Journal of Clinical Immunology

, Volume 29, Issue 1, pp 130–136 | Cite as

IgA Deficiency: Correlation Between Clinical and Immunological Phenotypes

  • Asghar AghamohammadiEmail author
  • Taher Cheraghi
  • Mohammad Gharagozlou
  • Masoud Movahedi
  • Nima Rezaei
  • Mehdi Yeganeh
  • Nima Parvaneh
  • Hassan Abolhassani
  • Zahra Pourpak
  • Mostafa Moin



IgA deficiency (IGAD) is the most common primary antibody deficiency. Although many affected individuals have no apparent symptom, selected patients suffer from recurrent mucosal infections, allergies, and autoimmune diseases. We aimed to investigate the clinical features in relation to immune function of Iranian patients with symptomatic IGAD.


Thirty-seven patients (21 male and 16 female), aged 4–32 years, were evaluated in this study. Patients were followed for a total of 131 patient years with a mean follow-up of 3.5 years per patient.


The most prevalent presentations were recurrent infections occurring in 27 subjects, followed by allergy in eight cases and autoimmunity in two patients. However, during the follow-up period, 35 patients developed infections in respiratory and gastrointestinal tracts, necessitating medical care. Apart from infections, allergy was the most frequent complaint (31 cases); the major features were asthma, atopic dermatitis, and allergic rhinoconjunctivitis. Autoimmune diseases were documented in ten cases; thyroiditis was the most common. In 31 patients who received unconjugated pneumococcal polyvalent vaccine, antibody response against polysaccharide antigen was measured before and 28 days after vaccination. One fourth of vaccinated patients were hyporesponsive to vaccine; four of these patients developed bronchiectasis. The patients with IGAD were classified into two groups: group 1 (14 cases) consisted of patients with IGAD and other associated immune defects, such as immunoglobulin G (IgG) subclass deficiency and defective specific antibody production. Group 2 (23 cases) had isolated IGAD without other immunological abnormalities. There was a significantly increased number of lower respiratory tract infections in group 1 compared with group 2 (P = 0.006). Moreover, four patients of group 1 had bronchiectasis whereas none of the patients in group 2 developed this complication (P = 0.015).


Subclassification of IGAD regarding the existence of associated immune defects is useful in terms of morbidity and planning for medical care. IgA-deficient patients with concomitant immune defects such as defects in specific antibody production have higher rates of recurrent infections and bronchiectasis, which necessitates more effective monitoring.


