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Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 1/2008

01-05-2008

Autoimmunity in Common Variable Immunodeficiency

Authors: Susana Lopes-da-Silva, Luiz Vicente Rizzo

Published in: Journal of Clinical Immunology | Special Issue 1/2008

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Abstract

Background

Autoimmunity has been increasingly recognized as a major issue in patients with common variable immunodeficiency (CVID), the most common symptomatic primary immunodeficiency in adulthood. Different authors report high prevalences of autoimmune diseases in CVID, and several mechanisms have been proposed to explain this apparent paradox. Genetic predisposition, under current surveillance, innate and adaptive immunity deficiencies leading to persistent/recurrent infections, variable degrees of immune dysregulation, and possible failure in central and peripheral mechanisms of tolerance induction or maintenance may all contribute to increased autoimmunity.

Conclusions

Data on the clinical/immunological profile of affected patients and treatment are available mostly concerning autoimmune cytopenias, the most common autoimmune diseases in CVID. Treatment is based on conventional alternatives, in association with short experience with new agents, including rituximab and infliximab. Benefits of early immunoglobulin substitutive treatment and hypothetical premature predictors of autoimmunity are discussed as potential improvements to CVID patients’ follow-up.
Literature
1.
Bayry J, Hermine O, Webster DA, Levy Y, Kaveri SV. Common variable immunodeficiency: the immune system in chaos. Trends Mol Med 2005;11:370–6.PubMedCrossRef
2.
Pavic M, Sève P, Malcus C, Sarrot-Reynault F, Peyramond D, Debourdeau P, Andriamanantena D, Bouhour D, Philippe N, Rousset H, Broussolle C. Common variable immunodeficiency with autoimmune manifestations: study of nine cases; interest of a peripheral B-cell compartment analysis in seven patients. Rev Med Interne 2005;26:95–102.PubMed
3.
Bloch-Michel C, Viallard JF, Blanco P, Bloch Liferman F, Neau D, Moreau JF, Baillet L, Etienne G, Longy-Boursier M, Pellegrin JL. Common variable immunodeficiency: 17 observations in the adult. Rev Med Interne 2003;24:640–50.PubMedCrossRef
4.
Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarström L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol 2007;120:776–94.PubMedCrossRef
5.
Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun 2005;25:57–62.PubMedCrossRef
6.
Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol 2004;114:415–21.PubMedCrossRef
7.
Kokron CM, Errante PR, Toledo-Barros M, Baracho GV, Camargo MM, Kalil J, Rizzo LV. Clinical and laboratory aspects of common variable immunodeficiency. An Acad Bras Ciênc 2004;76:1–20.CrossRef
8.
Cunnigham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 1999;92:34–48.CrossRef
9.
Warnatz K, Wehr C, Dräger R, Schmidt S, Eibel H, Schlesier M, Peter HH. Expansion of CD19hiCD21lo/neg B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology 2002;206:502–13.PubMedCrossRef
10.
Sarmiento E, Mora R, Rodríguez-Mahou M, Rodríguez-Molina J, Fernández-Cruz E, Carbone J. Autoimmune disease in primary antibody deficiencies. Allergol Immunopathol 2005;33:69–73.CrossRef
11.
Salzer U, Maul-Pavicic A, Cunningham-Rundles C, Urschel S, Belohradsky BH, Litzman J, Holm A, Franco JL, Plebani A, Hammarstrom L, Skrabl A, Schwinger W, Grimbacher B. ICOS deficiency in patients with common variable immunodeficiency. Clin Immunol 2004;113:234–40.PubMedCrossRef
12.
Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, Claudio P, Franco D, Maria Pesce A, Borghese F, Guerra A, Rondelli R, Plebani A. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. Clin Immunol 2007;27:308–16.CrossRef
13.
Detková D, de Gracia J, Lopes-da-Silva S, Vendrell M, Alvarez A, Guarner L, Vidaller A, Rodrigo MJ, Caragol I, Espanol T, Hernández M. Common variable immunodeficiency: association between memory B cells and lung diseases. Chest 2007;131:1883–9.PubMedCrossRef
