INTRODUCTION: Previous studies showed that several lymphocyte abnormalities seen in the most frequent symptomatic immunoglobulin deficiency, common variable immunodeficiency (CVID), were also observed in a genetically related asymptomatic disorder - selective IgA deficiency (IgAD). In this study we searched for abnormalities in the differentiation stages of T cells as well as for similarities of these abnormalities in CVID and IgAD patients. MATERIAL AND METHODS: Using flow cytometry in 80 patients with IgAD, 48 patients with CVID, and 80 control persons we determined T-lymphocyte subsets: both CD4 and CD8 were divided into the naïve CD45RO-CD27+, early differentiated CD45RO+CD27+, late differentiated CD45RO+CD27- and fully differentiated effector CD45RO-CD27- memory T cells, as well as Treg cells, defined as CD4+CD25highCD127low T cells. RESULTS: An increase of CD4+ and CD8+ late differentiated memory cells was observed comparing CVID patients to controls, as well as comparing IgAD patients to controls. In CVID patients an increase of CD4+ early differentiated memory cells, a decrease of CD8+ intermediate memory cells, and CD4+ and CD8+ naïve cells were found as well. The abnormalities in IgAD patients might be explained by higher CMV seropositivity observed in our IgAD. We confirmed the repeatedly published decrease of Treg cells in CVID patients, while Treg cells in IgAD patients were increased compared to controls. CONCLUSIONS: Our results show T-cell activation not only in CVID, but also in IgAD patients. The increase in IgAD patients may be influenced by a more frequent CMV infection in our group of IgAD patients.

Department of Clinical Immunology and Allergology St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Institute of Biostatistics and Analyses Masaryk University Brno Czech Republic

Zobrazit více v PubMed

Latiff AH, Kerr MA. The clinical significance of immunoglobulin A deficiency. Ann Clin Biochem. 2007;44:131–139. PubMed

Cunningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol. 2001;21:303–309. PubMed

Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009;145:709–727. PubMed PMC

Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48. PubMed

Quinti I, Soresina A, Spadaro G, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27:308–316. PubMed

Abolhassani H, Amirkashani D, Parvaneh N, et al. Autoimmune phenotype in patients with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2013;23:323–329. PubMed

Hammarström L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID) Clin Exp Immunol. 2000;120:225–231. PubMed PMC

Rezaei N, Abolhassani H, Kasraian A, et al. Family study of pediatric patients with primary antibody deficiencies. Iran J Allergy Asthma Immunol. 2013;12:377–382. PubMed

Wright JJ, Wagner DK, Blaese RM, et al. Characterization of common variable immunodeficiency: identification of a subset of patients with distinctive immunophenotypic and clinical features. Blood. 1990;76:2046–2051. PubMed

Nechvatalova J, Pikulova Z, Stikarovska D, et al. B-lymphocyte Subpopulations in Patients with Selective IgA Deficiency. J Clin Immunol. 2012;32:441–448. PubMed

Vlková M, Thon V, Sárfyová M, et al. Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin Exp Immunol. 2006;143:373–379. PubMed PMC

Litzman J, Vlková M, Pikulová Z, et al. T and B lymphocyte subpopulations and activation/differentiation markers in patients with selective IgA deficiency. Clin Exp Immunol. 2007;147:249–254. PubMed PMC

Jaffe JS, Strober W, Sneller MC. Functional abnormalities of CD8+ T cells define a unique subset of patients with common variable immunodeficiency. Blood. 1993;82:192–201. PubMed

Melo KM, Carvalho KI, Bruno FR, et al. A decreased frequency of regulatory T cells in patients with common variable immunodeficiency. PLoS One. 2009;4:e16269. PubMed PMC

Mouillot G, Carmagnat M, Gérard L, et al. B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J Clin Immunol. 2010;30:746–755. PubMed

Arandi N, Mirshafiey A, Jeddi-Tehrani M, et al. Evaluation of CD4+CD25+FOXP3+ regulatory T cells function in patients with common variable immunodeficiency. Cell Immunol. 2013;281:129–133. PubMed

Aukrust P, Frøland SS, Müller F. Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features. Clin Exp Immunol. 1992;89:211–216. PubMed PMC

