Selective deficiency of immunoglobulin A (IgAD) and common variable immunodeficiency (CVID) are genetically closely related diseases, both of unknown pathogenesis. A plethora of abnormalities in lymphocyte subpopulations and expression of activation markers were repeatedly documented in CVID patients, while almost no data are available about lymphocyte subpopulations in IgAD patients. We determined basic lymphocyte subpopulations and those subpopulations that were reported to be abnormal in CVID patients (CD25, human leucocyte antigen (HLA)-DR CD45RA, CD45RO, CD27, CD28 and CD29 on both CD4(+) and CD8(+) cells, CD57 and CD38 on CD8(+) cells, CD21, CD27, IgM, IgD on B lymphocytes) in 85 patients with IgAD, 47 patients with CVID and in 65 healthy controls. Statistical analysis was performed by the Mann-Whitney U-test; significant P-values were determined by means of Bonferoni's correction. Our results showed an increase in the relative number of CD8(+) cells and a decrease in the absolute number of CD4(+) cells compared to healthy people, but similar abnormalities in CVID patients were much more expressed. IgAD patients had significantly decreased expression of HLA-DR and increased expression of CD25 on CD4(+) lymphocytes, also CD29 expression was decreased on CD8(+) cells, while other activation/differentiation markers on T cells (including the expression of CD45RA and CD45RO antigens) were not changed. There were no statistically significant abnormalities in B lymphocyte developmental stages in IgAD patients compared to healthy controls. Our observation showed that the majority of T and B lymphocyte subpopulation abnormalities described previously in CVID are not present in IgAD patients.

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

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Weber-Mzell D, Kotanko P, Hauer AC, et al. Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians. Eur J Clin Invest. 2004;34:224–8. PubMed

Hammarström L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID) Clin Exp Immunol. 2000;120:225–31. PubMed PMC

Vorechovsky I, Zetterquist H, Paganelli R, et al. Family and linkage study of selective IgA deficiency and common variable immunodeficiency. Clin Immunol Immunopathol. 1995;77:185–92. PubMed

Litzman J, Sevcikova I, Stikarovska D, Pikulova Z, Pazdirkova A, Lokaj J. IgA deficiency in Czech healthy individuals and selected patient groups. Int Arch Allergy Immunol. 2000;123:177–80. PubMed

Castigli E, Wilson SA, Garibyan L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37:829–34. PubMed

Salzer U, Chapel HM, Webster AD, et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37:820–8. PubMed

Espanol T, Catala M, Hernandez M, Caragol I, Bertran JM. Development of a common variable immunodeficiency in IgA-deficient patients. Clin Immunol Immunopathol. 1996;80:333–5. PubMed

Fischer MB, Hauber I, Eggenbauer H, et al. A defect in the early phase of T-cell receptor-mediated T-cell activation in patients with common variable immunodeficiency. Blood. 1994;84:4234–41. PubMed

Thon V, Wolf HM, Sasgary M, et al. Defective integration of activating signals derived from the T cell receptor (TCR) and costimulatory molecules in both CD4+ and CD8+ T lymphocytes of common variable immunodeficiency (CVID) patients. Clin Exp Immunol. 1997;10:174–81. PubMed PMC

Fischer MB, Wolf HM, Hauber I, et al. Activation via the antigen receptor is impaired in T cells, but not in B cells from patients with common variable immunodeficiency. Eur J Immunol. 1996;26:231–7. PubMed

Holm AM, Aukrust P, Aandahl EM, Muller F, Tasken K, Fröland 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

North ME, Webster AD, Farrant J. Primary defect in CD8+ lymphocytes in the antibody deficiency disease (common variable immunodeficiency): abnormalities in intracellular production of interferon-gamma (IFN-gamma) in CD28+ (‘cytotoxic’) and CD28-(‘suppressor’) CD8+ subsets. Clin Exp Immunol. 1998;111:70–5. PubMed PMC

Ferrer JM, Iglesias J, Hernandez M, Matamoros N. Alterations in interleukin secretion (IL-2 and IL-4) by CD4 and CD4 CD45RO cells from common variable immunodeficiency (CVI) patients. Clin Exp Immunol. 1995;102:286–9. PubMed PMC

Farrant J, Spickett G, Matamoros N, et al. Study of B and T cell phenotypes in blood from patients with common variable immunodeficiency (CVID) Immunodeficiency. 1994;5:159–69. PubMed

Lebranchu Y, Thibault G, Degenne D, Bardos P. Abnormalities in CD4+ T lymphocyte subsets in patients with common variable immunodeficiency. Clin Immunol Immunopathol. 1991;61:83–92. PubMed

Guazzi V, Aiuti F, Mezzaroma I, et al. Assessment of thymic output in common variable immunodeficiency patients by evaluation of T cell receptor excision circles. Clin Exp Immunol. 2002;129:346–53. PubMed PMC

Nordoy I, Müller F, Aukrust P, Froland SS. Adhesion molecules in common variable immunodeficiency (CVID) − a decrease in 1-selectin-positive T lymphocytes. Clin Exp Immunol. 1998;114:258–63. PubMed PMC

Baumert E, Wolff-Vorbeck G, Schlesier M, Peter HH. Immunophenotypical alterations in a subset of patients with common variable immunodeficiency (CVID) Clin Exp Immunol. 1992;90:25–30. PubMed PMC

Vlkova M, Thon V, Sarfyova M, et al. Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin Exp Immunol. 2006;143:373–9. PubMed PMC

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. PubMed

Agematsu K, Futatani T, Hokibara S, et al. Absence of memory B cells in patients with common variable immunodeficiency. Clin Immunol. 2002;103:34–42. 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;99:1544–51. PubMed

Ferry BL, Jones EA, Bateman EA, et al. Measurement of peripheral B cell subpopulations in common variable immunodeficiency (CVID) using a whole blood method. Clin Exp Immunol. 2005;140:532–9. PubMed PMC

Piqueras B, Lavenu-Bombled C, Galicier L, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. 2003;23:385–400. PubMed

Raziuddin S, Elawad ME, Benjamin B. T-cell abnormalities in antibody deficiency syndromes. Scand J Immunol. 1989;30:419–24. PubMed

Litzman J, Stouracova M, Krejci M, Thon V, Lokaj J. T-lymphocytes in IgA deficiency. Scripta Med Facult Med Univ Brunensis Masarykianae. 2001;74:345–52.

Melamed I, Zakuth V, Kark JO, Spirer Z. The immune system in isolated IgA deficiency. J Clin Lab Immunol. 1985;17:163–6. PubMed

Klemola TK, Eskola J, Savilahti E. T- and B-cell functions in IgA-deficient patients. Scand J Immunol. 1988;28:301–6. PubMed

Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Clin Immunol. 1999;93:190–7. PubMed

Winer BJ, Brown DR, Michels KM. 3. New York: McGraw-Hill; 1991. Statistical principles in experimental design.

Caruso AS, Licenziati M, Corulli AD, et al. Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation. Cytometry. 1997;27:71–6. PubMed

Asano T, Kaneko H, Terada T, et al. Molecular analysis of B-cell differentiation in selective or partial IgA deficiency. Clin Exp Immunol. 2004;136:284–90. PubMed PMC

Wang Z, Yunis D, Irigoyen M, et al. Discordance between IgA switching at the DNA level and IgA expression at the mRNA level in IgA-deficient patients. Clin Immunol. 1999;91:263–70. PubMed

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