Common variable immunodeficiency in adults: Current diagnostic protocol and laboratory measures

Expert Review of Clinical Immunology

Volumn 9, Issue 10, 2013, Pages 959-977

  Kumar, Yashwant ^a   Bhatia, Alka ^a  

^a POSTGRADUATE INSTITUTE OF MEDICAL EDUCATION AND RESEARCH   (India)

Author keywords

class switched memory B cells; CVID; flow cytometry; hypogammaglobulinemia; immunoglobulins; memory B cells

Indexed keywords

ANTIBODY RESPONSE; CELL PROLIFERATION; CLINICAL FEATURE; COMMON VARIABLE IMMUNODEFICIENCY; DIAGNOSTIC APPROACH ROUTE; DIFFERENTIAL DIAGNOSIS; DISEASE COURSE; FLOW CYTOMETRY; IMMUNOGLOBULIN DEFICIENCY; LABORATORY TEST; MEMORY CELL; PATHOGENESIS; REVIEW;

ADULT; ANIMALS; CLINICAL LABORATORY TECHNIQUES; COMMON VARIABLE IMMUNODEFICIENCY; HUMANS;

EID: 84886937375     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1586/1744666X.2013.836967     Document Type: Review

References (134)

1. Cunningham-Rundles C, Maglione PJ. Common variable immunodeficiency. J. Allergy Clin. Immunol. 129(5), 1425-1426 e3 (2012).
2. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin. Immunol. 92, 34-48 (1999).
3. Salzer U, Warnatz K, Peter HH. Common variable immunodeficiency-an update. Arthritis Res. Ther. 14(5), 223 (2012).
4. Park MA, Li JT, Hagan JB et al. Common variable immunodeficiency: a new look at an old disease. Lancet 372, 489-502 (2008).
5. Cunningham-Rundles C. How I treat common variable immune deficiency. Blood 116, 7-15 (2010).
6. Cunningham-Rundles C. Clinical and immunologic analysis of 103 patients with common variable immunodeficiency. J. Clin. Immunol. 9, 22-33 (1989).
7. Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin. Exp. Immunol. 120, 225-231 (2000).
8. Castigli E, Geha RS. TACI, isotype switching, CVID and IgAD. Immunol. Res. 38, 102-111 (2007).
9. Bonilla FA, Bernstein IL, Khan DA et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann. Allergy Asthma Immunol. 94(5), S1-63 (2005).
10. Stray-Pedersen A, Abrahamsen TG, Frøland SS. Primary immunodeficiency diseases in Norway. J. Clin. Immunol. 20, 477-485 (2000).
11. Cunningham-Rundles C. The many faces of common variable immunodeficiency. Hematol. Am. Soc. Hematol Educ. Program 2012, 301-305 (2012)
12. IUIS. Primary immunodeficiency diseases. Report of an IUIS Scientific committee. International Union of Immunological Societies. Clan. Exp. Immune. 118, 1-28 (1999).
13. Kokron CM, Errante PR, Barros MT et al. Clinical and laboratory aspects of common variable immunodeficiency. An. Acad. Bras. Cienc. 76(4), 707-726 (2004).
14. Oksenhendler E, Gérard L, Fieschi C et al. DEFI Study Group: Infections in 252 patients with common variable immunodeficiency. Clin. Infect. Dis. 46, 1547-1554 (2008).
15. Yong PFK, Thaventhiran JED, Grimbacher B. "A rose is a rose is a rose, " but CVID is not CVID: common variable immune deficiency (CVID), what do we know in 2011? Adv. Immunol. 111, 47-107 (2011).
16. Schroeder HW, Schroeder HW, Sheikh SM. The complex genetics of common variable immunodeficiency. J. Investig. Med. 52, 90-103 (2004).
17. Vorechovsky I, Cullen M, Carrington M, Hammarstrom L, Webster AD. Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families. J. Immunol. 164, 4408-4416 (2000).
18. Oksenhendler E, Gérard L, Fieschi C et al. DEFI Study Group: Infections in 252 patients with common variable immunodeficiency. Clin. Infect. Dis. 46, 1547-1554 (2008).
19. Vorechovsky I, Webster ADB, Plebani A, Hammarstrom L. Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences and the role of anti-IgA antibodies in disease predisposition. Am. J. Hum. Genet. 64, 1096-1099 (1999).
20. Slyper AH, Pietryga D. Conversion of selective IgA deficiency to common variable immunodeficiency in an adolescent female with 18q deletion syndrome. Eur. J. Pediatr. 156, 155-156 (1997).
21. Aghamohammadi A, Moin M, Kouhi A et al. Chromosomal radiosensitivity in patients with common variable immunodeficiency. Immunobiol. 213(5), 447-454 (2008).
