The Complex Genetics of Common Variable Immunodeficiency

Journal of Investigative Medicine

Volumn 52, Issue 2, 2004, Pages 90-103

  Schroeder Jr , Harry W ^a,b,c,d   Schroeder III, Harry W ^a   Sheikh, Sofia M ^a  

^a The University of Alabama at Birmingham   (United States)

^b University of Alabama at Birmingham   (United States)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^d UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

Agammaglobulinemia; Common variable immunodeficiency; Immunoglobulin A deficiency; Major histocompatibility complex; Primary immunodeficiency

Indexed keywords

ANTIBIOTIC AGENT; ANTIMALARIAL AGENT; CAPTOPRIL; CARBAMAZEPINE; FENCLOFENAC; GLUCOCORTICOID; GOLD SALT; IMMUNOGLOBULIN; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 3; METRONIDAZOLE; PENICILLAMINE; PHENYTOIN; SALAZOSULFAPYRIDINE;

AGAMMAGLOBULINEMIA; CHROMOSOME 6; CLINICAL FEATURE; COMMON VARIABLE IMMUNODEFICIENCY; DIFFERENTIAL DIAGNOSIS; DISEASE PREDISPOSITION; FAMILIAL DISEASE; GENE LOCUS; GENETIC RISK; GENETIC SUSCEPTIBILITY; GIARDIASIS; HIGH RISK PATIENT; HUMAN; IMMUNE DEFICIENCY; IMMUNOGLOBULIN A DEFICIENCY; IMMUNOGLOBULIN BLOOD LEVEL; INFECTION; INHERITANCE; MAJOR HISTOCOMPATIBILITY COMPLEX; MEDICAL GENETICS; PATIENT MONITORING; PHENOTYPE; REVIEW; RISK FACTOR;

EID: 1642401333     PISSN: 17088267     EISSN: None     Source Type: Journal    
DOI: 10.1136/jim-52-02-17     Document Type: Review

References (116)