Allergy antibody response autoimmunity IgA deficiency infection 


  1. 1.
    Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000;120(2):225–31. doi: 10.1046/j.1365-2249.2000.01131.x.PubMedCrossRefGoogle Scholar
  2. 2.
    Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005;94(5):S1–63.PubMedCrossRefGoogle Scholar
  3. 3.
    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(3):190–7. doi: 10.1006/clim.1999.4799.PubMedCrossRefGoogle Scholar
  4. 4.
    al-Attas RA, Rahi AH. Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia. J Clin Immunol. 1998;18(5):368–71. doi: 10.1023/A:1023247117133.PubMedCrossRefGoogle Scholar
  5. 5.
    Cunningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol. 2001;21(5):303–9. doi: 10.1023/A:1012241117984.PubMedCrossRefGoogle Scholar
  6. 6.
    Kanoh T, Mizumoto T, Yasuda N, et al. Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis. Vox Sang. 1986;50(2):81–6.PubMedGoogle Scholar
  7. 7.
    Schaffer FM, Monteiro RC, Volanakis JE, Cooper MD. IgA deficiency. Immunodefic Rev. 1991;3(1):15–44.PubMedGoogle Scholar
  8. 8.
    Burrows PD, Cooper MD. IgA deficiency. Adv Immunol. 1997;65:245–76. doi: 10.1016/S0065-2776(08)60744-0.PubMedCrossRefGoogle Scholar
  9. 9.
    Hanson LA, Bjorkander J, Carlsson B, Roberton D, Soderstrom T. The heterogeneity of IgA deficiency. J Clin Immunol. 1988;8(3):159–62. doi: 10.1007/BF00917561.PubMedCrossRefGoogle Scholar
  10. 10.
    Burgio GR, Duse M, Monafo V, Ascione A, Nespoli L. Selective IgA deficiency: clinical and immunological evaluation of 50 pediatric patients. Eur J Pediatr. 1980;133(2):101–6. doi: 10.1007/BF00441577.PubMedCrossRefGoogle Scholar
  11. 11.
    Crabbe PA, Heremans JF. The significance of local IgA in the physiology of the intestinal mucosa. Folia Med Neerl. 1969;12(3):100–6.PubMedGoogle Scholar
  12. 12.
    Heneghan MA, Stevens FM, Cryan EM, Warner RH, McCarthy CF. Celiac sprue and immunodeficiency states: a 25-year review. J Clin Gastroenterol. 1997;25(2):421–5. doi: 10.1097/00004836-199709000-00004.PubMedCrossRefGoogle Scholar
  13. 13.
    Sloper KS, Brook CG, Kingston D, Pearson JR, Shiner M. Eczema and atopy in early childhood: low IgA plasma cell counts in the jejunal mucosa. Arch Dis Child. 1981;56(12):939–42.PubMedCrossRefGoogle Scholar
  14. 14.
    Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clin Immunol. 2004;111(1):93–7. doi: 10.1016/j.clim.2003.12.005.PubMedCrossRefGoogle Scholar
  15. 15.
    Strober W, Sneller MC. IgA deficiency. Ann Allergy. 1991;66(5):363–75.PubMedGoogle Scholar
  16. 16.
    Wernette CM, Frasch CE, Madore D, et al. Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides. Clin Diagn Lab Immunol. 2003;10(4):514–9. doi: 10.1128/CDLI.10.4.514-519.2003.PubMedCrossRefGoogle Scholar
  17. 17.
    Vendrell M, de Gracia J, Rodrigo MJ, et al. Antibody production deficiency with normal IgG levels in bronchiectasis of unknown etiology. Chest 2005;127(1):197–204. doi: 10.1378/chest.127.1.197.PubMedCrossRefGoogle Scholar
  18. 18.
    Standardization of spirometry-1987 update. Statement of the American Thoracic Society. Am Rev Respir Dis. 1987;136(5):1285–98.Google Scholar
  19. 19.
    Aghamohammadi A, Mohammadi J, Parvaneh N, Rezaei N, Moin M, Espanol T, et al. Progression of selective IgA deficiency to common variable immunodeficiency. Int Arch Allergy Immunol 2008;147(2):87–92. doi: 10.1159/000135694.PubMedCrossRefGoogle Scholar
  20. 20.
    Schroeder HW Jr, 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(2):72–86.PubMedGoogle Scholar
  21. 21.
    Castigli E, Wilson SA, Garibyan L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet 2005;37(8):829–34. doi: 10.1038/ng1601.PubMedCrossRefGoogle Scholar
  22. 22.
    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(8):820–8. doi: 10.1038/ng1600.PubMedCrossRefGoogle Scholar
  23. 23.
    Hammarström LSC. Genetic approach to common variable immunodeficiency and IgA deficiency. In: Ochs HDSC, Puck JM, editors. Primary immunodeficiency diseases: a molecular and genetic approach. 2nd ed. New York: Oxford University Press; 2007. p. 313–25.Google Scholar
  24. 24.
