J Korean Med Sci.  2010 Jun;25(6):824-828. 10.3346/jkms.2010.25.6.824.

Immunoglobulin G Subclass Deficiency is the Major Phenotype of Primary Immunodeficiency in a Korean Adult Cohort

• Kim JH
• Park HJ
• Choi GS
• Kim JE
• Ye YM
• Nahm DH
• Park HS

• KMID: 2150858
• DOI: http://doi.org/10.3346/jkms.2010.25.6.824

Abstract

Primary immunodeficiency disease (PID) is a rare disorder in adults. Most often, serious forms are detected during infancy or childhood. However, mild forms of PID may not be diagnosed until later in life, and some types of humoral immunodeficiency may occur in adulthood. The purpose of this study was to identify clinical features of PID in Korean adults. A retrospective study was performed on 55 adult patients who were diagnosed as PID between January 1998 and January 2009 at a single tertiary medical center in Korea. IgG subclass deficiency was the most common phenotype (67%, 37/55), followed by total IgG deficiency (20%, 11/55), IgM deficiency (7%, 4/55), common variable immunodeficiency (2%, 1/55), and X-linked agammaglobulinemia (2%, 1/55). IgG3 and IgG4 were the most affected subclasses. Upper and lower respiratory tract infections (76%) were the most frequently observed symptoms, followed by multiple site infection (11%), urinary tract infection, and colitis. Bronchial asthma, rhinitis, and several autoimmune diseases were common associated diseases. IgG and IgG subclass deficiency should be considered in adult patients presenting with recurrent upper and lower respiratory infections, particularly in those with respiratory allergies or autoimmune diseases.

Keyword

Adult; IgG Subclass Deficiency; Primary Immunodeficiency

Figure

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  Fig. 1 Distribution of primary immunodeficiency in adult patients from a single medical center in Korea.

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  Fig. 2 Affected IgG subclass of infectious complications (A) and underlying diseases (B) in patients with primary immunodeficiency disease.

Reference

1. Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol. 2007. 120:776–794.

2. Cunningham-Rundles C, Sidi P, Estrella L, Doucette J. Identifying undiagnosed primary immunodeficiency diseases in minority subjects by using computer sorting of diagnosis codes. J Allergy Clin Immunol. 2004. 113:747–755.

3. Kanoh T, Mizumoto T, Yasuda N, Koya M, Ohno Y, Uchino H, Yoshimura K, Ohkubo Y, Yamaguchi H. Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis. Vox Sang. 1986. 50:81–86.

4. Aghamohammadi A, Moein M, Farhoudi A, Pourpak Z, Rezaei N, Abolmaali K, Movahedi M, Gharagozlou M, Ghazi BM, Mahmoudi M, Mansouri D, Arshi S, Trash NJ, Akbari H, Sherkat R, Hosayni RF, Hashemzadeh A, Mohammadzadeh I, Amin R, Kashef S, Alborzi A, Karimi A, Khazaei H. Primary immunodeficiency in Iran: first report of the National Registry of PID in Children and Adults. J Clin Immunol. 2002. 22:375–380.

5. Leiva LE, Zelazco M, Oleastro M, Carneiro-Sampaio M, Condino-Neto A, Costa-Carvalho BT, Grumach AS, Quezada A, Patino P, Franco JL, Porras O, Rodriguez FJ, Espinosa-Rosales FJ, Espinosa-Padilla SE, Almillategui D, Martinez C, Tafur JR, Valentin M, Benarroch L, Barroso R, Sorensen RU. Primary immunodeficiency diseases in Latin America: the second report of the LAGID registry. J Clin Immunol. 2007. 27:101–108.

6. Reda SM, Afifi HM, Amine MM. Primary immunodeficiency diseases in Egyptian children: a single-center study. J Clin Immunol. 2009. 29:343–351.

7. Hayakawa H, Iwata T, Yata J, Kobayashi N. Primary immunodeficiency syndrome in Japan. I. Overview of a nationwide survey on primary immunodeficiency syndrome. J Clin Immunol. 1981. 1:31–39.

8. Lee JH, Sohn WY, Park HY, Hwang SJ, Seo WH, Kim SJ, Ahn SH, Jo EK, Ahn KM, Lee SI. A clinical study of primary immunodeficiency disease in a single center in Seoul from 1996 to 2004. Pediatr Allergy Respir Dis. 2005. 15:368–380.

9. Agarwal S, Cunningham-Rundles C. Assessment and clinical interpretation of reduced IgG values. Ann Allergy Asthma Immunol. 2007. 99:281–283.