1. Rosen FS, Wedgwood RJ, Eibl MM, et al. Primary immunodeficiency diseases: report of a WHO Scientific Group. Clin Exp Immunol 1997;109 Suppl:1-28.
2. Flori NM, Llambi JM, Boren TE, et al. Primary immunodeficiency syndrome in Spain: first report of the National Registry in Children and Adults. J Clin Immunol 1997;17:333-9.
3. Oxelius VA, Laurell AB, Lindquist B, et al. IgG subclasses in selective IgA deficiency: importance of IgG2-IgA deficiency. N Engl J Med 1981;304:1476-7.
4. French MA, Denis KA, Dawkins R, Peter JB. Severity of infections in IgA deficiency: correlation with decreased serum antibodies to pneumococcal polysaccharides and decreased serum IgG2 and/or IgG4. Clin Exp Immunol 1995;100:47-53.
5. Rosen FS, Wedgwood RJ, Eibl MM, et al. Primary immunodeficiency diseases. Report of a WHO Scientific Group. Immunodefic Rev 1992;3:195-236.
6. Vyas GN, Perkins HA, Yang YM, Basantani GK. Healthy blood donors with selective absence of immunoglobulin A: prevention of anaphylactic transfusion reactions caused by antibodies to IgA. J Lab Clin Med 1975;85:838-42.
7. Burgio GR, Duse M, Monafo V, et al. Selective IgA deficiency: clinical and immunological evaluation of 50 pediatric patients. Eur J Pediatr 1980;133:101-6.
8. Johnson ML, Keeton LG, Zhu Z-B, et al. Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID). Clin Exp Immunol 1997;108:477-83.
9. Cooper MD, Lawton AR. Circulating B-cells in patients with immunodeficiency. Am J Pathol 1972;69:513-28.
10. Jacquot S, Macon-Lemaitre L, Paris E, et al. B cell co-receptors regulating T cell-dependent antibody production in common variable immunodeficiency: CD27 pathway defects identify subsets of severely immuno-compromised patients. Int Immunol 2001;13:871-6.
11. 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 2002;99:1544-51.
12. 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.
13. Grimbacher B, Hutloff A, Schlesier M, et al. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol 2003;4:261-8.
14. Spickett GP, Farrant J, North ME, et al. Common variable immunodeficiency: how many diseases?. Immunol Today 1997;18:325-8.
15. Hobbs JR. Immune imbalance in dysgammaglobulinaemia type IV. Lancet 1968;i:110-4.
16. Johansson SG, Hogman CF, Killander J. Quantitative immunoglobulin determination. Comparison of two methods. Estimation of normal levels and levels in persons lacking IgA and IgD. Acta Pathol Microbiol Scand 1968;74:519-30.
17. Bachman R. Studies on the serum gamma A-globulin level. III. The frequency of a-gamma A-globulinemia. Scand J Clin Lab Invest 1965;17:316-20.
18. Pereira LF, Sapina AM, Arroyo J, et al. Prevalence of selective IgA deficiency in Spain: more than we thought [letter]. Blood 1997;90:893.
19. Buckley RH. Clinical and immunologic features of selective IgA deficiency. Birth Defects Orig Art Ser 1975;11:134-42.
20. Lawton AR, Royal SA, Self KS, Cooper MD. IgA determinants on B lymphocytes in patients with deficiency of circulating IgA. J Lab Clin Med 1972;80:26-33.
21. Kanoh T, Mizumoto T, Yasuda N, et al. Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis. Vox Sang 1986;50:81-6.
22. Yadav M, Iyngkaran N. Low incidence of selective IgA deficiency in normal Malaysians. Med J Malaysia 1979;34:145-8.
23. Fasth A. Primary immunodeficiency disorders in Sweden: cases among children, 1974-1979. J Clin Immunol 1982; 2:86-92.
24. McCluskey DR, Boyd NAM. Prevalence of primary hypogammaglobulinemia in Northern Ireland. Proc R Coll Phys Edinb 1989;19:191-4.
25. Wollheim FA, Williams RC Jr. Immunoglobulin studies in six kindreds of patients with adult hypogammaglobulinemia. J Lab Clin Med 1965;66:433-45.
26. Volanakis JE, Zhu Z-B, Schaffer FM, et al. Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency. J Clin Invest 1992;89:1914-22.
27. Cunningham Rundles C. Genetic aspects of immunoglobulin A deficiency. Adv Hum Genet 1990;19:235-66.
28. Oen K, Petty RE, Schroeder ML. Immunoglobulin A deficiency: genetic studies. Tissue Antigens 1982;19:174-82.
29. Grundbacher FJ. Genetic aspects of selective immunoglobulin A deficiency. J Med Genet 1972;9:344-7.
30. Schaffer FM, Palermos J, Zhu Z-B, et al. Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes. Proc Natl Acad Sci U S A 1989;86:8015-9.
31. Ammann AJ, Hong R. Selective IgA deficiency: presentation of 30 cases and a review of the literature. Medicine 1971;50:223-36.
