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MeSH Review


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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


Biological context of Hypergammaglobulinemia


Anatomical context of Hypergammaglobulinemia


Gene context of Hypergammaglobulinemia


Analytical, diagnostic and therapeutic context of Hypergammaglobulinemia


  1. Act1, a negative regulator in CD40- and BAFF-mediated B cell survival. Qian, Y., Qin, J., Cui, G., Naramura, M., Snow, E.C., Ware, C.F., Fairchild, R.L., Omori, S.A., Rickert, R.C., Scott, M., Kotzin, B.L., Li, X. Immunity (2004) [Pubmed]
  2. Roles of interferon-gamma and interleukin-4 in murine lupus. Peng, S.L., Moslehi, J., Craft, J. J. Clin. Invest. (1997) [Pubmed]
  3. Increased plasma viscosity as a reason for inappropriate erythropoietin formation. Singh, A., Eckardt, K.U., Zimmermann, A., Götz, K.H., Hamann, M., Ratcliffe, P.J., Kurtz, A., Reinhart, W.H. J. Clin. Invest. (1993) [Pubmed]
  4. T-bet regulates IgG class switching and pathogenic autoantibody production. Peng, S.L., Szabo, S.J., Glimcher, L.H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. Interleukin 4 and gamma-interferon may play a role in the histopathogenesis of peripheral T-cell lymphoma. Ohnishi, K., Ichikawa, A., Kagami, Y., Nagasaka, T., Niwa, T., Hotta, T., Saito, H. Cancer Res. (1990) [Pubmed]
  6. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. Lane, H.C., Masur, H., Edgar, L.C., Whalen, G., Rook, A.H., Fauci, A.S. N. Engl. J. Med. (1983) [Pubmed]
  7. Virally induced modulation of murine IgG antibody subclasses. Coutelier, J.P., van der Logt, J.T., Heessen, F.W., Vink, A., van Snick, J. J. Exp. Med. (1988) [Pubmed]
  8. Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice. Balomenos, D., Rumold, R., Theofilopoulos, A.N. J. Clin. Invest. (1998) [Pubmed]
  9. Single and combined deletions of the NTAL/LAB and LAT adaptors minimally affect B-cell development and function. Wang, Y., Horvath, O., Hamm-Baarke, A., Richelme, M., Grégoire, C., Guinamard, R., Horejsi, V., Angelisova, P., Spicka, J., Schraven, B., Malissen, B., Malissen, M. Mol. Cell. Biol. (2005) [Pubmed]
  10. Natural killer cell activity from hemophiliacs exhibits differential responses to various forms of interferon. Matheson, D.S., Green, B.J., Poon, M.C., Fritzler, M.J., Hoar, D.I., Bowen, T.J. Blood (1986) [Pubmed]
  11. Nutritional factors and autoimmunity. IV. Dietary vitamin A deprivation induces a selective increase in IgM autoantibodies and hypergammaglobulinemia in New Zealand Black mice. Gershwin, M.E., Lentz, D.R., Beach, R.S., Hurley, L.S. J. Immunol. (1984) [Pubmed]
  12. Cell-mediated suppression of the fifth component of complement in mice. Goldman, M.B., French, D.L., Goldman, J.N. J. Immunol. (1979) [Pubmed]
  13. Immune depression and macroglobulinemia in experimental subchronic trypanosomiasis. Baltz, T., Baltz, D., Giroud, C., Pautrizel, R. Infect. Immun. (1981) [Pubmed]
  14. Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance. Sun, H., Chow, M.S., Maderazo, E.G. Antimicrob. Agents Chemother. (1991) [Pubmed]
  15. Effect of cyclosporin A and zidovudine on immune abnormalities observed in the murine acquired immunodeficiency syndrome. Cerny, A., Merino, R., Fossati, L., de Kossodo, S., Heusser, C., Waldvogel, F.A., Morse, H.C., Izui, S. J. Infect. Dis. (1992) [Pubmed]
  16. Beta 2-microglobulin-deficient mice are protected from hypergammaglobulinemia and have defective antibody responses because of increased IgG catabolism. Christianson, G.J., Brooks, W., Vekasi, S., Manolfi, E.A., Niles, J., Roopenian, S.L., Roths, J.B., Rothlein, R., Roopenian, D.C. J. Immunol. (1997) [Pubmed]
