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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with myeloma have a depressed capacity to respond to antigenic challenge. Studies in this laboratory have previously described an unclassified lymphoid cell which binds human erythrocytes coated with human immunoglobulin G (IgG) anti-D antibody (EA) as important in the inhibition of Ig synthesis in myeloma patients. Using monoclonal antibodies, two-color fluorescence studies, and flow cytometry, we characterized this EA cell as a Leu-1+ (cluster designation (CD) 5), Leu-12+ (CD 19), Leu-16+ (CD 20), B2+ (CD 21), Leu-14+ (CD 22), and HLA-DR+ B cell. The cell was negative for antibodies to Leu-2 (CD 8), Leu-3 (CD 4), Leu-4 (CD 3), Leu-5 (CD 2), Leu-7, Leu-8, Leu-11 (CD 16), Leu-M1 (CD 15), Leu-M3, and CALLA (CD 10). This profile is consistent with a Leu-1+ B cell and excludes a T cell, natural killer cell, and monocyte. Comparison of the relative role of these cells to the role of monocytes in the suppression of pokeweed mitogen-stimulated Ig synthesis was determined in serial studies on 19 myeloma patients. The mean (+/- SEM) percentage of inhibition of Ig synthesis by monocytes from stage I myeloma patients was 14 +/- 2.2%, from stage II patients was 37 +/- 3.5%, and from stage III patients was 51 +/- 4.7%. Inhibition of Ig synthesis by Leu-1+ EA cells was 46 +/- 1.5%, 48 +/- 1.6%, and 43 +/- 3.7% in stage I, II, and III patients, respectively. Immunosuppressive B cells are an important component of inhibition of Ig synthesis in the immunodeficiency of myeloma.
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PMID:Multiple myeloma: an immunologic profile. IV. The EA rosette-forming cell is a Leu-1 positive immunoregulatory B cell. 295 12

The specificity repertoire of B lymphocytes from 14 multiple myeloma patients has been studied using the technique of Epstein-Barr virus (EBV) transformation of peripheral blood lymphocytes (PBL) coupled with clonal analysis by limiting dilution. We find that up to 100% of the B cells from myeloma patients undergoing EBV transformation secrete IgM specific for determinants on the F(ab')2 region of autologous and/or heterologous monoclonal immunoglobulin. In normal individuals 0.02-0.73% of the transformed B cells secrete IgM specific for F(ab')2 determinants. Two patients with monoclonal gammopathy of undetermined significance had only a weak reactivity to F(ab')2 fragments. The number of anti-F(ab')2 B cells was up to 145-fold greater in patients than in normal donors. The majority of antibodies from patient clones recognized determinants shared among 3-12 different F(ab')2 fragments, whereas those originating from normal donor B cells saw determinants expressed on only one or two of the panel of test F(ab')2 fragments. There was a preference for autologous M components and a high proportion of antiidiotypic reactivity in five of eight patients so analyzed. We speculate that these findings indicate the existence of an anti-F(ab')2 immunoregulatory network mediating patient immunodeficiency network mediating patient immunodeficiency, thereby creating an abnormality that may enable the progression of multiple myeloma.
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PMID:Specificity repertoire of lymphocytes from multiple myeloma patients. I. High frequency of B cells specific for idiotypic and F(ab')2-region determinants on immunoglobulin. 299 34

Patients with multiple myeloma are generally immunodeficient, with pronounced depression in primary antibody responses. We have attempted to delineate the reasons for the humoral immunodeficiency by analyzing the specificity repertoire of the surface immunoglobulin (Ig)-positive B cells in patients with multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS), in comparison with normal donors. B lymphocytes from 26 patients with multiple myeloma, 12 patients with MGUS, and 8 normal donors were transformed with Epstein-Barr virus (EBV) and cultured at limiting dilution for clonal analysis. The Ig secreted by each clone was analyzed for class and anti-tetanus toxoid (TT) specificity to determine the frequencies of IgM, IgG, anti-TT IgM, and anti-TT IgG antibody-secreting clones. Our objective was to establish whether the inability to mount humoral responses to common environmental pathogens was due to a lack of specific B cells or to inhibition of B-cell function. Our results indicate that the quantitative B-cell deficiency in patients was due to a nonrandom loss of selected sets of B cells. Although most patients had a reduced aggregate number of B cells, the number of TT-specific B cells was normal. There was, on average, a threefold increase in the proportion of the B-cell specificity repertoire devoted to recognition of TT. Forty-four percent of the patients with MGUS were also affected. In addition, the TT-specific B cells in multiple myeloma patients were severely compromised in their ability to secrete antibody or to differentiate to antibody-secreting cells in vivo. This arrest in differentiation appears to be extrinsic to the B cells, as they were fully able to secrete anti-TT antibody after transformation and culture in vitro. We postulate the existence of an autoimmune inhibitory network mediating the arrest in B-cell differentiation and the humoral immune deficiency.
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PMID:Humoral immune deficiency in multiple myeloma patients due to compromised B-cell function. 302 34

