and should be added to the list of neoplastic diseases now associated with HIV infection.
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PMID:Nonsecretory multiple myeloma in a 26-year-old man with acquired immunodeficiency syndrome, presenting with multiple extramedullary plasmacytomas and osteolytic bone disease. 236 18

The characteristics of T and B lymphocyte profile and B lymphocyte specificity repertoire were compared in patients with Waldenstrom's macroglobulinemia (WM), IgM monoclonal gammopathy of undetermined significance (IgM MGUS), multiple myeloma (MM), and age-matched normal subjects. Patients with MM had both significantly reduced frequency and number of sIg+ (surface Ig) B cells, whereas patients with WM and IgM MGUS had a reduced frequency but normal numbers of sIg+ B cells in circulation as detected in a capping assay. WM was distinguished by the large numbers of cells in the peripheral blood lymphocyte (PBL) pool that expressed CD9 (BA-2) and CD24 (BA-1) and were monoclonal, based on light chain analysis using flow cytometry. The profile of T lineage cells showed that the ratio of CD4:CD8 was significantly reduced in both MM and WM due to a reduction in the CD4 set. The CD4+ cells were qualitatively abnormal as well, with an enriched proportion of the 4B4+ (CDw29) subset and decreased proportion of the Lp220+ (CD45R) subset. This appeared to be an effect of the disease process on the relatively immature Lp220+ set. From clonal analysis, those patients with WM or IgM MGUS (unlike MM patients) did not exhibit enhanced reactivity with auto-Ig determinants, and most WM patients (7/8) and half of the IgM MGUS patients (3/6) did not have enriched proportions of B cells reactive to tetanus toxoid (TT). The TT-specific B cells in both WM and IgM MGUS, in contrast to MM, appeared fully functional in secretion of anti-TT IgM in vivo. We speculate that the more severe immunodeficiency in MM may be controlled or exacerbated by the presence of an anti-Ig network. The absence of this network in WM allows a relatively more effective immune response, but the immunodeficiency that is observed in these patients involves some abnormality in normal lymphocyte differentiation (is also present in MM).
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PMID:Abnormalities in lymphocyte profile and specificity repertoire of patients with Waldenstrom's macroglobulinemia, multiple myeloma, and IgM monoclonal gammopathy of undetermined significance. 253 15

For functional characterization and semi-quantitative estimation of soluble regulator factors influencing polyclonal B cell proliferation and differentiation, we established two assays. One of the assays measures enhancement or inhibition of proliferation from purified human spleen B lymphocytes, and the other one the effect of soluble factors on CESS-cell differentiation. We found no difference concerning regulator factors for B cell differentiation between bone marrow cell culture supernatants from multiple myeloma (MM) patients and from controls, whereas significantly higher suppressor activity on polyclonal B cell proliferation could be detected in the former group of supernatants. The extent of such determined suppressor activity in vitro correlated with the amount of polyclonal serum IgM of the corresponding patients. These results indicate that one or several soluble suppressor factors may be involved in immunoregulatory mechanisms responsible for the humoral immunodeficiency observed in MM patients.
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PMID:Suppression of polyclonal B cell proliferation mediated by supernatants from human myeloma bone marrow cell cultures. 278 37

We have established a program to make human monoclonal antibodies to the human immunodeficiency virus (HIV). Lymphocytes of lymph nodes from patients with the acquired immunodeficiency syndrome (AIDS) related complex (ARC) spontaneously produced antibodies to HIV in vitro and their antibody production was suppressed by culturing them in the presence of HIV antigens. Therefore, in vitro stimulation with HIV antigens was not done but rather, donor lymph node or spleen lymphocytes were directly fused with mouse myeloma cells. One of the hybridomas thus generated has been stably producing human monoclonal antibody (MAb) of the IgG1 isotype with a kappa chain. This antibody, MAb86, bound to the surface membrane of HIV-infected cells but not to that of uninfected cells at all. MAb86 reacted in Western blot with both viral glycoproteins of 120,000 daltons (gp120) and 41,000 daltons (gp41). While not neutralizing alone, a combination of MAb86 with another human IgG1 MAb against gp120 showed viral neutralization. Based on these data it seems likely that this approach will result in human MAbs capable of viral neutralization and antibody-dependent cytotoxicity. These may have value for the prevention and/or treatment of AIDS.
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PMID:Human monoclonal antibody against glycoproteins of human immunodeficiency virus. 284 63

Autologous mixed lymphocyte reaction (AMLR) was measured in 12 patients with multiple myeloma. In ten patients depressed AMLR was found. Depletion of adherent monocytes caused enhancement of AMLR in those with a normal OKT4/OKT8 ratio. Only after monocyte depletion was a high correlation found between the AMLR values and the absolute number of OKT+4-T lymphocytes in the patients' peripheral blood. There was an inverse correlation between the suppressive effect of adherent monocytes on AMLR and the patients' serum levels of polyclonal IgG and IgM. Defects in both monocytes and OKT+4-T cells might have caused the low AMLR values and perhaps played a role in multiple myeloma immunodeficiency.
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PMID:Autologous mixed lymphocyte reaction in multiple myeloma patients: effect of adherent mononuclear cells and T lymphocytes. 294 46


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