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

A 50-year-old black man had the signs and symptoms of severe anemia. His bone marrow contained sheets of primitive cells that could only be conclusively identified as being of plasmacytic origin by electron microscopy. These cells produced only a small quantity of kappa light chain but did fluoresce when stained with immunofluorescent antikappa stain. His initial response to chemotherapy was dramatic, but after eight months his condition was refractory to all further attempts at treatment. This case supports the observation of Hobbs that patients with Bence-Jones myeloma may have a poorer prognosis than those with otherwise typical IgG or IgA myeloma.
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PMID:Light chain disease: report of an atypical case. 82 46

The complement (C) system can solubilize immune precipitates prepared with antibodies of the IgG class, and apparently also of the IgM class. This paper shows that C can also solubilize immune precipitates prepared with two different antigen-binding IgA myeloma proteins. Immune precipitates were prepared with a) mouse myeloma protein TEPC 15 and PC-KLH, and b) mouse myeloma protein MOPC 315 and DNP-BSA. The precipitates could be solubilized by fresh mouse serum, but not by zymosan- or heat-inactivated serum. The rate of solubilization was not affected by the removal of of Ca++ ions. These results verify that the C-mediated solubilization effect can proceed entirely via the alternative C pathway, and lend increased support to the view that the effect is a general phenomenon, not restricted to a particular antibody class or type of antigen.
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PMID:Solubilization of IgA immune precipitates by complement. 97 53

A lambda, IgAl myeloma protein that formed two chain half-molecules was obtained from a patient who had typical multiple myeloma. His serum contained 1.3 g/100 ml of an IgA paraprotein of gamma-1 electrophoretic mobility, his urine predominantly lambda Bence Jones protein, and only small amounts of IgA paraprotein. Analytical ultracentrifugation of the isolated serum IgA protein showed 7.0S and 4.5S protein peaks but no IgA polymers. When the 7.0S and 4.5S protein peaks were tested with an antiserum specific for alpha chain, both fractions were antigenically deficient compared to control IgA myeloma proteins but showed a line of identity to their F(ab')2 fragments. The serum and 7.0S protein fraction showed double precipitin lines in IgA radial immunodiffusion plates and in immunoelectrophoretic analysis, one line being formed by the myeloma protein and the other by residual normal IgA. The myeloma protein did not form a precipitin line with antisera specific for the IgA Fc fragment. Sodium dodecylsulfate-urea-polyacrylamide gel electrophoresis demonstrated that both the 7.0S and 4.5S fractions of the myeloma protein consisted of covalently linked heavy and light chains, 4.5S fraction being apparently the half-molecule of the 7.0S protein. The heavy chain had a mol wt of 46,500 daltons compared to 55,000 daltons for normal alpha chains. Reduction and alkylation in aqueous solutions resulted in dissociation of the 7.0S myeloma protein fractions into smaller units, probably half-molecules, suggesting that the noncovalent interactions between the alpha chains were substantially weakened or absent, presumably as a result of a deletion in the Fc portion of the alpha chain. The catabolic rates of the radio-labeled 7.0S and 4.5S protein in rhesus monkeys were similar to those of control IgA myeloma proteins; the excretion of protein-bound radioactivity of the IgA half-molecules into the urine was no greater than that of the 7.0S or of control IgA myeloma proteins. It is suggested that the myeloma IgA half-molecule is probably derived from an IgAl mutant that is carried in the human genome and that it is unlikely a representative of a rare IgA subclass or an IgA l allotypic variant.
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PMID:Human myeloma IgA half-molecules. 99 44

Physical and chemical characteristics of the abnormal immunoglobulin as well as the immunoglobulin type are important determinants of the clinical features and prognosis in myeloma. A review of 270 cases of myeloma studied by the Acute Leukemia Group B showed that survival was adversely affected by azotemia. The presence of Bence Jones proteinuria adversely influenced survival even in patients who were not initially azotemic. The presence of lambda-type Bence Jones proteinuria resulted in greatly shortened survival in contrast to kappa-type Bence Jones proteinuria in the absence, or presence, of a serum IgG M-protein. The adverse effect of lambda-type Bence Jones protein could not be demonstrated in patients with IgA myeloma. Patients with IgA myeloma were found to have a noticeably shorter survival than those with IgG myeloma.
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PMID:Correlation of abnormal immunoglobulin with clinical features of myeloma. 111 70

Immunological studies were performed on patients with multiple myeloma. A defect in polymorphonuclear leucocyte (PMN) function as evidenced by diminished adherence of these cells to nylon fibre columns was detected in 16, and low levels of the fourth component of complement (C4) were observed in 14, of the 26 patients studied. Twelve of the patients with low C4 exhibited the defect in PMN adhesiveness whereas only four of the 12 patients with normal C4 showed the defect. The PMN defect was not caused solely by the low C4, since PMNs from seven patients with hereditary angioedema, which is associated with low levels of C4, did not show the defect. The low C4 and defect in PMN adhesiveness occurred primarily in patients with IgG myeloma; all but one of the patients with IgA myeloma, macroglobulinaemia, or light chain disease were normal in both parameters. Results of skin window studies indicated that patients with the PMN defect also had a defect in the early PMN inflammatory response. The defect in PMN adhesiveness could be completely corrected by incubating the cells in normal plasma. Binding of the C4 to paraprotein could not be demonstrated, and C1 activation was found to be caused only by one of 10 isolated paraproteins studied. These studies indicate that patients with paraproteinaemia have immunological abnormalities in addition to low immunoglobulin levels and suggest that these abnormalities may be involved in the pathogenesis of the recurrent infections commonly associated with this disease.
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PMID:Phagocytes and C4 in paraproteinaemia. 119 49