22. 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. Immun. 27, 308-316 (2007).
23. Chapel H, Lucas M, Lee M et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood 112, 277-286 (2008).
24. Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood 119, 1650-1657 (2012).
25. Durandy A, Honjo T. Human genetic defects in class-switch recombination (hyper-IgM syndromes). Curr. Opin. Immunol. 13(5), 543-548 (2001).
26. Whelan MA, Hwan WH, Beausoleil J, Hauck WW, McGeady SJ. Infants presenting with recurrent infections and low immunoglobulins: characteristics and analysis of normalization. J. Clin. Immunol. 26(1), 7-11 (2006).
27. Al-herz W, Bousfiha A, Casanova J et al. Primary Immunodeficiency Diseases: an update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Front Immunol. 2, 54 (2011).
28. Botto M, Kirschfink M, Macor P, Pickering MC, Würzner R, Tedesco F. Complement in human diseases: lessons from complement deficiencies. Mol Immunol. 46(14), 2774-2783 (2009).
29. Lekstrom-Himes JA, Allin JI. Immunodeficiency diseases caused by defects in phagocytes. N. Engl. J. Med. 343(23), 1703-1714 (2000).
30. Etzioni A, Doerschuk CM, Harlan JM. Of man and mouse: leukocyte and endothelial adhesion molecule deficiencies. Blood 94, 3281-3288 (1999).
31. Mohammadinejad P, Aghamohammadi A, Abolhassani H et al. Pediatric patients with common variable immunodeficiency: long-term follow-up. J. Investig Allergol Clin. Immunol. 22(3), 208-214 (2012).
32. Berron-Ruiz L, Lopez-Herrera G, Vargas-Hernandez A et al. Lymphocytes and B-cell abnormalities in patients with common variable immunodeficiency (CVID). Allergol.Immunopathol. (Madr). doi:10.1016/j.aller.2012.07.016 (2013) (Epub ahead of print).
33. Bayry J, Lacroix-Desmazes S, Kazatchkine MD et al. Common variable immunodeficiency is associated with defective functions of dendritic cells. Blood 104(8), 2441-2443 (2004).
34. Aspalter RM, Sewell WAC, Dolman K, Farrant J, Webster ABD. Deficiency in circulating natural killer (NK) cell subsets in common variable immunodeficiency and X-linked agammaglobulinemia. Clin. Exp. Immunol. 121, 506-514 (2000).
35. Fulcher DA, Avery DT, Fewings NL et al. Invariant natural killer (iNK) T cell deficiency in patients with common variable immunodeficiency. Clin. Exp. Immunol. 157(3), 365-369 (2009).
36. Carvalho KI, Melo KM, Bruno FR et al. Skewed distribution of circulating activated natural killer T (NKT) cells in patients with common variable immunodeficiency disorders (CVID). PLoS ONE 5(9), e12652 (2010).
37. 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. 170(2), 202-211 (2012).
38. Holm AM, Tjonnfjord G, Yndestad A et al. Polyclonal expansion of large granular lymphocytes in common variable immunodeficiency-association with neutropenia. Clin. Exp. Immunol. 144, 418-424 (2006).
39. Malphettes M, Gérard L, Carmagnat M et al. DEFI Study Group: late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect. Clin. Infect. Dis. 49, 1329-1338 (2009).
40. Rolink AG, Andersson J, Melchers F. Characterization of immature B cells by a novel monoclonal antibody, by turnover and by mitogen reactivity. Eur. J. Immunol. 28, 3738-3748 (1998).
41. Weller S, Braun MC, Tan BK et al. Human blood IgM "memory". B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood 104, 3647-3654 (2004).
42. Liu YJ, Banchereau J. Regulation of B-cell commitment to plasma cells or to memory B cells. Semin. Immunol. 9, 235-240 (1997).
43. Arpin C, Dechanet J, van Kooten C et al. Generation of memory B cells and plasma cells in vitro. Science 268, 720-722 (1995).
44. Shi Y, Agematsu K, Ochs HD, Sugane K. Functional analysis of human memory B-cell subpopulations: IgD+ CD27+ B cells are crucial in secondary immune response by producing high affinity IgM. Clin. Immunol. 108, 128-137 (2003).
45. Fevang B, Yndestad B, Sandberg WJ et al. Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo. Clin. Exp. Immunol. 147(3), 521-525 (2007).