Litzman J, Nechvatalova J, Xu J, et al. Chronic immune activation in common variable immunodeficiency (CVID) is associated with elevated serum levels of soluble CD14 and CD25 but not endotoxaemia. Clin Exp Immunol. 2012;170:321–332. PubMed PMC

Young JL, Ramage JM, Gaston JS, Beverley PC. In vitro responses of human CD45R0brightRA- and CD45R0- RAbright T cell subsets and their relationship to memory and naive T cells. Eur J Immunol. 1997;27:2383–2390. PubMed

Hamann D, Baars PA, Rep MH, et al. Phenotypic and functional separation of memory and effector human CD8+ T cells. J Exp Med. 1997;186:1407–1418. PubMed PMC

Sallusto F, Lenig D, Förster R, et al. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401:708–712. PubMed

Maenetje P, Riou C, Casazza JP, et al. A steady state of CD4+ T cell memory maturation and activation is established during primary subtype C HIV-1 infection. J Immunol. 2010;184:4926–4935. PubMed

Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999;93:190–197. PubMed

Liu W, Putnam AL, Xu-Yu Z, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med. 2006;203:1701–1711. PubMed PMC

Thongpan M, Kitiyakara C, Louischaroen Y, et al. Analysis of Foxp3, CD25, and CD127 expressed on regulatory T cells in Thai subjects. Asian Pac J Allergy Immunol. 2009;27:137–145. PubMed

Horn J, Manguiat A, Berglund LJ, et al. Decrease in phenotypic regulatory T cells in subsets of patients with common variable immunodeficiency. Clin Exp Immunol. 2009;156:446–454. PubMed PMC

Libri V, Azevedo RI, Jackson SE, et al. Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4+CD45RA+CD27+ T cells: the potential involvement of interleukin-7 in this process. Immunology. 2011;132:326–339. PubMed PMC

Mackus WJ, Frakking FN, Grummels A, et al. Expansion of CMV-specific CD8+CD45RA+CD27- T cells in B-cell chronic lymphocytic leukemia. Blood. 2003;102:1057–1063. PubMed

Bateman EA, Ayers L, Sadler R, et al. T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections. Clin Exp Immunol. 2012;170:202–211. PubMed PMC

Giovannetti A, Pierdominici M, Mazzetta F, et al. Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. J Immunol. 2007;178:3932–3943. PubMed

Warnatz K, Denz A, Dräger R, et al. 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;99:1544–1551. PubMed

Burgers WA, Riou C, Mlotshwa M, et al. Association of HIV-specific and total CD8+ T memory phenotypes in subtype C HIV-1 infection with viral set point. J Immunol. 2009;182:4751–4761. PubMed PMC

Marashi SM, Raeiszadeh M, Enright V, et al. Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2012;129:1349–1356.e3. PubMed

Papagno L, Spina CA, Marchant A, et al. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol. 2004;2:E20. PubMed PMC

Shen CY, Chang WW, Chang SF, et al. Seroepidemiology of cytomegalovirus infection among children between the ages of 4 and 12 years in Taiwan. J Med Virol. 1992;37:72–75. PubMed

Mustakangas P, Sarna S, Ammälä P, et al. Human cytomegalovirus seroprevalence in three socioeconomically different urban areas during the first trimester: a population-based cohort study. Int J Epidemiol. 2000;29:587–591. PubMed

Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531–562. PubMed

Cools N, Ponsaerts P, Van Tendeloo VF, Berneman ZN. Regulatory T cells and human disease. Clin Dev Immunol. 2007;2007:89195. PubMed PMC

Soheili H, Abolhassani H, Arandi N, et al. Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities. Int Arch Allergy Immunol. 2013;160:208–214. PubMed

Freguja R, Gianesin K, Mosconi I, et al. Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children. Clin Exp Immunol. 2011;164:373–380. PubMed PMC

Punkosdy GA, Blain M, Glass DD, et al. Regulatory T-cell expansion during chronic viral infection is dependent on endogenous retroviral superantigens. Proc Natl Acad Sci U S A. 2011;108:3677–3682. PubMed PMC

Yu GP, Chiang D, Song SJ, et al. Regulatory T cell dysfunction in subjects with common variable immunodeficiency complicated by autoimmune disease. Clin Immunol. 2009;131:240–253. PubMed PMC