14.
15.
Michel M, Chanet V, Galicier L, Ruivard M, Levy Y, Hermine O, Oksenhendler E, Schaeffer A, Bierling P, Godeau B. Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature. Medicine 2004;83:254–63.PubMedCrossRef
16.
George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, Blanchette VS, Bussel JB, Cines DB, Kelton JG, Lichtin AE, McMillan R, Okerbloom JA, Regan DH, Warrier I. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996;88:3–40.PubMed
17.
18.
Giannouli S, Anagnostou D, Soliotis F, Voulgarelis M. Autoimmune manifestations in common variable immunodeficiency. Clin Rheumatol 2004;23:449–52.PubMedCrossRef
19.
Swierkot J, Lewandowicz-Uszynska A, Chlebicki A, Szmyrka-Kaczmarek M, Polańska B, Jankowski A, Szechinski J. Rheumatoid arthritis in a patient with common variable immunodeficiency: difficulty in diagnosis and therapy. Clin Rheumatol 2006;25:92–4.PubMedCrossRef
20.
Sordet C, Cantagrel A, Schaeverbeke T, Sibilia J. Bone and joint disease associated with primary immune deficiencies. Jt Bone Spine 2005;72:503–14.CrossRef
21.
Heeney MM, Zimmerman SA, Ware RE. Childhood autoimmune cytopenia secondary to unsuspected common variable immunodeficiency. Pediatrics 2003;143:662–5.CrossRef
22.
Knight AK, Cunningham-Rundles C. Inflammatory and autoimmune complications of common variable immune deficiency. Autoimmun Rev 2006;5:156–9.PubMedCrossRef
23.
Arkwright PD, Abinun M, Cant AJ. Autoimmunity in human primary immunodeficiency diseases. Blood 2002;99:2694–702.PubMedCrossRef
24.
Brandt D, Gershwin ME. Common variable immune deficiency and autoimmunity. Autoimmun Rev 2006;5:465–70.PubMedCrossRef
25.
Bacchelli C, Buckridge S, Thrasher AJ, Gaspar HB. Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency. Clin Exp Immunol 2007;149:401–9.PubMed
26.
Schäffer AA, Salzer U, Hammarström L, Grimbacher B. Deconstructing common variable immunodeficiency by genetic analysis. Curr Opin Genet Dev 2007;17:201–12.PubMedCrossRef
27.
Mullighan CG, Marshall SE, Welsh KI. Mannose binding lectin polymorphisms are associated with early age of disease onset and autoimmunity in common variable immunodeficiency. Scand J Immunol 2000;51:111–122.PubMedCrossRef
28.
Goldacker S, Warnatz K. Tackling the heterogeneity of CVID. Curr Opin Allergy Clin Immunol 2005;5:504–9.PubMedCrossRef
29.
Zhang L, Radigan L, Salzer U, Behrens TW, Grimbacher B, Diaz G, Bussel J, Cunningham-Rundles C. Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes. J Allergy Clin Immunol 2007;120:178–85.CrossRef
30.
Di Renzo M, Pasqui AL, Auteri A. Common variable immunodeficiency: a review. Clin Exp Med 2004;3:211–7.PubMedCrossRef
31.
Taubenheim N, von Hornung M, Durandy A, Warnatz K, Corcoran L, Peter HH, Eibel H. Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients. J Immunol 2005;175:5498–503.PubMed
32.
Brouet JC, Chedeville A, Fermand JP, Royer B. Study of the B cell memory compartment in common variable immunodeficiency. Eur J Immunol 2000;30:2516–20.PubMedCrossRef
33.
Jacquot S, Maçon-Lemaître L, Paris E, Kobata T, Tanaka Y, Morimoto C, Schlossman SF, Tron F. B cell co-receptors regulating T cell dependent antibody production in common variable immunodeficiency: CD27 pathway defects identify subsets of severely immunocompromised patients. Int Immunol 2001;13:871–6.PubMedCrossRef
34.
Warnatz K, Denz A, Dräger R, Braun M, Groth C, Wolff-Vorbeck G, Eibel H, Schlesier M, Peter HH. Severe deficiency of switched memory B cells (CD27+IgM−IgD−) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood 2002;99:1544–51.PubMedCrossRef
35.
Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L, Chevret S, Debré P, Schmitt C, Oksenhendler E. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol 2003;23:385–400.PubMedCrossRef
36.
Giovannetti A, Pierdominici M, Mazzetta F, Marziali M, Renzi C, Mileo AM, De Felice M, Mora B, Esposito A, Carello R, Pizzuti A, Paggi MG, Paganelli R, Malorni W, Aiuti F. Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. J Immunol 2007;178:3932–43.PubMed