46. Carter CR, Aravind G, Smalle NL et al. Do defective B cells contribute to reduced Treg cells and autoimmunity in patients with Common Variable Immunodeficiency? Immunol. Lett. 148(1), 39-40 (2012).
47. Warnatz K, Denz A, Drager 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 99, 1544-1551 (2002).
48. Suchanek O, Sadler R, Bateman EA, Patel SY, Ferry BL. Immunophenotyping of putative human B1 B cells in healthy controls and common variable immunodeficiency (CVID) patients. Clin. Exp. Immunol. 170(3), 333-341 (2012).
49. Ochtrop ML, Goldacker S, May AM et al. T-and B-lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency. Blood 118, 309-318 (2011).
50. Taubenheim N, von Hornung M, Durandy A et al. Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients. J. Immunol. 175, 5498-5503 (2005).
51. Aghamohammadi A, Farhoudi A, Moin M et al. Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency. Clin. Diag. Lab. Immun. 7, 825-832 (2005).
52. Orange JS, Glessner JT, Resnick E et al. Genome-wide association identifies diverse causes of common variable immunodeficiency. J. Allergy Clin. Immunol. 127, 1360-1367 e1366 (2011).
53. Keller MD, Jyonouchi S. Chipping away at a mountain: genomic studies in common variable immunodeficiency. Autoimmun. Rev. 12(6), 687-689 (2013).
54. Amanzadeh A, Amirzargar AA, Mohseni N et al. Association of HLA-DRB1, DQA1 and DQB1 alleles and haplotypes with common variable immunodeficiency in Iranian patients. Avicenna. J. Med. Biotechnol. 4(2), 103-112 (2012).
55. Chapel H, Cunningham-Rundles C. Update in understanding Common Variable Immunodeficiency Disorders (CVIDs) and the management of patients with these conditions. Br. J. Haematol. 145(6), 709-727 (2009).
56. Mullighan CG, Fanning GC, Chapel HM, Welsh KI. TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease. J. Immunol. 159, 6236-6241 (1997).
57. 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. 51, 111-122 (2000).
58. Martinez-Pomar NRS, Ferrer J, Pons J et al. Elevated serum interleukin (IL)-12p40 levels in common variable immunodeficiency disease and decreased peripheral blood dendritic cells: analysis of IL-12p40 and interferon-gamma gene. Clin. Exp. Immunol. 144, 233-238 (2006).
59. Spyridakou C, Berry S, Phillipps J. Common variable immunodeficiency syndrome: a difficult diagnostic problem. J. Laryngol. Otol. 121, 1204-1206 (2007).
60. Conley M, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin. Immunol. 93, 190-197 (1999).
61. De Santis W, Esposito A, Conti V et al. Health care and infective aspects in patients affected by common variable immunodeficiency assisted in the Lazio Regional Authority Reference Centre for Primary Immunodeficiencies. Infez. Med. 14(1), 13-23 (2006).
62. Ameratunga R, Woon S, Gillis D, Koopmans W, Steele R New diagnostic criteria for Common Variable Immune Deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous Immunoglobulin. Clin. Exp. Immunol. doi:10.1111/cei.12178 (2013) (Epub ahead of print)
63. Durandy A, Revy P, Fischer A. Ochs H, Smith CIE, Puck JM. Autosomal hyper IgM syndromes caused by an intrinsic B cell defect. In: Primary Immunodeficiency Diseases-A Molecular and Genetic Approach (2nd Edition). Oxford University Press, New York, NY, 269-278 (2007).
64. Miles J, Riches P. The determination of IgG subclass concentration in serum by enzyme linked immunosorbent assay: establishment of age related reference ranges for cord blood samples, children aged 5-13 years and adults. Ann. Clin. Biochem. 31, 245-248 (1994).
65. Hare ND, Smith BJ, Ballas ZK. Antibody response to pneumococcal vaccination as a function of preimmunization titer. J. Allergy Clin. Immunol. 123(1), 195-200 (2009).
66. Cavaliere FM, Milito C, Martini H et al Quantification of IgM and IgA anti-pneumococcal capsular polysaccharides by a new ELISA assay: a valuable diagnostic and prognostic tool for common variable immunodeficiency. J. Clin. Immunol. 33(4), 838-846 (2013).