32. Schaffer FM, Monteiro RC, Volanakis JE, Cooper MD. IgA deficiency. Immunodefic Rev 1991;3:15-44.
33. Morell A, Muehlheim E, Schaad U, et al. Susceptibility to infections in children with selective IgA- and IgA-IgG subclass deficiency. Eur J Pediatr 1986;145:199-203.
34. West CD, Hong R, Holland NH. Immunoglobulin levels from the newborn period to adulthood and in immunoglobulin deficiency states. J Clin Invest 1962;41:2054-64.
35. Klemola T. Deficiency of immunoglobulin A. Ann Clin Res 1987;19:248-57.
36. Ostergaard PA. Clinical and immunological features of transient IgA deficiency in children. Clin Exp Immunol 1980;40:561-5.
37. Burks AW Jr, Steele RW. Selective IgA deficiency. Ann Allergy 1986;57:3-13.
38. Hanson LA, Soderstrom T, Oxelius VA. Immunoglobulin subclass deficiencies. Basel (Switzerland): Karger; 1986.
39. South MA, Wolheim FA, Warwick WJ, et al. Local deficiency of immune globulin A in the saliva of patients with chronic sinopulmonary disease. J Pediatr 1965;67:941-2.
40. Preud'homme JL, Hanson LA. IgG subclass deficiency. Immunodefic Rev 1990;2:129-49.
41. Aucouturier P, Lacombe C, Bremard C, et al. Serum IgG subclass levels in patients with primary immunodeficiency syndromes or abnormal susceptibility to infections. Clin Immunol Immunopathol 1989;51:22-37.
42. Amin N. Giardiasis: a common cause of diarrheal disease. Postgrad Med 1979;66:151-6, 158.
43. Watts WJ, Watts MB, Dai W, et al. Respiratory dysfunction in patients with common variable hypogammaglobulinemia. Am Rev Respir Dis 1986;134:699-703.
44. Sneller MC, Strober W, Eisenstein E, et al. New insights into common variable immunodeficiency. Ann Intern Med 1993;118:720-30.
45. Wagner DK, Wright JJ, Ansher AF, Gill VJ. Dysgonic fermenter 3-associated gastrointestinal disease in a patient with common variable hypogammaglobulinemia. Am J Med 1988;84:315-8.
46. Asherson GL. Late-onset hypogammaglobulinemia. In: Asherson GL, Webster AD, editors. Diagnosis and treatment of immunodeficiency. London: Blackwell Scientific Publications; 1980. p. 37-60.
47. Solley GO, Dickson ER, Gleich GJ, Stobo JD. Chronic active liver disease with common variable hypogammaglobulinemia. Mayo Clin Proc 1979;54:127-30.
48. Tong MJ, Nies KM, Redeker AG. Rapid progression of chronic active type B hepatitis in a patient with hypogammaglobulinemia. Gastroenterology 1977;73:1418-21.
49. Bjorkander J, Cunningham Rundles C, Lundin P, et al. Intravenous immunoglobulin prophylaxis causing liver damage in 16 of 77 patients with hypogammaglobulinemia or IgG subclass deficiency. Am J Med 1988;84:107-11.
50. Hermans PE, Diax-Buxo JA, Stobo JD. Idiopathic late-onset immunoglobulin deficiency. Am J Med 1976;61:221-36.
51. Loria RC, Jadidi S, Wedner HJ. Anaphylactic reaction to ampicillin in a patient with common variable immunodeficiency syndrome desensitized to penicillin. Ann Allergy 1987;59:15-6, 348.
52. Sander CA, Medeiros LJ, Weiss LM, et al. Lymphoproliferative lesions in patients with common variable immunodeficiency. Am J Surg Pathol 1992;16:1170-82.
53. Gatti RA, Good RA. Occurrence of malignancy in immunodeficiency diseases. Cancer 1971;28:89-98.
54. Kinlen LJ, Webster ADB, Bird AG, et al. Prospective study of cancer in patients with hypogammaglobulinemia. Lancet 1985;i:263-6.
55. Cunningham Rundles C, Siegal FP, Cunningham Rundles S, Lieberman P. Incidence of cancer in 98 patients with common variable immunodeficiency. J Clin Immunol 1987; 7:294-9.
56. Gonzalez Vitale JC, Gomez LG, Goldblum RM, et al. Immunoblastic lymphoma of small intestine complicating late-onset immunodeficiency. Cancer 1982;49:445-9.
57. Filipovich AH, Mathur A, Kamat D, et al. Lymphoproliferative disorders and other tumors complicating immunodeficiencies. Immunodeficiency 1994;5:91-112.
58. Mellemkjaer L, Hammarstrom L, Andersen V, et al. Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study. Clin Exp Immunol 2002;130:495-500.
59. Cunningham Rundles C, Lieberman P, Hellman G, Chaganti RSK. Non-Hodgkin lymphoma in common variable immunodeficiency. Am J Hematol 1991;37:69-74.
60. De Smet AA, Tubergen DG, Martel W. Nodular lymphoid hyperplasia of the colon associated with dysgammaglobulinemia. AJR Am J Roentgenol 1976;127:515-7.