37.
Vlková M, Thon V, Sárfyová M, Bláha L, Svobodník A, Lokaj J, Litzman J. Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin Exp Immunol 2006;143:373–9.PubMedCrossRef
38.
Eisenstein EM, Jaffe JS, Strober W. Reduced interleukin-2 (IL-2) production in common variable immunodeficiency is due to a primary abnormality of CD4+ T cell differentiation. J Clin Immunol 1993;13:247–58.PubMedCrossRef
39.
Holm AM, Aukrust P, Damas JK, Muller F, Halvorsen B, Froland S. Abnormal interleukin-7 function in common variable immunodeficiency. Blood. 2005;105:2887–2890.PubMedCrossRef
40.
De Vera MJ, Al-Harthi L, Gewurz AT. Assessing thymopoiesis in patients with common variable immunodeficiency as measured by T-cell receptor excision circles. Ann Allergy Asthma Immunol 2004;93:478–84.PubMedCrossRef
41.
Isgrò A, Marziali M, Mezzaroma I, Luzi G, Mazzone AM, Guazzi V, Andolfi G, Cassani B, Aiuti A, Aiuti F. Bone marrow clonogenic capability, cytokine production, and thymic output in patients with common variable immunodeficiency. J Immunol 2005;174:5074–81.PubMed
42.
Goldberg AC, Eliaschewitz FG, Montor WR, Baracho GV, Errante PR, Callero MA, Cardoso MRA, Braga PE, Kalil J, Sogayar MC, Rizzo LV. Exogenous leptin restores in vitro T cell proliferation and cytokine synthesis in patients with common variable immunodeficiency syndrome. Clin Immunol 2005;114:147–53.PubMedCrossRef
43.
Holm AM, Sivertsen EA, Tunheim SH, Haug T, Bjerkeli V, Yndestad A, Aukrust P, Frøland SS. Gene expression analysis of peripheral T cells in a subgroup of common variable immunodeficiency shows predominance of CCR7− effector-memory T cells. Clin Exp Immunol 2004;138:278–89.PubMedCrossRef
44.
Cunningham-Rundles C, Radigan L. Deficient IL-12 and dendritic cell function in common variable immune deficiency. Clin Immunol 2005;115:147–53.PubMedCrossRef
45.
Aspalter RM, Sewell WA, Dolman K, Farrant J, Webster AD. Deficiency in circulating natural killer (NK) cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia. Clin Exp Immunol 2000;121:506–14.PubMedCrossRef
46.
Amoras AL, Kanegane H, Miyawaki T, Vilela MM. Defective Fc−, CR1− and CR3− mediated monocyte phagocytosis and chemotaxis in common variable immunodeficiency and X-linked agammaglobulinemia patients. J Investig Allergol Clin Immunol 2003;13:181–8.PubMed
47.
Holm AM, Aukrust P, Aandahl EM, Muller F, Tasken K, Froland SS. Impaired secretion of IL-10 by T cells from patients with common variable immunodeficiency—involvement of protein kinase A type I. J Immunol 2003;170:5772–7.PubMed
48.
Petrovsky N. The paradoxical association between immunodeficiency and autoimmunity: comment on the article by Atkinson. Arthritis Rheum 1996;39:179–80.PubMedCrossRef
49.
Sneller MC, Strober W. Abnormalities of lymphokine gene expression in patients with common variable immunodeficiency. J Immunol 1990;144:3762–9.PubMed
50.
Rump JA, Jahreis A, Schlesier M, Drager R, Melchers I, Peter HH. Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency. Clin Exp Immunol 1992;89:204–10.PubMed
51.
North ME, Ivory K, Funauchi M, Webster AD, Lane AC, Farrant J. Intracellular cytokine production by human CD4+ and CD8+ T cells from normal and immunodeficient donors using directly conjugated anti-cytokine antibodies and three-colour flow cytometry. Clin Exp Immunol 1996;105:517–22.PubMedCrossRef
52.
Ko J, Radigan L, Cunningham-Rundles C. Immune competence and switched memory B cells in common variable immunodeficiency. Clin Immunol 2005;116:37–41.PubMedCrossRef
53.
Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoantibody production by early human B cell precursors. Science 2003;301:1374–7.PubMedCrossRef
54.
Levy Y, Gupta N, Le Deist F, Garcia C, Fischer A, Weill JC, Reynaud CA. Defect in IgV gene somatic hypermutation in common variable immunodeficiency syndrome. Proc Natl Acad Sci USA 1998;95:13135–40.PubMedCrossRef
55.
