Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Immune abnormalities have been found in many patients receiving anti-epileptic drugs. However, the effects of carbamazepine are still conflicting. We report the case of a 31-year-old woman who began carbamazepine treatment because of idiopathic epilepsy of adulthood. After three years of treatment she developed arthralgias and malaise. Complete immunologic evaluation showed a total absence of immunoglobulin M with decreased levels of immunoglobulin A, positive antinuclear antibodies and monoclonal paraproteinemia type IgG-kappa. The possibility of B cell lymphoma or myeloma was ruled out. Skin testing was negative. Bone marrow examination was normal. After carbamazepine discontinuation, levels of IgA and IgM increased until reaching normal values over 3 years. The monoclonal gammopathy of undetermined significance also disappeared over this period. During this period of immunodeficiency, the patient did not complain of any infectious complications.
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PMID:Carbamazepine induced transient monoclonal gammopathy and immunodeficiency. 1508 96

The age-adjusted prevalence rate of monoclonal gammopathy of undetermined significance (MGUS) is three-fold higher in African Americans than whites. Similarly, there is a higher preponderance of multiple myeloma (MM) in African-American patients. Since the risk of progression of MGUS to MM is equal in both races, identification of exogenous and genetic risk factors of MGUS [such as genetic pre-disposition; diet; and chronic antigenic exposure related to sexually transmitted diseases, including human immunodeficiency virus (HIV) infection] is essential for unraveling the etiology of the racial disparity for MM. HIV infection, a well-documented risk factor for MGUS, is more frequent in African-American patients. Future epidemiologic studies dealing with plasma cell disorders should carefully examine the relationship between race, HIV infection status, prevalence of MGUS and its ultimate progression to MM.
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PMID:Higher prevalence of monoclonal gammopathy of undetermined significance in African Americans than whites--the unknown role of underlying HIV infection. 1712 99

Hypogammaglobulinemia of the non-monoclonal immunoglobulin heavy chain classes has been reported in monoclonal gammopathy of undetermined significance (MGUS) patients. Whether low polyclonal immunoglobulin levels are associated with impaired specific antibody production and whether they represent a risk factor for the development of recurrent bacterial infections have not been established in this population. We determined the frequency of MGUS in patients referred to a tertiary care clinical immunology ambulatory care practice for evaluation of hypogammaglobulinemia, who were assessed for deficits in specific antibody production and the presence of recurrent infections. Of the 133 patients evaluated for hypogammaglobulinemia, 68 were screened for monoclonal gammopathy and 5 were found to have MGUS. Three had MGUS associated hypogammaglobulinemia in the absence of a defining primary immunodeficiency, one possibly had common variable immunodeficiency, and one had an uncertain diagnosis. Thus, MGUS may be uncovered in patients presenting with hypogammaglobulinemia even in those who lack an elevated serum level of IgG, IgM, or IgA.
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PMID:The relationship between hypogammaglobulinemia, monoclonal gammopathy of undetermined significance and humoral immunodeficiency: a case series. 2164 91

Characterised by the association of a thymoma, hypogammaglobulinaemia, and B-cell and T-cell dysfunction, Good's syndrome (GS) is a rare cause of adult immunodeficiency leading to recurrent infections, and autoimmune manifestations related to the thymoma. We describe a 70-year-old woman in whom the diagnosis of GS was made after 7 years follow-up of a monoclonal gammopathy of undetermined significance (MGUS). After thymectomy, she received monthly intravenous immunoglobulin perfusions in order to maintain a normal plasmatic IgG level. To our knowledge, this is the fifth described case of GS associated with an MGUS. This rare condition should not be misdiagnosed, as the prognosis is determined by infectious and autoimmune complications, which could be prevented.
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PMID:Good's syndrome and IgA monoclonal gammopathy of undetermined significance. 2318 74

The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin's lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin's lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they seem to be safe and highly effective. The use of chemotherapy in combination with rituximab for the treatment of BCNHL in patients infected with HCV can produce liver dysfunction. The addition of immunotherapy with rituximab can increase the viral replication, and severe complications can occure especially in patients co-infected with hepatitis B virus or immune immunodeficiency virus, in those with hepatocarcinoma, cirrhosis, or liver cytolysis. But the final result of standard immunochemotherapy applied to diffuse large BCNHL patients with HCV infection is not notably worse than in those without this viral infection. The treatment of patients chronically infected with HCV and having BCNHL is complex and requires a multidisciplinary approach and the risk / benefit ratio of rituximab treatment must be evaluated especially in those with liver cytolysis.
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PMID:Hepatitis C virus - associated B cell non-Hodgkin's lymphoma. 2746 11

Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are prone to present with antibody production deficits associated with recurrent or severe bacterial infections that might benefit from human immunoglobulin (Ig) (IVIg/SCIg) replacement therapy. However, the original IVIg trial data were done before modern therapies were available, and the current indications do not take into account the shift in the immune situation of current treatment combinations and changes in the spectrum of infections. Besides, patients affected by other B cell malignancies present with similar immunodeficiency and manifestations while they are not covered by the current IVIg indications. A potential beneficial strategy could be to vaccinate patients at monoclonal B lymphocytosis and monoclonal gammopathy of undetermined significance stages (for CLL and MM, respectively) or at B-cell malignancy diagnosis, when better antibody responses are attained. We have to re-emphasize the need for assessing and monitoring specific antibody responses; these are warranted to select adequately those patients for whom early intervention with prophylactic anti-infective therapy and/or IVIg is preferred. This review provides an overview of the current scenario, with a focus on prevention of infection in patients with hematological malignancies and the role of Ig replacement therapy.
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PMID:Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy. 2759 52

An active role for the immune system in controlling the malignant plasma cell clone in myeloma has been postulated for many years. The clinical states of monoclonal gammopathy of undetermined significance, plateau phase disease, and smoldering myeloma all suggest that a significant host-tumor interaction is taking place. The fundamental role of the cytotoxic T cell in tumor elimination and control has been exemplified by the dramatic efficacy of adoptive T-cell therapies in many hemopoietic malignancies. However, tumor-host cross-talk results in suppression of the endogenous cytotoxic T-cell response against the malignant plasma cell. Whereas patients with myeloma do not clinically exhibit a T-cell immunodeficiency state, with, for example, increased mycobacterial infections, a number of abnormalities of T-cell function are evident. The major abnormalities of T cells include clonal expansions and associated immunosenescence, alterations of regulatory T cells/T helper 17 cells (Treg/Th17 ratio) and acquired membrane abnormalities, due to trogocytosis, which result in acquired Treg cells. Dendritic cell dysfunction associated with impaired antigen processing and presentation caused by abnormalities of the bone marrow microenvironment plays an additional role. In this perspective, we examine the T-cell abnormalities in myeloma and postulate that, whereas cytotoxic T cells interacting with the tumor are dysfunctional, residual T cells still function adequately against external pathogens and thus protect patients from the infections normally associated with a generalized T-cell immunodeficiency state. The so-called 3 E's of host-tumor interaction (elimination, equilibrium, and escape) are clearly reflected in the immune landscape and clinical behavior of myeloma.
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PMID:The T Cell in Myeloma. 2760 Oct 1


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