    Rezaei N, Aghamohammadi A, Moin M, Pourpak Z, Movahedi M, Gharagozlou M, et al. Frequency and clinical manifestations of patients with primary immunodeficiency disorders in Iran: update from the Iranian Primary Immunodeficiency Registry. J Clin Immunol. 2006;26(6):519–32. doi: 10.1007/s10875-006-9047-x.PubMedCrossRefGoogle Scholar
  25. 25.
    Saghafi S, Pourpak Z, Aghamohammadi A, Pourfathollah AA, Samadian A, Farghadan M, et al. Selective immunoglobulin a deficiency in Iranian blood donors; prevalence, laboratory and clinical findings. Iran J Allergy Asthma Immunol. 2008;7(3):157–62.PubMedGoogle Scholar
  26. 26.
    Ozkan H, Atlihan F, Genel F, Targan S, Gunvar T. IgA and/or IgG subclass deficiency in children with recurrent respiratory infections and its relationship with chronic pulmonary damage. J Investig Allergol Clin Immunol. 2005;15(1):69–74.PubMedGoogle Scholar
  27. 27.
    Stead A, Douglas JG, Broadfoot CJ, Kaminski ER, Herriot R. Humoral immunity and bronchiectasis. Clin Exp Immunol. 2002;130(2):325–30. doi: 10.1046/j.1365-2249.2002.01974.x.PubMedCrossRefGoogle Scholar
  28. 28.
    Tabatabaie P, Aghamohammadi A, Mamishi S, Isaeian A, Heidari G, Abdollahzade S, MirSaeid Ghazi B, Yeganeh M, Cheraghi T, Abolhasani H, Saghafi S, Alizadeh H, Anaraki MR, et al. Evaluation of humoral immune function in patients with bronchiectasis. Iran J Allergy Asthma Immunol. 2008;7(2):69–77.PubMedGoogle Scholar
  29. 29.
    Stiehm RE. The four most common pediatric immunodeficiencies. Adv Exp Med Biol. 2007;601:15–26.PubMedGoogle Scholar
  30. 30.
    Golshan M, Mohamad-Zadeh Z, Zahedi-Nejad N, Rostam-Poor B. Prevalence of asthma and related symptoms in primary school children of Isfahan, Iran, in 1998. Asian Pac J Allergy Immunol. 2001;19(3):163–70.PubMedGoogle Scholar
  31. 31.
    Golshan M, Mohammad-Zadeh Z, Khanlar-Pour A, Iran-Pour R. Prevalence of asthma and related symptoms in junior high school children in Isfahan, Iran. Monaldi Arch Chest Dis. 2002;57(1):19–24.PubMedGoogle Scholar
  32. 32.
    Miri S, Farid R, Akbari H, Amin R. Prevalence of allergic rhinitis and nasal smear eosinophilia in 11- to 15 yr-old children in Shiraz. Pediatr Allergy Immunol. 2006;17(7):519–23. doi: 10.1111/j.1399-3038.2006.00424.x.PubMedCrossRefGoogle Scholar
  33. 33.
    Mirsaid Ghazi B, Imamzadehgan R, Aghamohammadi A, Darakhshan Davari R, Rezaei N. Frequency of allergic rhinitis in school-age children (7–18 Years) in Tehran. Iran J Allergy Asthma Immunol. 2003;2(4):181–4.PubMedGoogle Scholar
  34. 34.
    Ammann AJ, Hong R. Selective IgA deficiency: presentation of 30 cases and a review of the literature. Medicine 1971;60:223–36. doi: 10.1097/00005792-197105000-00004.CrossRefGoogle Scholar
  35. 35.
    Woof JM, Kerr MA. The function of immunoglobulin A in immunity. J Pathol. 2006;208(2):270–82. doi: 10.1002/path.1877.PubMedCrossRefGoogle Scholar
  36. 36.
    Bjorkander J, Bake B, Oxelius VA, Hanson LA. Impaired lung function in patients with IgA deficiency and low levels of IgG2 or IgG3. N Engl J Med. 1985;313(12):720–4.PubMedGoogle Scholar
  37. 37.
    Bossuyt X, Moens L, Van Hoeyveld E, et al. Coexistence of (partial) immune defects and risk of recurrent respiratory infections. Clin Chem. 2007;53(1):124–30. doi: 10.1373/clinchem.2007.075861.PubMedCrossRefGoogle Scholar
  38. 38.
    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(1):47–53.PubMedGoogle Scholar
  39. 39.
    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(24):1476–7.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Asghar Aghamohammadi
    • 1
    • 2
    • 3
    Email author
  • Taher Cheraghi
    • 1
  • Mohammad Gharagozlou
    • 1
    • 2
  • Masoud Movahedi
    • 1
    • 2
  • Nima Rezaei
    • 1
    • 2
  • Mehdi Yeganeh
    • 2
  • Nima Parvaneh
    • 1
    • 3
  • Hassan Abolhassani
    • 1
    • 3
  • Zahra Pourpak
    • 1
    • 2
  • Mostafa Moin
    • 1
    • 2
  1. 1.Department of Pediatrics, Division of Immunology and Allergy, Children Medical Center HospitalTehran University of Medical SciencesTehranIran
  2. 2.Immunology, Asthma, and Allergy Research Institute, Children Medical Center HospitalTehran University of Medical SciencesTehranIran
  3. 3.Growth and Development Research Center, Children Medical Center HospitalTehran University of Medical SciencesTehranIran

Personalised recommendations