Meffre E, Schaefer A, Wardemann H, Wilson P, Davis E, Nussenzweig MC. Surrogate light chain expressing human peripheral B cells produce self-reactive antibodies. J Exp Med 2004;199:145–50.PubMedCrossRef
56.
Jiang H, Chess L. An integrated view of suppressor T cell subsets in immunoregulation. J Clin Invest 2004;114:1198–208.PubMed
57.
Chatila TA. Role of regulatory T cells in human diseases. J Allergy Clin Immunol 2005;116:949–59.PubMedCrossRef
58.
Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004;22:531–62.PubMedCrossRef
59.
Baecher-Allan C, Hafler DA. Human regulatory T cells and their role in autoimmune disease. Immunol Rev 2006;212:203–16.PubMedCrossRef
60.
Lopes-da-Silva S, Detková D, Urban S. CD4+CD25high T cells and autoimmunity in Common Variable Immunodeficiency. Presented at the XI Meeting of the European Society for Immunodeficiencies (ESID). Versailles 2004.
61.
Fevang B, Yndestad A, Sandberg WJ, Holm AM, Müller F, Aukrust P, Frøland SS. Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo. Clin Exp Immunol 2007;147:521–5.PubMed
62.
Malek TR, Bayer AL. Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 2004;4:665–74.PubMedCrossRef
63.
Scheffold A, Huhn J, Hofer T. Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-) two to tango. Eur J Immunol 2005;35:1336–41.PubMedCrossRef
64.
Zhang H, Chua KS, Guimond M, Kapoor V, Brown MV, Fleisher TA, Long LM, Bernstein D, Hill BJ, Douek DC, Berzofsky JA, Carter CS, Read EJ, Helman LJ, Mackall CL. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med 2005;11:1238–43.PubMedCrossRef
65.
Crispin JC, Martinez A, Alcocer-Varela J. Quantification of regulatory T cells in patients with systemic lupus erythematosus. J Autoimmunity. 2003;21:273–6.CrossRef
66.
Goleva E, Cardona ID, Ou LS, Leung DY. Factors that regulate naturally occurring T regulatory cell-mediated suppression. J Allergy Clin Immunol 2005;116:1094–100.PubMedCrossRef
67.
Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med. 1991;325:110–7.PubMed
68.
RJ Kilic SS. Anti-tumour necrosis factor-alpha treatment of juvenile idiopathic arthritis in a patient with common variable immunodeficiency. J Trop Pediatr 2005;51:194–5.CrossRef
69.
Nos P, Bastida G, Beltran B, Aguas M, Ponce J. Crohn’s disease in common variable immunodeficiency: treatment with antitumor necrosis factor alpha. Am J Gastroenterol 2006;101:2165–6.PubMedCrossRef
70.
Kanai T, Watanabe M. Clinical application of human CD4+ CD25+ regulatory T cells for the treatment of inflammatory bowel diseases. Expert Opin Biol Ther 2005;5:451–62.PubMedCrossRef
71.
Cunningham-Rundles C, Kazbay K, Hassett J, Zhou Z, Mayer L. Brief report: enhanced humoral immunity in common variable immunodeficiency after long-term treatment with polyethylene glycol-conjugated interleukin-2. N Engl J Med 1994;331:918–21.PubMedCrossRef
72.
Rump JA, Jahreis A, Schlesier M, Stecher S, Peter HH. A double-blind, placebo-controlled, crossover therapy study with natural human IL-2 (nhuIL-2) in combination with regular intravenous gammaglobulin (IVIG) infusions in 10 patients with common variable immunodeficiency (CVID). Clin Exp Immunol 1997;110:167–73.PubMed
73.
Spickett GP, Farrant J, North ME, Zhang J, Morgan L, Webster ADB. Common variable immunodeficiency: how many diseases? Immunol Today 1998;18:315–28.
74.
Bryant A, Calver NC, Toubi E, Webster AD, Farrant J. Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2. Clin Immunol Immunopathol 1990;56:239–48.PubMedCrossRef
75.
Alachkar H, Taubenheim N, Haeney MR, Durandy A, Arkwright PD. Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clin Immunol 2006;120:310–8.PubMedCrossRef
76.
Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 2008;111:77–85.PubMedCrossRef
Metadata
Title
Autoimmunity in Common Variable Immunodeficiency
Authors
Susana Lopes-da-Silva
Luiz Vicente Rizzo
Publication date
01-05-2008
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue Special Issue 1/2008
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-008-9172-9

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