67. Rezaei N, Aghamohammadi A, Nourizadeh M et al. Cytokine Production by activated T Cells in common variable immunodeficiency. J. Investig. Allergol. Clin. Immunol. 20(3), 244-251 (2010).
68. Quah BJC, Parish CR. The use of Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) to Monitor Lymphocyte Proliferation.J. Vis. Exp. 44, e2259 (2010).
69. Jaffe JS, Eisenstein E, Sneller MC, Strober W. T-cell abnormalities in common variable immunodeficiency. Pediatr. Res. 33(1), S24-27 (1993).
70. Warnatz K, Schlesier M. Flowcytometric phenotyping of common variable immunodeficiency. Cytometry B. Clin. Cytom. 74(5), 261-271 (2008).
71. Ferry BL, Jones J, Bateman EA et al. Measurement of peripheral B cell sub populations in common variable immunodeficiency (CVID) using a whole blood method. Clin. Exp. Immunol. 140(3), 532-539 (2005).
72. Warnatz K, Denz A, Drager R et al. Severe deficiency of switched memory B cells (CD27(1)IgM(2) IgD(2)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood 99, 1544-1551 (2002).
73. 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 23, 385-400 (2003).
74. Wehr C, Kivioja T, Schmitt C et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 111, 77-85 (2008).
75. Webster ADB. Clinical and immunological spectrum of Common Variable Immunodeficiency (CVID). Iran. J. Allergy Asthma Immunol. 3(3), 103-113 (2004).
76. Giovannetti A, Pierdominici M, Mazzetta F et al. Unraveling the complexity of T cell abnormalities in common variable immunodeficiency. J. Immunol. 178, 3932-3943 (2007).
77. Fevang B, Yndestad A, Sandberg WJ et al. Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo. Clin. Exp. Immunol. 147, 521-525 (2007).
78. Carter CR, Arvind G, Smalle NL et al. Do defective B cells contribute to reduced Treg cells and autoimmunity in patients with common variable immunodeficiency? Immunol. Lett. 148, 39-40 (2012).
79. Salzer U, Bacchelli C, Buckridge S et al. Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes. Blood 113(9), 1967-1976 (2009).
80. Maarschalk-Ellerbroek LJ, Hoepelman AIM, van-Montfrans JM, Ellerbroek PM. The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital. J. Clin. Immunol. 32, 907-921 (2012).
81. Salzer U, Grimbacher B. Common variable immunodeficiency: the power of co-stimulation. Sem. Immunol. 18, 337-346 (2006).
82. Ramírez-Vargas N, Arablin-Oropeza SE, Mojica-Martínez D et al. Clinical and immunological features of common variable immunodeficiency in Mexican patients. Allergol. Immunopathol. (Madr). doi:10.1016/j.aller.2013.01. 007 (2013) (Epub ahead of print).
83. Abolhassani H, Aghamohammadi A, Abolhassani F, Eftekhar H, Heidarnia M, Rezaei N. Health policy for common variable immunodeficiency: burden of the disease. J. Investig. Allergol. Clin. Immunol. 21(6), 454-458 (2011).
84. Kainulainen L, Nikoskelainen J, Ruuskanen O. Diagnostic findings in 95 finnish patients with common variable immunodeficiency. J. Clin. Immun. 21, 145-149 (2001).
85. Yong PF, Workman S, Wahid F, Exley A, Webster AD, Ibrahim MA. Selective deficits in blood dendritic cell subsets in common variable immunodeficiency and X-linked agammaglobulinemia but not specific polysaccharide antibody deficiency. Clin. Immunol. 127(1), 34-42 (2008).
86. Viallard JF, Camou F, André M et al. Altered dendritic cell distribution in patients with common variable immunodeficiency. Arthritis. Res. Ther. 7(5), R1052-1055 (2005).
87. Scott-Taylor TH, Green MR, Eren E, Webster AD. Monocyte derived dendritic cell responses in common variable immunodeficiency. Clin. Exp. Immunol. 138(3), 484-490 (2004).
88. Cunningham-Rundles C, Radigan L. Deficient IL-12 and dendritic cell function in common variable immune deficiency. Clin. Immunol. 115(2), 147-153 (2005).
89. Cunningham-Rundles C, Radigan L, Knight AK, Zhang L, Bauer L, Nakazawa A. TLR9 activation is defective in common variable immune deficiency. J. Immunol. 176(3), 1978-1987 (2006).
90. Yu JE, Knight AK, Radigan L et al. Toll-like receptor 7 and 9 defects in common variable immunodeficiency. J. Allergy. Clin. Immunol. 124, 349-356 (2009).