The protective effect of passively administered immunoglobulin has been known for many years. Although its accepted use over the last 40 years has been in the prevention and treatment of infection its widest and, arguably, most important application has been in the prevention of Rhesus haemolytic disease of the newborn. However, the development over the last decade of a number of safe and effective immunoglobulin preparations for intravenous use has allowed its more widespread utilisation in clinically appropriate settings. It is now widely accepted that intravenous immunoglobulin (IVIgG) is indicated, on a repeat basis, as treatment of choice as replacement therapy for patients with primary antibody deficiency. It may also be effective, in the non-immune deficient patient, in the management of certain bacterial as well as viral infections. This is particularly the case in the pre-term neonate but may have an application in the infected intensive care patient. The benefit in these patient groups has led to a re-evaluation of the use of immunoglobulin replacement therapy in the severe secondary antibody deficiency states associated with such haematological conditions as multiple myeloma and chronic lymphocytic leukaemia. These are currently the subject of randomised, controlled studies. The observation that the use of IV IgG may be associated with effects other than passive transfer of antibody were first made by Imbach in Switzerland. While treating children with immunodeficiency he noticed that two with a coincident immune thrombocytopenia had a rapid platelet increment in close association with the immunoglobulin infusion. He subsequently confirmed that this was a rapid and predictable form of therapy in childhood idiopathic thrombocytopenic purpura (ITP) and that in some children it appeared to affect the natural history of the disease. Since these initial observations the response has been confirmed in both children and adults and extended to other immune-based haematological disorders.
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PMID:Clinical use of intravenous immunoglobulin in blood disorders. 305 61

The classes, subclasses and light chain types of 78 serum monoclonal immunoglobulins (MoIg) from adult patients affected with various clinical forms of human immunodeficiency virus (HIV) infection were studied by a sensitive Western blot technique. The incidence of MoIg-containing sera was 26% in a systematic study. Most of these sera contained several (up to eight) detectable MoIg. These MoIg were IgG (91%) and IgM (9%) with a predominance of light chains of the lambda type (kappa:lambda ratio 0.6). The subclass distribution of monoclonal IgG was strikingly different from that observed in myeloma; much less IgG1 and much more IgG3 and IgG4.
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PMID:Isotypy of serum monoclonal immunoglobulins in human immunodeficiency virus-infected adults. 314 51

The incidence of infections caused by gram-negative bacteria is increased in patients with multiple myeloma due to secondary humoral immunodeficiency. In order to diagnose patients with increased susceptibility to gram-negative infections, serum antibodies against common determinants of lipopolysaccharides (lipid A and core-polysaccharide) were determined by a rapid enzyme-linked immunosorbent assay (ELISA). It was possible to define a group of patients at high risk of contracting gram-negative infections using this test. Intravenous IgG preparations used as a substitute were shown to contain antibodies against these common antigens. However, it is suggested that the clinically recognized efficacy of these preparations could be due to their containing anti-LPS antibodies.
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PMID:Serum antibodies against common antigens of bacterial lipopolysaccharides in healthy adults and in patients with multiple myeloma. 403 Jan 7

The risk of developing a second primary cancer was evaluated in approximately 19,000 persons with initial cancers of the lymphatic and hematopoietic system in Connecticut between 1935 and 1982. Significant excesses for all second cancers were observed among patients with leukemia (34%), Hodgkin's disease (70%), non-Hodgkin's lymphoma (25%), and multiple myeloma (24%). In general, the risk of second cancers was greater in males than in females, even for cohorts not showing an excess of surveillance-related prostate cancer. Among patients with leukemia, significant excesses of cancers of the lung, kidney/ureter, and prostate were noted; cutaneous melanoma was elevated only in males. These excesses did not persist in the small number of long-term survivors. Possible etiologic factors included tobacco smoking for lung and kidney cancers, medical surveillance artifact for prostate cancer, and immunosuppression for malignant melanoma and lung cancer. The large number and good prognoses of patients with chronic lymphocytic leukemia strongly influenced the pattern of second cancers when all leukemias were analyzed together; no evidence was found for an increased risk of second cancer in patients with acute lymphocytic leukemia. A disproportionate number of subsequent cancers, particularly those of the kidney and ureter, were diagnosed incidentally at autopsy. Patients with Hodgkin's disease displayed significant excesses of cancers of the buccal cavity and pharynx, lung, female breast, and thyroid. The latter 3 sites remained significantly elevated in long-term survivors (10 yr or more postdiagnosis), so that radiation therapy may have contributed to their development. Among persons with non-Hodgkin's lymphoma, cancers of the stomach, lung, brain, and connective tissue occurred excessively. The first 3 sites, plus cancers of the urinary bladder, remained elevated among long-term survivors. The brain cancer excess, not previously reported, may represent misclassification of central nervous system lymphoma. The risk of gastric cancer is reminiscent of similar findings in patients with both acquired and genetically determined immunodeficiency disorders. The alkylating agent, cyclophosphamide, used extensively in the treatment of non-Hodgkin's lymphoma, is known to cause bladder cancer in man.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Second cancer following lymphatic and hematopoietic cancers in Connecticut, 1935-82. 408 98