61. Hermans PE, Huizenga KA, Hoffman HN, et al. Dysgammaglobulinemia associated with nodular lymphoid hyperplasia of the small intestine. Am J Med 1966;40:78-89.
62. Delamarre J, Dupas JL, Chivrac D, et al. Hypogammaglobulinemia with lymphoid nodular hyperplasia of the small bowel: endoscopic diagnosis of one case. Endoscopy 1976;8:214-6.
63. Bastlein C, Burlefinger R, Holzberg E, et al. Common variable immunodeficiency syndrome and nodular lymphoid hyperplasia in the small intestine. Endoscopy 1988;20:272-5.
64. Ranchod M, Lewin KJ, Dorfman RF. Lymphoid hyperplasia of the gastrointestinal tract. A study of 26 cases and review of the literature. Am J Surg Pathol 1978;2:383-400.
65. Shackleford MD, McAlister WH. Primary immunodeficiency diseases and malignancy. AJR Am J Roentgenol 1975; 123:144-53.
66. Hammarstrom L, Carlsson B, Smith CI, et al. Detection of IgA heavy chain constant region genes in IgA deficient donors: evidence against gene deletions. Clin Exp Immunol 1985; 60:661-4.
67. Hammarstrom L, de Lange GG, Smith CI. IgA2 allotypes determined by restriction fragment length polymorphism in IgA deficiency. Re-expression of the silent A2m(2) allotype in the children of IgA-deficient patients. J Immunogenet 1987;14:197-201.
68. Conley ME, Cooper MD. Immature IgA B cells in IgA-deficient patients. N Engl J Med 1981;305:495-7.
69. Islam KB, Baskin B, Nilsson L, et al. Molecular analysis of IgA deficiency: evidence for impaired switching to IgA. J Immunol 1994;152:1442-52.
70. Preud'homme JL, Griscelli C, Seligmann M. Immunoglobulins on the surface of lymphocytes in fifty patients with primary immunodeficiency diseases. Clin Immunol Immunopathol 1973;1:241-56.
71. Farrant J, Bryant A, Almandoz F, et al. B cell function in acquired "common-variable" hypogammaglobulinemia: proliferative responses to lymphokines. Clin Immunol Immunopathol 1989;51:196-204.
72. Cooper MD, Lawton AR, Bockman DE. Agammaglobulinemia with B lymphocytes. Specific defect of plasma-cell differentiation. Lancet 1971;ii:791-5.
73. Saxon A, Sidell N, Zhang K. B cells from subjects with CVI can be driven to Ig production in response to CD40 stimulation. Cell Immunol 1992;144:169-81.
74. 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 U S A 1994;91:1099-103.
75. Olerup O, Smith CIE, Bjorkander J, Hammarstrom L. Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. Proc Natl Acad Sci U S A 1992;89:10653-7.
76. Nonoyama S, Farrington M, Ishida H, et al. Activated B cells from patients with common variable immunodeficiency proliferate and synthesize immunoglobulin. J Clin Invest 1993;92:1282-7.
77. Eisenstein EM, Chua K, Strober W. B cell differentiation defects in common variable immunodeficiency are ameliorated after stimulation with anti-CD40 antibody and IL-10. J Immunol 1994;152:5957-68.
78. De Gast GC, Wilkins SR, Webster AD, et al. Functional 'immaturity' of isolated B cells from patients with hypogammaglobulinaemia. Clin Exp Immunol 1980;42:535-44.
79. Saiki O, Ralph P, Cunningham Rundles C, Good RA. Three distinct stages of B-cell defects in common varied hypogammaglobulinemia. Proc Natl Acad Sci U S A 1982; 79:6008-12.
80. Spickett GP, Matamoros N, Farrant J. Lymphocyte surface phenotype in common variable immunodeficiency. Dis Markers 1992;10:67-80.
81. Scott LJ, Bryant A, Webster DB, Farrant J. Failure in IgA secretion by surface IgA-positive B cells in common variable immunodeficiency. Clin Exp Immunol 1994;95:10-3.
82. Spickett GP, Farrant J, North ME, et al. Common variable immunodeficiency: how many diseases? Immunol Today 1997;18:325-8.
83. Cunningham Rundles C, Kazbay K, Hassett J, et al. 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.
84. Pandolfi F, Paganelli R, Cafaro A, et al. Abnormalities of lymphocyte subpopulations in CVI do not correlate with increased production of IL-6. Immunodeficiency 1993; 4:19-23.
85. Di Renzo M, Zhou Z, George I, et al. Enhanced apoptosis of T cells in common variable immunodeficiency (CVID): role of defective CD28 co-stimulation. Clin Exp Immunol 2000;120:503-11.
86. 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 2002;129:133-9.
87. Strannegard O, Bjorkander J, Hanson LA, Hermodsson S. Natural killer cells in common variable immunodeficiency and selective IgA deficiency. Clin Immunol Immunopathol 1982;25:325-34.
88. 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.
