IgA Eksikliği ve Yaygın Değişken İmmün Yetmezlik

Öz

Selektif IgA eksikliği sIgAE ; sekretuvar IgA yokluğu ve serum IgA düzeyinin 5 mg/dl altında olması ile karakterize, en sık görülen immün yetmezliktir. IgAeksikliğinin patogenezi bilinmemekle birlikte, Ig sınıf değişimi ve sitokinlerindeiçinde olduğu izotip değişiminde anormallikler gösterilmiştir. Yaygın değişkenimmün yetmezlik YDİY , hipogamaglobulinemi, antikor yapımında bozukluk vetekrarlayan bakteriyel enfeksiyon ile karakterize, heterojen bir hastalık grubudur.Defektif T hücre aktivasyonu, tam fonksiyonel B hücre aktivasyonu için gerekliolan T ve B hücreler arasındaki ilişkiyi belirleyen CD40L ekspresyonundaki bozukluk ve/veya T hücre farklılaşmasında ihtiyaç duyulan sitokinlerin üretiminde anormalliklere yol açabilir. Bu da YDİY hastalarında bozulmuş sitokin üretimi açıklamalarından biri olan proliferasyon ve/veya farklılaşma bozukluklarına benzemektedir

Anahtar Kelimeler

• Selektif IgA eksikliği,yaygın değişken immün yetmezlik,hipogamaglobulinemi

Selective IgA Deficiency and Common Variable Immunodeficiency

Abstract

Selective IgA deficiency sIgAD , using 5 mg/dl of serum IgA as the upper limitfor diagnosis and concomitant lack of secretory IgA, is the most common formof primary immunodeficiency. The pathogenesis of IgA deficiency is not known,although abnormalities in Ig class switching and the cytokines involved in isotype switching have been implicated. Common Variable Immunodeficiency CVID is a heterogenous group of B cell deficiency syndromes characterized byhypogammaglobulinemia, impaired antibody production and recurrent bacterialinfections. Defective T-cell activation may lead to an impairment in cognate T-Bcell interaction due to impaired expression of CD40 ligand and/or abnormalitiesin the production of T-cell-derived cytokines required for fully functional B-cellactivation, proliferation and/or differentiation which could indeed explain theimpairment in antibody production present in CVID patients. It has been foundthat cytokines are produced in low levels due to the decreased T cell functionwhich occurs as a result of the defect in CD40L expression in CVID patients

Keywords

• Selective IgA deficiency,common variable immunodeficiency,hypogammaglobulinemia

Kaynakça

1. 1. Primary immunodeficiency diseases. Report of a WHO scientific group WHO. Clin Exp Immunol 1997;159:6236-41.
2. 2. Hammarström L, Smith CIE. Genetic approach to common variable immunodeficiency and IgA deficiency. In: Ochs H, Smith CIE, Puck J. Primary immunodeficiency disease a moleculer and genetic approach. Oxford: Oxford University Pres 2007;313-25.
3. 3. Cuningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol 2001;21:303-9.
4. 4. Quartier P. IgA deficiency. Arch Pediatr 2001;8:629-33.
5. 5. Aittoniemi J, Koskinen S, Laippala P, Laine S, Miettinen A. The significance IgG subclasses and manan-binding lectin (MBL) for susceptibility to infection in apparently healty adults with IgA deficiency. Clin Exp Immunol 1999;116:505-8.
6. 6. De Laat PCJ, Weermaes CMR, Gonnera R et al Clinical manifestations in selective IgA deficiency in chilhood. Acta Paediatr Scand 1991;80:798-804.
7. 7. Taylor B, Normal AP, Orgel HA et al. Transient IgA deficiency and pathogenesis of infantile atopy, Lancet, 1973:111-3.
8. 8. Ferreira A, Garcia Rodriguez MC, Lopez-Trascasa M et al, Anti-IgA antibodies in selective IgA deficiency and in primary immunodeficient patients treated with gamma-globulin. Clin Immunol Immunopathol 1988;47:199-207.