91. Yu JE, Zhang L, Radigan L, Sanchez-Ramon S, Cunningham-Rundles C. TLR-mediated B cell defects and IFN-alpha in common variable immunodeficiency. J. Clin. Immunol. 32, 50-60 (2012).
92. Trujillo CM, Muskus C, Arango J, Patino PJ, Montoya CJ. Quantitative and functional evaluation of innate immune responses in patients with common variable immunodeficiency. J. Investig. Allergol. Clin. Immunol. 21(3), 207-215 (2011).
93. Giovannetti A, Pierdominici M, Mazzetta F et al. Unraveling the complexity of T cell abnormalities in common variable immunodeficiency. J. Immunol. 178, 3932-3943 (2007).
94. 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. 93, 478-484 (2004).
95. Arumugakani G, Wood PM, Carter CR. Frequency of Treg cells is reduced in CVID patients with autoimmunity and splenomegaly and is associated with expanded CD21lo B lymphocytes. J. Clin. Immunol. 30, 292-300 (2010).
96. 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. 156, 446-454 (2009).
97. Melo KM, Carvalho KI, Bruno FR et al. A decreased frequency of regulatory T cells in patients with common variable immunodeficiency. PLoS ONE 4, e6269 (2009).
98. Arandi N, Mirshafiey A, Abolhassani H et al. Frequency and expression of inhibitory markers of CD4(+) CD25(+) FOXP3(+) regulatory T Cells in patients with common variable immunodeficiency. Scand. J. Immunol. 77(5), 405-412 (2013).
99. Carter CR, Aravind G, Smalle NL, Cole JY, Savic S, Wood PM. CVID patients with autoimmunity have elevated T cell expression of granzyme B and HLA-DR and reduced levels of Treg cells. J. Clin. Pathol. 66(2), 146-150 (2013).
100. Holm AM, Sivertsen EA, Tunheim SH et al. 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. 138, 278-289 (2004).
101. Aukrust P, Lien E, Kristoffersen AK et al. Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency-possible immunologic and clinical consequences. Blood 87, 674-681 (1996).
102. Aukrust P, Svardal AM, Müller F, Lunden B, Berge RK, Frøland SS. Decreased levels of total and reduced glutathione in CD4C lymphocytes in common variable immunodeficiency are associated with activation of the tumor necrosis factor system: possible immunopathogenic role of oxidative stress. Blood 86, 1383-1391 (1995).
103. 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 84(12), 4234-4241 (1994).
104. Farrington M, Grosmaire LS, Nonoyama S et al. CD40 ligand expression is defective in a subset of patients with common variable immunodeficiency. Proc. Natl Acad. Sci. USA 91, 1099-1103 (1994).
105. Pozzi N, Gaetaniello L, Martire B et al. Defective surface expression of attractin on T cells in patients with common variable immunodeficiency (CVID). Clin. Exp. Immunol. 123, 99-104 (2001).
106. Bayry J, Hermine O, Webster DA, Lévy Y, Kaveri SV. Common variable immunodeficiency: the immune system in chaos. Trends Mol. Med. 11(8), 370-376 (2005).
107. Di RM, Serrano D, Zhou Z, George I, Becker K, Cunningham-Rundles C. Enhanced T cell apoptosis in common variable immunodeficiency: negative role of the fas/fas ligand system and of the Bcl-2 family proteins and possible role of TNF-RS. Clin. Exp. Immunol. 125(1), 117-122 (2001).
108. Agematsu K, Futatani T, Hokibara S et al. Absence of memory B cells in patients with common variable immunodeficiency. Clin. Immunol. 103, 34-42 (2002).
109. Bonhomme D, Hammarstrom L, Webster D et al. Impaired antibody affinity maturation process characterizes a subset of patients with common variable immunodeficiency. J. Immunol. 165, 4725-4730 (2000).
110. Andersen P, Permin H, Andersen V et al. Deficiency of somatic hypermutation of the antibody light chain is associated with increased frequency of severe respiratory tract infection in common variable immunodeficiency. Blood 105, 511-517 (2005).
111. Taubenheim N, von Hornung M, Durandy A et al. Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients. J. Immunol. 175, 5498-5503 (2005).