89. Kruger G, Welte K, Ciobanu N, et al. Interleukin-2 correction of defective in vitro T-cell mitogenesis in patients with common varied immunodeficiency. J Clin Immunol 1984; 4:295-303.
90. Sneller MC, Strober W. Abnormalities of lymphokine gene expression in patients with common variable immunodeficiency. J Immunol 1990;144:3762-9.
91. Vukmanovic S, Vuckovic S, Stosic-Grujicic S, et al. An unusual T-cell surface phenotype in vivo correlates with the failure to proliferate and produce IL-2 in vitro in a patient with common variable immunodeficiency. Clin Immunol Immunopathol 1992;65:261-70.
92. 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.
93. Lewkonia RM, Gairdner D, Doe WF. IgA deficiency in one of identical twins. BMJ 1976;1:311-3.
94. Hammarstrom L, Lonnqvist B, Ringden O, et al. Transfer of IgA deficiency to a bone-marrow-grafted patient with aplastic anaemia. Lancet 1985;i:778-81.
95. Ambrus M, Hernadi E, Bajtai G. Prevalence of HLA-A1 and HLA-B8 antigens in selective IgA deficiency. Clin Immunol Immunopathol 1977;7:311-4.
96. Strothman R, White MB, Testin J, et al. HLA and IgA deficiency in blood donors. Hum Immunol 1986;16:289-94.
97. Paganelli R, Scala E, Mezzaroma I, et al. Immunologic aspects of hyperimmunoglobulinemia E-like syndrome in patients with AIDS. J Allergy Clin Immunol 1995;95:995-1003.
98. Milner CM, Campbell RD. Genetic organization of the human MHC class III region. Front Biosci 2001;6:D914-26.
99. Wilton AN, Cobain TJ, Dawkins RL. Family studies of IgA deficiency. Immunogenetics 1985;21:333-42.
100. Kruskall MS, Marcus-Bagley D, Awdeh Z, et al. Many individuals with the MHC conserved extended [HLA-B8, SC01, DR3] haplotype have immunoglobulin deficiencies [abstract]. Clin Res 1993;41:277A.
101. Cucca F, Zhu ZB, Khanna A, et al. Evaluation of IgA deficiency in Sardinians indicates a susceptibility gene is encoded within the HLA class III region. Clin Exp Immunol 1998;111:76-80.
102. Schroeder HWJ, Zhu ZB, March RE, et al. Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes. Mol Med 1998;4:72-86.
103. de la Concha EG, Fernandez-Arquero M, Gual L, et al. MHC susceptibility genes to IgA deficiency are located in different regions on different HLA haplotypes. J Immunol 2002;169:4637-43.
104. Vorechovsky I, Cullen M, Carrington M, et al. 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 2000;164:4408-16.
105. Kralovicova J, Hammarstrom L, Plebani A, et al. Fine-scale mapping at IGAD1 and genome-wide genetic linkage analysis implicate HLA-DQ/DR as a major susceptibility locus in selective IgA deficiency and common variable immunodeficiency. J Immunol 2003;170:2765-75.
106. Murphy CC, Acton RT, Barger BO, et al. Population genetic analyses of insulin dependent diabetes mellitus using HLA allele frequencies. Clin Genet 1983;23:405-14.
107. Barton JC, Acton RT. HLA-A and -B alleles in hemochromatosis probands with HFE C282Y homozygosity in central Alabama. BMC Med Genet 2002;3:9-17.
108. Miller ME, Stiehm ER. Phagocytic, opsonic and immunoglobulin studies in newborns. Calif Med 1973;119:43-63.
109. Stiehm ER, Fudenberg HH. Serum levels of immune globulins in health and disease. A survey. Pediatrics 1966; 37:715-27.
110. De Greef GE, Van Tol MJ, Van Den Berg JW, et al. Serum immunoglobulin class and IgG subclass levels and the occurrence of homogeneous immunoglobulins during the course of ageing in humans. Mech Ageing Dev 1992;66:29-44.
111. Oxelius VA. IgG subclass levels in infancy and childhood. Acta Paediatr Scand 1979;68:23-7.
112. Conley ME, Rohrer J, Minegishi Y. X-linked agammaglobulinemia. Clin Rev Allergy Immunol 2000;19:183-204.
113. Montella L, Masci AM, Merkabaoui G, et al B-cell lymphopenia and hypogammaglobulinemia in thymoma patients. Ann Hematol 2003;82:343-7.
114. Durandy A. Hyper-IgM syndromes: a model for studying the regulation of class switch recombination and somatic hypermutation generation. Biochem Soc Trans 2002;30:815-8.
115. Lindberg K, Gustafson R, Samuelson A, Rynnel-Dagoo B. Impact of IgG replacement therapy and antibiotic treatment on the colonization of non-encapsulated Haemophilus influenzae in the nasopharynx in patients with hypogammaglobulinaemia. Scand J Infect Dis 2001;33:904-8.
116. NIH consensus conference. Intravenous immunoglobulin. Prevention and treatment of disease. JAMA 1990;264:3189-93.