The clinical manifestation fo IgA multiple myeloma are usually not considered distinguishable from those of IgG myeloma despite the fact that IgA differs from IgG in several characteristics, particularly molecular size heterogeneity. The clinical and laboratory features of 25 patients with IgA myeloma seen during a 5 year period are presented. The degree of paraprotein polymerization was observed to vary greatly in these patients but remained chronologically constant in six individuals studied on several occasions over this period. The patients were divided into two groups on the basis of the degree of paraprotein polymerization. The first group comprised those patients in whom the IgA paraprotein was greater than 50% polymerized, whilst in the second group the paraprotein was predominantly monomeric. No clinical or pathological differences were seen between the 'polymeric' and 'monomeric' groups of myeloma apart from that directly attributable to the physicochemical effect of the paraprotein polymerization. Thus, five patients out of 11 of the 'polymeric' group had developed the hyperviscosity syndrome, whilst no patients in the 'monomeric' group had developed this complication. The concentration of the paraprotein during the course of the disease was comparable in both groups. This syndrome is considered to be relatively common in IgA myeloma and adds to the morbidity and mortality of the disease. Its anticipation and treatment may improve the quality and survival of patients likely to develop this complication.
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PMID:Relationship between paraprotein polymerization and clinical features in IgA myeloma. 126 86

An inhibition enzyme-linked immunoassay technique using commercially available antibodies has been developed for the quantitation of both kappa and lambda light chains in the serum of patients with B-cell malignancies. Assay conditions were selected to enable measurement of free light chains in the concentration range between 0.1 and 20 mg/l. The normal range for free lambda chains in serum was found to be 0.4-4.2 mg/l and for free kappa chains it was 1.6-15.2 mg/l. At diagnosis the serum of most patients with multiple myeloma contained increased levels of the malignant free light chain and in some cases there was also elevation of the non-malignant light chain. The absolute level of the malignant light chain at diagnosis did not correlate with survival nor with laboratory parameters such as IgM or creatinine. A correlation with beta 2 M and serum paraprotein levels was evident only in cases of IgA myeloma. Although the absolute level of free serum light chain had no value as a prognostic indicator, the ratio of kappa:lambda chains closely followed the clinical assessment of disease status, being near the normal range (1.2-9.1) in plateau phase or stable disease. During periods of progressive disease this ratio ranged from 19 to 460 (n = 14) in patients with kappa myeloma, and 0.0013-0.14 (n = 9) in patients with lambda myeloma. Determination of the ratio of free light chains in the serum may allow effective monitoring and earlier warning of disease progression in patients with multiple myeloma.
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PMID:Measurement of free kappa and lambda chains in serum and the significance of their ratio in patients with multiple myeloma. 164 19

A successful induction of remission in two patients with resistant multiple myeloma using a new combination therapy of modified M-2 protocol and interferon-alpha (IFN-alpha) is described. The first case was a 32-year-old man with K type urinary Bence-Jones protein who became resistant after treatment with melphalan and prednisone (MP protocol). IFN-alpha alone had a marginal response. The modified M-2 protocol proved insufficient. Therefore, IFN-alpha was administered in the interval of M-2 protocol. This combination therapy showed remarkable responses. The second case was a 59-year-old woman with advanced IgA myeloma who was treated with M-2 protocol and became resistant. IFN-alpha alone resulted in a slight response. After addition of IFN-alpha to the modified M-2 protocol, a rapid reduction in the level of serum IgA was found and clinical symptoms including bone pain, anaemia and so on were dramatically improved. No infection and/or intolerable side effects were observed in either case. This combination treatment appears worthy to try in cases of resistant or relapsing myeloma patients.
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PMID:Combination therapy of M2-protocol and interferon-alpha as remission induction in refractory multiple myeloma. 181 63

Serum fructosamine levels in 36 subjects with various types of multiple myeloma and in 64 normal controls were evaluated by means of a Nitroblue tetrazolium colorimetric assay. Only the IgA myeloma group showed significantly raised serum fructosamine values (P less than 0.001). In the IgG myeloma group, which showed a higher mean serum protein concentration, serum fructosamine levels were not significantly different from controls. The study shows that elevated IgA levels do influence serum fructosamine and this effect should be taken into due consideration in order to avoid possible misinterpretations in evaluating this widely used index of glucose metabolism.
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PMID:Influence of serum proteins on fructosamine concentration in multiple myeloma. 181 55

Human colostral IgA and myeloma proteins of both IgA1 and IgA2 subclasses were susceptible to cleavage by Pseudomonas aeruginosa elastase. Detailed analysis of the cleavage products of IgA myeloma proteins revealed complete degradation of Fab with no evidence of intact Fab fragments as intermediate cleavage products. In contrast, both IgA1 and IgA2 proteins were resistant to cleavage by alkaline protease from P. aeruginosa. The susceptibility of human IgA proteins to elastase suggests a mechanism by which P. aeruginosa might evade the potentially protective function of IgA by producing this enzyme.
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PMID:Degradation of IgA proteins by Pseudomonas aeruginosa elastase. 210 56


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