10. Jolliff CR, Cost KM, Stivrins PC, Grossman PP, Nolte CR, Franco SM, Fijan KJ, Fletcher LL, Shriner HC. Reference intervals for serum IgG, IgA, IgM, C3, and C4 as determined by rate nephelometry. Clin Chem. 1982. 28:126–128.

11. Kirkpatrick P, Riminton S. Primary immunodeficiency diseases in Australia and New Zealand. J Clin Immunol. 2007. 27:517–524.

12. Joshi AY, Iyer VN, Hagan JB, St Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009. 84:16–22.

13. Abuzakouk M, Feighery C. Primary immunodeficiency disorders in the Republic of Ireland: first report of the national registry in children and adults. J Clin Immunol. 2005. 25:73–77.

14. Stray-Pedersen A, Abrahamsen TG, Froland SS. Primary immunodeficiency diseases in Norway. J Clin Immunol. 2000. 20:477–485.

15. 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. 2000. 164:4408–4416.

16. de Moraes Lui C, Oliveira LC, Diogo CL, Kirschfink M, Grumach AS. Immunoglobulin G subclass concentrations and infections in children and adolescents with severe asthma. Pediatr Allergy Immunol. 2002. 13:195–202.

17. Lock K, Anders S, Ernst M, Haas H, Zabel P. Immunoglobulin G subclass deficiency in patients with asthma and chronic obstructive bronchitis. Immun Infekt. 1990. 18:157–161.

18. Feldman C, Weltman M, Wadee A, Sussman G, Smith C, Zwi S. A study of immunoglobulin G subclass levels in black and white patients with various forms of obstructive lung disease. S Afr Med J. 1993. 83:9–12.

19. Soderstrom T, Soderstrom R, Enskog A. Immunoglobulin subclasses and prophylactic use of immunoglobulin in immunoglobulin G subclass deficiency. Cancer. 1991. 68:1426–1429.

20. Jefferis R, Kumararatne DS. Selective IgG subclass deficiency: quantification and clinical relevance. Clin Exp Immunol. 1990. 81:357–367.

21. Kim CH, Kim DG, Park SH, Choi JH, Lee CY, Hwang YI, Shin TR, Park SM, Park YB, Lee JY, Jang SH, Kim CH, Mo EK, Lee MG, Hyun IG, Jung KS. Incidence of immunoglobulin G subclass deficiencies in patients with bronchiectasis and the clinical characteristics of patients with immunoglobulin G subclass deficiency and bronchiectasis. Tuberc Respir Dis. 2009. 66:295–299.

22. Kay RA, Wood KJ, Bernstein RM, Holt PJ, Pumphrey RS. An IgG subclass imbalance in connective tissue disease. Ann Rheum Dis. 1988. 47:536–541.

23. Tamura A, Agematsu K, Urasawa R, Naganuma K, Komiyama A. Cardiac tamponade due to systemic lupus erythematosus in a 7-year-old boy with selective IgG subclass deficiency. Eur J Pediatr. 1998. 157:475–478.

24. Heiner DC. IgG subclass deficiencies: identifying and treating patients at risk. Vox Sang. 1986. 51:Suppl 2. 57–62.

25. Coskun Y, Bayraktaroglu Z. Immunoglobulin isotypes and IgG subclasses in recurrent infections. Turk J Pediatr. 1997. 39:347–352.

26. Pan Q, Hammarstrom L. Molecular basis of IgG subclass deficiency. Immunol Rev. 2000. 178:99–110.

27. Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005. 37:829–834.

28. Salzer U, Bacchelli C, Buckridge S, Pan-Hammarstrom Q, Jennings S, Lougaris V, Bergbreiter A, Hagena T, Birmelin J, Plebani A, Webster AD, Peter HH, Suez D, Chapel H, McLean-Tooke A, Spickett GP, Anover-Sombke S, Ochs HD, Urschel S, Belohradsky BH, Ugrinovic S, Kumararatne DS, Lawrence TC, Holm AM, Franco JL, Schulze I, Schneider P, Gertz EM, Schaffer AA, Hammarstrom L, Thrasher AJ, Gaspar HB, Grimbacher B. Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes. Blood. 2009. 113:1967–1976.

29. Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, Nelson RP Jr, Patel DD, Secord E, Sorensen RU, Wasserman RL, Cunningham-Rundles C. 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:S525–S553.

30. Abdou NI, Greenwell CA, Mehta R, Narra M, Hester JD, Halsey JF. Efficacy of intravenous gammaglobulin for immunoglobulin G subclass and/or antibody deficiency in adults. Int Arch Allergy Immunol. 2009. 149:267–274.