The distribution of B lymphocytes expressing surface IgG subclasses has been defined by using immunochemically purified, subclass-specific, F(ab')2 fragments. Studies in normal adults showed 1.16% of peripheral lymphocytes to be positive for IgG. Percentages of IgG subclasses were IgG2, 0.50%; IgG4, 0.40%; IgG1, 0.33%; and IgG3, 0.14%. Dual label experiments indicated that minor subpopulations of normal lymphocytes may express more than one IgG subclass, both on surface IgG as well as in the cytoplasm. Cord blood showed significantly less IgG4-positive cells than were present in adults. Preliminary studies of patients with common variable immunodeficiency showed shifts in cell populations paralleling those previously noted in serum. Some patients with multiple myeloma were noted to exhibit striking shifts in the distribution of B lymphocytes toward a population of cells showing a similar IgG subclass to that of the M-component.
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PMID:Distribution of IgG subclasses in human B lymphocytes: evidence for dual expression of subclasses in surface and cytoplasmic IgG in minor B lymphocyte subpopulations. 696 97

Genetic factors suspected in the etiology of human hemopoietic neoplasia, such as leukemia, lymphoma and multiple myeloma, are reviewed. High incidence of consanguineous marriage was found in parents of familial leukemia in siblings. It was also noted that the age of patients with familial leukemia in children of consanguineous parents was younger than that of cases whose parents were not related. These findings suggest that genetic factors may play an important role in the etiology of familial leukemia in siblings. According to the frequencies of familial aggregations in close relatives, the genetic relationships were supposed to be important in chronic lymphocytic leukemia and acute leukemia, but not in chronic granulocytic leukemia. Increased prevalence of autoimmune diseases in relatives of leukemic patients suggests a possibility of genetic immunodeficiency as a common etiologic factor in both diseases. Immunodeficiency was found in unaffected relatives of patients with familial leukemia and lymphoma. Genetic factors were also suggested by the familial occurrences of multiple myeloma and primary macroglobulinemia, and the incidence of benign monoclonal gammopathy in relatives of patients with these diseases. HLA studies revealed the increased frequencies of A2 in acute lymphocytic leukemia, of B5 and B18 in Hodgkin's disease, and of A5 and B18 in multiple myeloma. From such relationships existing between familial immunodeficiencies and hemopoietic neoplasia, genes regulating the immune responsiveness might be involved in susceptibility to these diseases.
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PMID:[Genetics and hemopoietic neoplasia]. 718 26

In 1974 and 1975 7000 patients' sera were tested for levels of IgG, IgA and IgM. In 330 patients at least one of the three Ig classes was low. In most instances secondary immunodeficiency was present in association with myeloma, etc. However, 81 patients above 8 years of age fulfilled the criteria of idiopathic late onset Ig deficiency. In 44 of these patients clinical follow-up and repeated measurements of Ig levels were possible 1--8 years after the initial diagnosis. Selective IgA deficiency was present initially (15 patients) most frequently and persisted most often (14 patients). 4 patients had initially low IgG and 6 patients low IgM, findings which were only rarely confirmed later on. In 19 patients 2 or 3 Ig classes were initially low, with persistence of Ig deficiency in 12 individuals. In no instance had clinical symptoms appeared in the first two years of life. The following diseases were documented in the 44 patients studied (28 individuals with persistent and 16 with transitory Ig deficiency): recurrent infections (16 patients), atopic disease (8 times), rheumatoid arthritis (6 times), epilepsy (4 times), SLE (3 times) and enteropathies (twice). Seven patients also had a malignancy, 4 diabetes, and 2 hyperthyroidism.
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PMID:[Idiopathic immunoglobulin deficiency in juveniles and adults. Catamnestic studies]. 739 75


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