  17. Role of cyclin kinase inhibitor p21 in systemic autoimmunity. Santiago-Raber, M.L., Lawson, B.R., Dummer, W., Barnhouse, M., Koundouris, S., Wilson, C.B., Kono, D.H., Theofilopoulos, A.N. J. Immunol. (2001) [Pubmed]
  18. Effects of the motheaten gene on murine B-cell production. McCoy, K.L., Clagett, J., Rosse, C. Exp. Hematol. (1985) [Pubmed]
  19. Immunological follow-up in children born to HIV-1 infected mothers. Garcia Rodriguez, M.C., Omeñaca, F., Ferreira, A., Madero, R., Zapico, R., Muro, M., De José, I., Fontán, G. Acta paediatrica Scandinavica. (1991) [Pubmed]
  20. Circulating immune complexes in eosinophilic fasciitis. Seibold, J.R., Rodnan, G.P., Medsger, T.A., Winkelstein, A. Arthritis Rheum. (1982) [Pubmed]
  21. Autoantibodies to alpha-fodrin in primary Sjögren's syndrome and SLE detected by an in vitro transcription and translation assay. Nordmark, G., Rorsman, F., Rönnblom, L., Cajander, S., Taussig, M.J., Kämpe, O., Winqvist, O. Clinical and experimental rheumatology. (2003) [Pubmed]
  22. Human B cell differentiation induced by microbial superantigens: unselected peripheral blood lymphocytes secrete polyclonal immunoglobulin in response to Mycoplasma arthritidis mitogen. Crow, M.K., Zagon, G., Chu, Z., Ravina, B., Tumang, J.R., Cole, B.C., Friedman, S.M. Autoimmunity (1992) [Pubmed]
  23. Eosinophilic fasciitis in an adolescent girl with lymphadenopathy and vitiligo-like and linear scleroderma-like changes. A case report. Stork, J., Nĕmcová, D., Hoza, J., Kodetová, D. Clinical and experimental rheumatology. (1996) [Pubmed]
  24. Eosinophilic granuloma of the soft tissue in the orbit. Amemiya, T. Ophthalmologica (1981) [Pubmed]
  25. Perforin protects against autoimmunity in lupus-prone mice. Peng, S.L., Moslehi, J., Robert, M.E., Craft, J. J. Immunol. (1998) [Pubmed]
  26. Control of multiple autoantibodies linked with a lupus nephritis susceptibility locus in New Zealand black mice. Vyse, T.J., Rozzo, S.J., Drake, C.G., Izui, S., Kotzin, B.L. J. Immunol. (1997) [Pubmed]
  27. Vitamin E supplementation with interferon-gamma administration retards immune dysfunction during murine retrovirus infection. Wang, J.Y., Liang, B., Watson, R.R. J. Leukoc. Biol. (1995) [Pubmed]
  28. Amelioration of lymphoid hyperplasia and hypergammaglobulinemia in lupus-prone mice (gld) by Fas-ligand gene transfer. Hong, N.M., Masuko-Hongo, K., Sasakawa, H., Kato, T., Shirai, T., Okumura, K., Nishioka, K., Kobata, T. J. Autoimmun. (1998) [Pubmed]
  29. Lymphokine production by B cells from normal and HIV-infected individuals. Kehrl, J.H., Rieckmann, P., Kozlow, E., Fauci, A.S. Ann. N. Y. Acad. Sci. (1992) [Pubmed]
  30. Characteristics of CD4+ T cells which transfer murine AIDS (MAIDS). Donaldson, L.A., Cheng, R., Savage, S.M., Sopori, M.L. Cell. Immunol. (1994) [Pubmed]
  31. Functional analyses of B cells in (NZW x BXSB) F1 mice. Adachi, Y., Inaba, M., Inaba, K., Nagata, N., Kobayashi, Y., Ikehara, S. Autoimmunity (1993) [Pubmed]
  32. Diffuse infiltrating T-cell lymphoma of the colon associated with polyclonal hypergammaglobulinemia and hepatocellular carcinoma: report of a case. Nagai, T., Koyama, R., Sasagawa, Y., Matsumoto, S., Niitsu, Y., Takayama, S., Murakami, T., Matsuura, A. Jpn. J. Med. (1991) [Pubmed]
  33. Acquired chronic pure red cell aplasia successfully treated with intravenous pulse methylprednisolone therapy. Uchiyama, M., Ichikawa, Y., Komatsuda, M., Miyairi, A., Arimori, S. Intern. Med. (1992) [Pubmed]
  34. Hypergammaglobulinemia and erythrocyte autoantibody complicate enzyme immunoassay of antimalarial antibody. Hunter, K.W., Smith, L.P., Strickland, G.T., Blackburn, W.A. Journal of immunoassay. (1981) [Pubmed]
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