9. 9. Cuccia-Belvedere M, Monafo V, Martinetti M et al, Recurrentextended HLA haplotypes in children with selective IgA deficiency. Tissue Antigens 1989;34:127-32.
10. 10. Burgin-Wolff A, Gaze H, Hadziselimovic F, Huber H, Lentze MJ, Nussle D et al. Antigliadin and antiendomysium antibody determination for coeliac disease. C Arch Dis Child 1991;66:941-7.
11. 11. Camilleri JP, Moore RH, Griffiths DF, Wiliiams BD. Selective IgA deficiency associated with glomerulonephritis and oligoarhritis. Ann Rheum Dis 1992;51:123-5.
12. 12. Cerutti F, Urbino A, Sacchetti C, Palomba E, Zoppo M, Tovo PA. Selective IgA deficiency in juvenile-onset insulin dependent diabetes mellitus. Pediatr Med Chir 1988;10:197-201.
13. 13. Cunningham-Rundles C. Hematologic complications of primary immune deficiencies. Blood Rev 2002;16:61-4.
14. 14. Chapel HM, Webster ADB, Asesment of the immune system. Ochs HD, Smith CIE, Puck JM. Primary immunodeficiency diseases. A molecular and genetic approach. Oxford: Oxford University Pres 1999;419-31.
15. 15. Truedsson L, Baskin B, Pan Q, Rabbani H, Vorechovsky I, Smith CIE et al. Genetics of IgA deficiency. APMIS 1995;103:833-42.
16. 16. Hammarstörm L, Smith CIE, Berg U. Captopril induced IgA eficiency. Lancet 1991;336:436.
17. 17. Halliwell B, Gutteridge JMC, Cross CE. Free radicals, antioxidants, and human disease: Where are we now? J Lab Clin Med 1992;119:598-620.
18. 18. Hermaszewski RA, Webster ADB. Primary hypogammoglobulinemia: A survey of clinical manifestations and complications. QJ Med 1993;86:31-42.
19. 19. Ricardo U, Sorenson MD, Cleveland Moore MD. Antibody deficiency syndromes. 2000;47:1225-52.
20. 20. Fasano MB. Risk and benefit of intravenous immunoglobulin treatment in children. Curr Opin Pediatr 1995;7:688-94.
21. 21. Lewkonia RM, Gairdner D, Doe WF. IgA deficiency in one of identical twins. Br Med J 1976;1:311-3.
22. 22. Fasano MB, Sullivan KE, Sarpong SB. Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature. Medicine 1996;75:251-61.
23. 23. Cuningham-Rundles C. Common Variable immunodeficiency. In: Stiehm ER, Ochs HD, Winkelstein JA, eds. Immunologic Disorders in Infants and Children. 5th ed. Elsevier; 2004, 374-80.
24. 24. Nijenhuis T, Klasen I, Weemaes CM, et al. Common Variable immunodeficiency (CVID) in a family: an autosomal dominant mode of inheritance. Neth J Med 2001;59:134-9.
25. 25. Jin H, Webster AD, Vihinen M, et al. Identification of Btk mutations in 20 unrelated patients with X-linked agammaglobulinaemia (XLA). Hum Mol Genet 1995;4:693-700.
26. 26. Spriggs MK, Armitage RJ, Stockbine L,Clifford KY, Macduff BM, Sato TA et al. Recombinant human CD40 ligand Stimulates B cell proliferation and immunglobulin E secretion. J Exp Med 1992;176:1543-50.
27. 27. Clark EA, Ledbetter JA. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci USA 1986;83:4494-8.
28. 28. Castigli E, Geha RS. Molecular basis of common variable immunodeficiency. J Allergy Clin Immunol 2006;117:740-6.
29. 29. Kopecky O, Lukesova S. Genetic defects in common variable immunodefiency. Int J Immunogenet 2007;34:225-9.
30. 30. 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.
31. 31. Salzer U, Maul-Pavicic A, Cunningham- Rundels C, et al. ICOS deficiency in patients with common variable immunodeficiency. Clin Immunol 2004;113:234-40.
32. 32. 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.
33. 33. Garibyan L, Lobito AA, Siegel RM, et al. Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID). J Clin Invest 2007;117:1550-7.
34. 34. Goldacker S, Warnatz K. Tackling the heterogeneity of CVID. Curr Opin Allergy Clin Immunol 2005;5:504-9.
35. 35. Van Zelm MC, Reisli I, van der Burg M, et al. An antibodydeficiency syndrome due to mutations in the CD 19 gene. N Engl J Med 2006;354:1901-12.
36. 36. Kanegane H, Agematsu K, Futatani T et al. Novel mutations in a Japanese patient with CD19 deficiency. Genes Immun 2007;8:663-70.
37. 37. Knight AK, Radigan L, Marron T, et al. High serum levels of BAFF, APRIL, and TACI in common variable immunodeficiency. Clin Immunol 2007;124:182-9.
38. 38. Sarantopoulos S, Stevenson KE, Kim HT, et al. High levels of B-cell activating factor in patients with active chronic graftversus-host disease. Clin Cancer Res 2007;13:6107-14.
39. 39. Jaffe JS, Eisenstein E, Sneller MC, Strober W. T-cell abnormalities in common variable immunodeficiency. Pediatr Res 1993;33:24-8.
40. 40. North ME, Webster ADB, Farrant J. Defects in proliferative responses of T cells from patients with common variable immunodeficiency on direct activation of protein kinase C. Clin Exp Immunol 1991;85:198-201.