112. Denz A, Eibel H, Illges H, Kienzle G, Schlesier M, Peter HH. Impaired up-regulation of CD86 in B cells of "type A" common variable immunodeficiency patients. Eur. J. Immunol. 30, 1069-1077 (2000).
113. Groth C, Drager R, Warnatz K et al. Impaired up regulation of CD70 and CD86 in naive (CD27-) B cells from patients with common variable immunodeficiency (CVID). Clin. Exp. Immunol. 129, 133-139 (2002).
114. Foerster C, Voelxen N, Rakhmanov M et al. B cell receptor-mediated calcium signaling is impaired in B lymphocytes of type Ia patients with common variable immunodeficiency. J. Immunol. 184, 7305-7313 (2010).
115. Grimbacher B, Hutloff A, Schlesier M et al. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat. Immunol. 4, 261-268 (2003).
116. Takahashi N, Matsumoto K, Saito H et al. Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. J. Immunol. 182, 5515-5527 (2009).
117. Martinez-Pomar N, Detkova D, Arostegui JI et al. Role of TNFRSF13B variants in patients with common variable immunodeficiency. Blood 114, 2846-2848 (2009).
118. Salzer U, Chapel HM, Webster AD et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat. Genet. 37, 820-828 (2005).
119. Warnatz K, Salzer U, Rizzi M et al. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc. Natl Acad. Sci. USA 106, 13945-13950 (2009).
120. van Zelm MC, Reisli I, van der Burg M et al. An antibody-deficiency syndrome due to mutations in the CD19 gene. N. Engl. J. Med. 354, 1901-1912 (2006).
121. Vince N, Boutboul D, Mouillot G et al. Defects in the CD19 complex predispose to glomerulonephritis, as well as IgG1 subclass deficiency. J. Allergy Clin. Immunol. 127, 538-541 (2011).
122. Kuijpers TW, Bende RJ, Baars PA et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J. Clin. Invest. 120, 214-222 (2010).
123. Thiel J, Kimmig L, Salzer U et al. Genetic CD21 deficiency is associated with hypogammaglobulinemia. J. Allergy Clin. Immunol. 129, 801-810 (2012).
124. Frank MM, Durham NC. CD21 deficiency, complement, and the development of common variable immunodeficiency. J. Allergy Clin. Immunol. 129, 811-813 (2012).
125. van Zelm MC, Smet J, Adams B et al. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J. Clin. Invest. 120, 1265-1274 (2010).
126. Lopez-Herrera G, Tampella G, Pan-Hammarström Q et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am. J. Hum. Genet. 90, 986-1001 (2012).
127. Sekine H, Ferreira RC, Pan-Hammarström Q et al. Role for Msh5 in the regulation of Ig class switch recombination. Proc. Natl Acad. Sci. USA 104, 7193-7198 (2007).
128. Deane S, Selmi C, Naguwa SM, Teuber SS, Gershwin ME. Common variable immunodeficiency: etiological and treatment issues. Int. Arch. Allergy Immunol. 150, 311-324 (2009).
129. Bonilla FA, Bernstein IL, Khan DA et al Practice parameter for the diagnosis and management of primary immunodeficiency. Ann. Allergy Asthma Immunol. 94, S1-63 (2005).
130. Yong PF, Tarzi M, Chua I, Grimbacher B, Chee R. Common variable immunodeficiency: an update on etiology and management. Immunol. Allergy Clin. North Am. 28(2), 367-386 (2008).
131. Abolhassani H, Sagvand BT, Shokuhfar T, Mirminachi B, Rezaei N, Aghamohammadi A. A review on guidelines for management and treatment of common variable immunodeficiency. Expert Rev. Clin. Immunol. 9(6), 561-575 (2013).
132. Bisset LR, Lung TL, Kaelin M, Ludwig E, Dubs RW. Reference values for peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland. Eur. J. Haematol. 72(3), 203-212 (2004).
133. Chang WJ, Tan GB, Kuperan P. Establishment of adult peripheral blood lymphocyte subset reference range for an Asian population by single-platform flow cytometry: influence of age, sex, and race and comparison with other published studies. Clin. Diagn. Lab. Immunol. 11(1), 168-173 (2004).
134. Warnatz K, Schlesier M. Diagnostics for Common Variable Immunodeficiency Syndrome. In: Cellular Diagnostics. Basics, Methods and Clinical Applications of Flow Cytometry. Karger, Basel, 540-557 (2009).