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)

A series of suppressor cell systems regulate virtually all immunologic processes. Disorders of these systems have been identified in association with a number of diseases. An abnormal number of activated suppressor T-cells have been seen in some patients with common variable hypogammaglobulinemia and in some with selective IgA deficiency. Suppressor T-cells that inhibit immunoglobulin synthesis also develop in an animal model of immunodeficiency, the agammaglobulinemia of the bursectomized bird. Non-T-cell suppressor cells are a pathogenic factor in the humoral immunodeficiency associated with multiple myeloma. At the other end of the spectrum of immunologic response, a reduction in functional activity of suppressor T-cells has been implicated in the pathogenesis of autoimmune diseases. The disorders of suppressor cells that have been shown in immunodeficiency and autoimmunity are important when developing rational strategies for prevention and therapy of these immunologic disorders.
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PMID:Disorders of suppressor immunoregulatory cells in the pathogenesis of immunodeficiency and autoimmunity. 30 22

Human sera of different categories were screened for antibodies against IgA. A surprisingly high incidence of antibodies was observed. All of these antibodies were of restricted specificity, i.e. able to react with one or a few individual IgAs from a panel of eight myeloma proteins used in the screening. In one serum of a patient with selective IgA deficiency an antibody against the allotype A2m(1) was found. Some of the antibodies were shown to belong to the IgG class. The IgA, IgG and IgM content of the antibody-containing sera was generally increased. Two different antibodies which both reacted with the same individual IgA were studied in detail. The antigen involved could not be detected in normal Caucasian sera but was detectable in some sera of patients with IgA, IgG, IgM or IgD paraproteinemia. The antigenic site was located on the light chain of the Ig molecule but no correlation with either the light chain type or the genetically determined Inv factor was evident.
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PMID:Naturally occurring human antibodies with specificity for light chains of immunoglobulins. 40 78

Pyoderma gangrenosum (PG) is a rare condition remarkable for its association with particular diseases, notably haemopathies and gastrointestinal diseases. As regards haemopathies, the associations most frequently encountered are with myeloid malignancies and monoclonal dysglobulinaemia. The association of PG with mainly inflammatory digestive tract diseases is also classical. The lack of publications concerning gastric atrophy and the dual haematological and gastric pathology which characterizes our case have prompted us to report it. A 60-year-old woman without significant history was admitted for PG on both knees, following vesiculo-bullous lesions. Laboratory examinations detected a normochromic anaemia tending to be macrocytic, a marked inflammatory syndrome and a monoclonal lambda light chain IgA peak at protein immunoelectrophoresis. Bone marrow biopsy, skeletal radiography and a search for Bence-Jones proteinuria were normal or negative. Colonoscopy showed no abnormality, but fibroscopy of the upper digestive tract revealed a severe gastric atrophy en plaques. Serum vitamin B12 level was moderately low, but there was no other sign of pernicious anaemia. After one month treatment with systemic corticosteroids, healing was obtained under replacement vitamin therapy. PG recurred a few months later; serum vitamin B12 level was normal, and the lesions healed after systemic corticosteroid treatment. In non-myelomatous dysglobulinaemia IgA is frequently found and there is no light chain predominance. PG often precedes dysglobulinaemia. Evolution towards a true myeloma seems to be exceptional. In a recent publication, 17 cases of association between PG and myeloma were mentioned, the IgA type being most common. Protein electrophoresis is indispensable in patients with PG. Five cases of congenital hypogammaglobulinaemia have been recorded, including three with IgA deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pyoderma gangrenosum and IgA gammopathy. Association with atrophic gastritis]. 251 19