41. 41. Kruger G,Welte K, Ciobanu N, Cunningham-Rundles C, Ralph P, Venuta S, et al. Interleukin-2 correction of defective in vitro T-cell mitogenesis nin patiens with common varied immunodeficiency. J Clin Immunol 1984;4:295-303.
42. 42. Sneller MC, Strober W. Abnormalities of lymphokine gene expression in patiens with common variable immunodeficiency. J Immunol 1990;144:3762-9.
43. 43. Farrington M, Grosmaire LS, Nonoyama S, Fischer SH, Hollenbaugh D, Ledbetter JA, et al. CD40 ligand expression is defective in a subset of patients with common variable immunodeficiency. Proc Natl Acad Sci USA 1994;91:1099-1103.
44. 44. Gordon J, Millsum MJ, Guy GR, Ledbetter JA. Synergistic interaction between interleukin 4 and anti-Bp50 (CDw40) revealed in a novel B cell m restimulation assay. Eur J Immunol 1987;17:1535-8.
45. 45. Pastorelli G, Roncarolo MG, Touraine JL, Rousset F, Pene J, De Vries JE. Interleukin-4 suppresses immunoglobulin production by peripheral blood lymphocytes of patiens with common variable immunodeficiency (CVI) induced by supernatants of Tcell clones. Clin Exp Immunol 1989;78:341-7.
46. 46. Cunningham-Rundles C. Clinical and immunologic analyses of 103 patients with common variable immunodeficiency. J Clin Immunol 1989;9:22-33.
47. 47. Hausser C, Virelizer JL, Buriot D. Common variable hypogammaglobulinemia in children: Clinical and immunologic observations in 30 patiens. Am J Dis Child 1983;137:833-7
48. 48. Dukes RJ, Rosenow EC, Hermans PE. Pulmonary manifestations of hypogammaglobulinemia. Thorax 1978;33:603-7.
49. 49. Samuelson A, Borelli S, Gustafson R. Characterization of Haemophilus influenzae isolates from the respiratory track of patients with primary antibody deficiencies: Evidence for persistent colonizations. Scand J Infect Dis 1995;27:303-13.
50. 50. Buehring I, Friedrich B, Schaaf J, Schmidt H, Ahrens P, Zielen S. Chronic sinusitis refractory to Standard management in patients with humoral immunodeficiencies. Clin Exp Immunol 1997;109:468-72.
51. 51. Sicheree SH, Winkelstein JA. Primary immunodeficiency diseases in adults. JAMA 1998;279:58-61.
52. 52. Wheat WH, Cool CD, Morimoto Y, Rai PR, Kirkpatrick CH, Lindenbaum BA, et al. Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med 2005;202:479-84.
53. 53. Spickett GP. Current perspectives on common variable immunodeficiency. Clin Exp Allergy 2001;31:536-42.
54. 54. Rudge P, Webster AD, Revesz T, et al. Encephalomyelitis in primary hypogammaglobulinemia. Brain 1996;119:1-15.
55. 55. Sneller MC, Strober W, Eisenstein E, Jaffe JS. Cunningham Rundles C. New insights in to common variable immunodeficiency. Ann Intern Med 1993;1:118:720-30.
56. 56. Kinlen LJ, Webster ADB, Bird AG. Prospective study of cancer in patients with hypogammaglobulinemia. Lancet 1985;1:263-6.
57. 57. Cunningham-Rundles C, Siegal FP, Cuningham-Rundles S. Incidence of cancer in 98 patients with common variable immunodeficiency. J Clin Immunol 1987;7:294-9.
58. 58. Geha RS, Notarangelo LD, Casanova JL, et al. 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.
59. 59. Bonilla FA, Geha RS. Primary immunodeficiency diseases. J Allergy Clin Immunol 2003;111:5571-81.
60. 60. Orange JS, Hossny EM, Weiler CR, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2006;117:525-53.
61. 61. Thambakkul S, Bellow M. Replacement intravenous immune serum globulin therapy in patients with antibody immune deficiency. Immunol Allergy Clin North Am 2001;21:165-84.
62. 62. Gardulf A, Andersen V, Bjorkander J. Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs. Lancet 1995;345:365-9.
63. 63. Radinsky S, Bonagura V. Subcutaneous immunoglobulin infusion as an alternative to intravenous immunoglobulin. J Allergy Clin Immunol 2003;112:630-3.
64. 64. Jansen WT, Verel A, Beitsma M, et al. Longitudinal European surveillance study of antibiotic resistance of Haemophilus influenzae. J Antimicrob Chemother 2006;58:873-7.
65. 65. Riedel S, Beekmann SE, Heilmann KP, et al. Antimicrobial use in Europe and antimicrobial resistance in Streptococcus pneumoniae. Eur J Clin Microbiol Infect Dis 2007;26:485-90.
66. 66. Johnson DW, Stilwell MG, Fritsche TR, Jones RN. Emergence of multidrug-resistant Streptococcus pneumoniae: report from the SENTRY antimicrobial surveillance program (1999-2003). Diagn Microbiol Infect Dis 2006;56:69-74.
67. 67. Longhurst HJ, O'Grady C, Evans G, De Lord C, Hughes A, Cavenagh J et al. Anti-D immunoglobulin treatment for throm-bocytopenia associated with primary antibody deficiency. J Clin Pathol 2002;55:64-6.