Disease relevance of Hypergammaglobulinemia

• Genetic deficiency in a novel adaptor molecule, Act1, for CD40 and BAFF results in a dramatic increase in peripheral B cells, which culminates in lymphadenopathy and splenomegaly, hypergammaglobulinemia, and autoantibodies [1].
• These results suggest that IFN-gamma and IL-4 play opposing but dispensable roles in the development of lupus-associated hypergammaglobulinemia and autoantibody production; however, they both play prominent roles in the pathogenesis of murine lupus-associated tissue injury, as well as in lpr-induced lymphadenopathy [2].
• The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease [3].
• This function contributes critically to the pathogenesis of murine lupus, where the absence of T-bet strikingly reduces B cell-dependent manifestations, including autoantibody production, hypergammaglobulinemia, and immune-complex renal disease and, in particular, abrogates IFN-gamma-mediated IgG2a production [4].
• Thus, IL-4 may play an important role in the development of hypergammaglobulinemia as well as in the growth and histopathogenesis of T-cell lymphoma, and gamma-interferon may be responsible for the development of Lennert's lesion [5].

High impact information on Hypergammaglobulinemia

• The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients [6].
• The results indicate that when a hypergammaglobulinemia was induced by the infection, it was restricted to the IgG2a and, to a lesser extent, to the IgG2b subclasses [7].
• Hypergammaglobulinemia was maintained with a switch from IgG2a to IgG1 predominance, but the dramatic decrease in levels of the dominant IgG2a anti-dsDNA autoantibodies was not associated with a compensatory increase in TH2-associated IgG subclasses [8].
• Although NTAL is also expressed in plasma cells, its absence did not affect the hypergammaglobulinemia E and G1 that developed in mice with a mutation in tyrosine 136 of LAT [9].
• Patients with AIDS have recurrent infections and/or malignancy and altered immune response, including decreased T lymphocyte counts, decreased T helper lymphocytes, defective T cell blastogenesis, hypergammaglobulinemia, defective natural killer (NK) activity and impaired response of NK to interferon-beta (IFN-beta) [10].

Chemical compound and disease context of Hypergammaglobulinemia

• Nutritional factors and autoimmunity. IV. Dietary vitamin A deprivation induces a selective increase in IgM autoantibodies and hypergammaglobulinemia in New Zealand Black mice [11].
• When there was a concurrent chronic GVH reaction induced by lymphoid cells administered to offspring of H-2 incompatible parents, there was usually a resultant hypergammaglobulinemia that was also unrelated to the presence or absence of C5 suppression [12].
• Hypergammaglobulinemia was also induced in relapsing T. equiperdum-infected mice treated with Berenil [13].
• Simulations with the model indicated that patients with hypergammaglobulinemia have an increased potential of being exposed to prolonged subinhibitory concentrations of ceftriaxone if the drug is given once every 24 h [14].
• First, a low dose of cyclosporin A (20 mg/kg/day) was ineffective, and treatment initiated 5 days after infection did not protect against virus-induced lymphoproliferation and hypergammaglobulinemia [15].

Biological context of Hypergammaglobulinemia

• Beta 2-microglobulin-deficient mice are protected from hypergammaglobulinemia and have defective antibody responses because of increased IgG catabolism [16].
• Here, we report that mixed background p21-deficient 129/Sv x C57BL/6 mice showed increased in vitro and in vivo T cell cycling and activation, moderate hypergammaglobulinemia and, at low penetrance, anti-chromatin autoantibodies [17].
• The rapidly fatal autoimmune disease in the mutant mouse known as motheaten is caused by an autosomal recessive gene and is characterized by hypergammaglobulinemia and autoantibody production, among other defects [18].
• Most of the HIV-1 infected babies showed early abnormalities in humoral and cellular immunity, hypergammaglobulinemia, low percentage of CD4 circulating lymphocytes and increased spontaneous in vitro immunoglobulin production [19].

Anatomical context of Hypergammaglobulinemia

• Elevated levels by Raji cell assay were present more frequently at times of active disease [17 of 22 sera (77%)] than at times of inactive disease [2 of 24 (8%) (P less than 0.0005)] and were more closely correlated with disease activity than were eosinophilia, hypergammaglobulinemia, or increased erythrocyte sedimentation rate [20].
• Correlations to RF, ANA, anti-dsDNA, anti-SS-A and anti-SS-B antibodies, hypergammaglobulinemia, labial salivary gland biopsy grade, extraglandular manifestations and a modified SLE disease activity index (mSLEDAI) were made [21].
• MAM-like SA, when encountered in vivo, may result in a significant perturbation of the human immune system and potentially contribute to clinical syndromes characterized by immunostimulation and hypergammaglobulinemia [22].
• Two months later she developed edema of the left lower extremity, finger flexion contractures and induration of the skin of the left leg, associated with hypergammaglobulinemia, peripheral hypereosinophilia, elevated ESR and a positivity of ANA and anti ds-DNA antibodies [23].
• The clinical characteristics were typical for eosinophilic granuloma of the soft tissue: 8% eosinophils, very soft tumor masses in both orbits, multifocal lesions including the salivary glands, good response to steroid hormone, and hypergammaglobulinemia [24].

Gene context of Hypergammaglobulinemia

• Perforin-deficient Fas+ animals developed accelerated autoimmunity, characterized by increased hypergammaglobulinemia, autoantibody production, and immune deposit-related end-organ disease compared with perforin-intact counterparts [25].
• Nba2 was also linked (or showed a trend for linkage) with hypergammaglobulinemia and IgG1, IgG2a, and/or IgG3 levels in each backcross [26].
• The treatment also prevented loss of Th1 cytokine (IL-2 and IFN-gamma) secretion by splenocytes from retrovirus-infected mice alleviating splenomegaly and hypergammaglobulinemia [27].
• Amelioration of lymphoid hyperplasia and hypergammaglobulinemia in lupus-prone mice (gld) by Fas-ligand gene transfer [28].
• Ig production by normal in vitro-activated B cells and freshly isolated B cells from patients with hypergammaglobulinemia is largely dependent upon TNF-alpha and IL-6 production [29].

Analytical, diagnostic and therapeutic context of Hypergammaglobulinemia

• The disease is characterized by hypergammaglobulinemia, polyclonal B cell activation, lymphadenopathy, and generalized immunosuppression within 5-8 weeks postinfection [30].
• The W/BF1 mouse, which is an animal model for systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP), produces anti-DNA and anti-platelet antibodies; W/BF1 mice show hypergammaglobulinemia (particularly increases in IgG2a and IgG2b) [31].
• Chemotherapy with cyclophosphamide, vincristine and prednisolone (VEP regimen) was effective for mucosal bleeding of the colonic lesion and reduction of polyclonal hypergammaglobulinemia [32].
• A 65-year-old male patient developed acquired chronic pure red cell aplasia (PRCA) associated with hypergammaglobulinemia and positive Coombs' test during the treatment of eosinophilic pneumonia with prednisolone (PSL) [33].
• Enzyme immunoassay of specific antimalarial antibody in sera from Plasmodium yoelii-infected mice was complicated by hypergammaglobulinemia and erythrocyte (RBC) autoantibody [34].

References