Immune defense mechanisms play an essential protective role against infections caused by a wide array of pathogenic microorganisms. Although the growing number of the available antimicrobial agents has certainly improved the overall clinical outcome of such infections, antimicrobial therapy not rarely fails whenever the host's immune function is depressed. On the other hand, recently introduced therapeutic and diagnostic procedures (antineoplastic chemotherapy causing severe neutropenia and mucositis; organ transplantation requiring conditioning regimens; the widespread use of intravascular catheters and prosthetic devices; administration of adrenal corticosteroids and/or other immunosuppressive agents) have resulted in an unprecedented number of immunocompromised hosts. In addition, a variety of antibiotics have been found to display adverse effects on specific and non-specific immune functions, thus further impairing the already depressed immune system of the host. Antibiotic-mediated immunomodulation hence is explored with the introduction of a third-generation cephalosporin, namely cefodizime (CDZ), which has been shown to possess immunostimulating properties in preliminary in vitro and ex vivo studies as well as in a few experimental animal models. A chronoimmunopharmacological approach to CDZ-induced immunomodulation has been started by ourselves. The study, which is still in progress, includes patients with multiple myeloma (MM), selective IgA deficiency and chronic uremia, and matched healthy subjects. A number of immunological parameters are being assessed on blood samples drawn every 6h in the 24-h span prior to CDZ administration (a single 2 g daily dose i.v. for 6 days to the patients and for 4 days to healthy subjects), and in the 24h following the last CDZ injection. Healthy subjects and patients are randomly assigned to two groups, depending on whether they are given the antibiotic at 0800 or at 1800. Although a full evaluation of the results will be reported elsewhere, the group of MM now includes 24 patients. A circadian stage-dependent chronoimmunomodulating effect has been unequivocally shown for the monocytic chemotactic responsiveness to CDZ in MM. Immunostimulating 'side-effects' suggest that CDZ should possibly be regarded as a prototype antimicrobial agent for patients with impaired immune functions. Conceivably, a better knowledge of such properties will help synthesize new antibiotics with specific immunomodulating effects.
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PMID:Antimicrobial agents as biological response modifiers (BRM) and chrono-immunomodulation: an emerging relationship. 304 51

IgG and IgM isotype antibodies to polyclonal human IgA, myeloma IgA1, and myeloma IgA2 were estimated in 38 IgA-deficient children aged between 0.9 and 15 years. All children had IgM anti-IgA antibodies. IgG antibodies against either polyclonal IgA, IgA1, or IgA2 were present in 63% of the IgA-deficient children. IgG anti-IgA antibodies were detected against all three antigens in 8 of 11 severely IgA-deficient children and in 7 of 27 partially IgA-deficient children, but in only 1 of 23 healthy adult controls. The proportion of children with IgG anti-IgA antibodies was significantly greater in the severely IgA-deficient group in comparison with the partially IgA-deficient group and the adult controls (chi-square test, P less than 0.01 and P less than 0.005, respectively). There was a strong correlation within each IgG subclass between antibody responses toward each of the three IgA antigens. Twenty-four children were followed over a period ranging from 0.9 to 11 years (mean, 2.3 years). Three children who were initially IgG anti-IgA antibody negative became antibody positive and three who were antibody positive became antibody negative. Five children with severe IgA deficiency remained severely IgA deficient and IgG antibodies to IgA persisted in all five at follow-up. The presence of IgG anti-IgA antibodies did not influence the normalization of serum IgA at follow-up in 14 of 19 children who were initially partially IgA deficient.
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PMID:Anti-IgA antibodies in IgA-deficient children. 326 81

To study the expression of FcR specific for IgA (Fc alpha R) on human peripheral lymphocytes (PBL), PBL from normal donors were incubated with 300 to 500 micrograms/ml MOPC 315 IgA having anti-trinitrophenyl (TNP) antibody activity at 4 degrees C or 37 degrees C for 60 min. Under this condition, less than 2% of total cells could form rosettes with TNP-coated ox red blood cells (TNP-ORBC). When cultured with MOPC 315 IgA at 37 degrees C for 18 hr, however, there was a dose-dependent increase of the rosette-forming cells (RFC) binding TNP-ORBC. Because 15 to 20% of the total cells bound TNP-ORBC but not unsensitized ORBC, the rosette formation appeared to be due to the cytophilic binding of IgA to the cells. The binding of MOPC 315 IgA was competed by TEPC 15 IgA and human myeloma IgA, but not by murine myeloma proteins of other classes, indicating that the receptor is specific for IgA. Fc alpha R was induced on 15 to 20% of fractionated T and B cells, as well as on 15 to 18% of concanavalin A-(Con A) activated lymphocytes when cultured with IgA. The induction of the receptor was dependent on protein and RNA synthesis, but not on DNA synthesis as suggested by the sensitivity to metabolic inhibitors, such as mitomycin C, actinomycin D, puromycin, and cycloheximide. In five patients with selective IgA deficiency (serum IgA, 0 to 4 mg/dl), only 5.1% +/- 1.7 of PBL formed rosettes with TNP-ORBC after culture with MOPC 315 IgA, whereas 12.5% +/- 2.5 of PBL from normal donors (serum IgA, 90 to 330 mg/dl) formed rosettes. Fc alpha R was induced on more than 15% of the cells from these patients, however, when cultured with IgA in the presence of a conditioned medium obtained from mixed lymphocyte culture from two normal donors. The results suggested that the abnormality in the patients' PBL might be in the induction mechanism rather than in the number of precursor cells that could express Fc alpha R in the presence of IgA. On the other hand, Fc alpha R was induced on 10.4% +/- 1.5 of PBL from the patients with IgA nephropathy (serum IgA, 382 +/- 11 mg/dl) when they were incubated with IgA for 1 hr at 37 degrees C. Because Fc alpha R on normal PBL was not induced by 1 hr of incubation with IgA, it appeared that the receptor was already expressed in vivo on the cells of these patients.
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PMID:Altered expression of lymphocyte Fc alpha receptor in selective IgA deficiency and IgA nephropathy. 622 55

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

IgA anaphylactic transfusion reactions are rare events, estimated to occur in 1 in 20,000 to 47,000 transfusions. The signs and symptoms of these reactions do not differentiate them from other causes of anaphylaxis. The diagnosis of an anaphylactic transfusion reaction is established by showing an IgA-antibody in the patient's serum. Most laboratories that test for IgA antibodies rely on the PHA method, which uses red blood cells that are coated with serologically defined IgA multiple myeloma proteins. We tested sera referred from Red Cross regional blood centers and hospitals from patients with suspected IgA anaphylactic reactions and found an IgA antibody in 76.3% of IgA-deficient patients. However, only 17.5% of all samples referred contained an IgA antibody, indicating that most persons with suspected IgA anaphylactic reactions had experienced acute generalized reactions that were from causes other than anti-IgA transfusion. Using PHIA to measure serum concentrations of IgA and PHA to detect IgA antibodies, we found the frequency of IgA deficiency (< 0.05 mg/dL) and class-specific anti-IgA in random blood donors to be approximately 1 in 1,200. Titers of anti-IgA did not distinguish these seemingly healthy blood donors from patients with a history of an anaphylactic transfusion reaction. Because the frequency of 1 in 1,200 greatly exceeds the observed frequency of anaphylactic reactions in transfused persons, we conclude that using PHA for anti-IgA does not reliably predict risk for an anaphylactic transfusion reaction. Additional research is needed to define a more specific marker to identify those persons who are truly at risk for these serious, but rare, complications of blood transfusion.
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PMID:IgA anaphylactic transfusion reactions. 771 37

A total of 734 serum specimens from various clinical disorders along with 100 control samples from healthy subjects were processed for estimation of serum IgG, IgA and IgM employing single radial immunodiffusion procedure. Immunoglobulin deficiency, either selective or combined was noted in 31 males and 24 females in all age groups. Of the 55 cases encountered it was secondary immunoglobulin deficiency which was seen on a larger scale and encountered in patients with Multiple myeloma (16 out of 32) followed by Leprosy (14 out of 250), Lymphoma (5 out of 43), Malaria (4 out of 137), Burns (4 out of 52), Rheumatoid arthritis (2 out of 69) and non lymphoreticular malignancies (1 out of 41) in decreasing order of frequency. Primary immunoglobulin deficiency was observed in nine cases comprising of six belonging to Idiopathic late onset immunoglobulin deficiency, two of dysgammaglobulineamia and a solitary case of Ataxia telangiectasia. Panimmunoglobulin deficiency was observed in six cases, 11 had a dual deficiency while 38 showed deficiency of an isolated class with selective IgA deficiency in 20 cases. Furthermore, one patient each had total absence of IgG or IgA while IgM was not detectable in seven patients. A high suspicion index along with a regular rapport between the clinician and the laboratory personnel is necessary in the diagnostic set up of immunoglobulin deficiency states.
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PMID:Analysis of immunoglobulin deficiency cases: a five year study. 935 99

A patient with multiple myeloma was noted to have an IgA deficiency during investigation of a possible transfusion reaction due to IgA deficiency and anti-IgA. Because of the patient's age, otherwise good health, and early stage of disease, he was enrolled in a research treatment protocol that involved an allogeneic bone marrow transplant (BMT). The BMT successfully put the patient in complete remission from his multiple myeloma and corrected his IgA deficiency. Class-specific IgG anti-IgA antibody that had been identified prior to BMT was no longer detectable in his plasma. Anaphylactic transfusion reactions were successfully avoided by using a combination of IgA-deficient and washed blood components including the marrow graft, and IgA-reduced intravenous immunoglobulin.
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PMID:Transfusion management of an IgA deficient patient with anti-IgA and incidental correction of IgA deficiency after allogeneic bone marrow transplantation. 954 78


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