J Korean Med Sci.  2016 Oct;31(10):1560-1565. 10.3346/jkms.2016.31.10.1560.

Immunoglobulin G Subclass Deficiencies in Adult Patients with Chronic Airway Diseases

• Kim JH
• Park S
• Hwang YI
• Jang SH
• Jung KS
• Sim YS
• Kim CH
• Kim C
• Kim DG

• KMID: 2468245
• DOI: http://doi.org/10.3346/jkms.2016.31.10.1560

Abstract

Immunoglobulin G subclass deficiency (IgGSCD) is a relatively common primary immunodeficiency disease (PI) in adults. The biological significance of IgGSCD in patients with chronic airway diseases is controversial. We conducted a retrospective study to characterize the clinical features of IgGSCD in this population. This study examined the medical charts from 59 adult patients with IgGSCD who had bronchial asthma or chronic obstructive pulmonary disease (COPD) from January 2007 to December 2012. Subjects were classified according to the 10 warning signs developed by the Jeffrey Modell Foundation (JMF) and divided into two patient groups: group I (n = 17) met ≥ two JMF criteria, whereas group II (n = 42) met none. IgG3 deficiency was the most common subclass deficiency (88.1%), followed by IgG4 (15.3%). The most common infectious complication was pneumonia, followed by recurrent bronchitis, and rhinosinusitis. The numbers of infections, hospitalizations, and exacerbations of asthma or COPD per year were significantly higher in group I than in group II (P < 0.001, P = 0.012, and P < 0.001, respectively). The follow-up mean forced expiratory volume (FEV1) level in group I was significantly lower than it was at baseline despite treatment of asthma or COPD (P = 0.036). In conclusion, IgGSCD is an important PI in the subset of patients with chronic airway diseases who had recurrent upper and lower respiratory infections as they presented with exacerbation-prone phenotypes, decline in lung function, and subsequently poor prognosis.

Keyword

Asthma; Chronic Obstructive Lung Diseases; IgG Subclass Deficiency; Respiratory Tract Infection

MeSH Terms

Adult
Aged
Asthma/complications/*diagnosis
Female
Forced Expiratory Volume
Humans
IgG Deficiency/complications/*diagnosis
Immunoglobulin G/classification
Klebsiella/isolation & purification
Male
Middle Aged
Moraxella (Branhamella) catarrhalis/isolation & purification
Pseudomonas aeruginosa/isolation & purification
Pulmonary Disease, Chronic Obstructive/complications/*diagnosis
Respiratory Function Tests
Respiratory Tract Infections/complications/microbiology
Retrospective Studies
Immunoglobulin G

Figure

• 

  Fig. 1 FEV1% predicted at baseline and follow-up visit in patients of group I and II.

Reference

1. Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008; 118:3546–3556.

2. Saturni S, Contoli M, Spanevello A, Papi A. Models of respiratory infections: virus-induced asthma exacerbations and beyond. Allergy Asthma Immunol Res. 2015; 7:525–533.

3. Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007; 370:786–796.

4. Holgate ST. Mechanisms of asthma and implications for its prevention and treatment: a personal journey. Allergy Asthma Immunol Res. 2013; 5:343–347.

5. Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010; 363:1128–1138.

6. Martínez-García MA, de la Rosa Carrillo D, Soler-Cataluña JJ, Donat-Sanz Y, Serra PC, Lerma MA, Ballestín J, Sánchez IV, Selma Ferrer MJ, Dalfo AR, et al. Prognostic value of bronchiectasis in patients with moderate-to-severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013; 187:823–831.

7. Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, Kobrynski LJ, Levinson AI, Mazer B, Nelson RP Jr, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005; 94:S1–63.

8. Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, Keller M, Kobrynski LJ, Komarow HD, Mazer B, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015; 136:1186–1205.e1-78.

9. Popa V. Airway obstruction in adults with recurrent respiratory infections and IgG deficiency. Chest. 1994; 105:1066–1072.

10. O'Keeffe S, Gzel A, Drury R, Cullina M, Greally J, Finnegan P. Immunoglobulin G subclasses and spirometry in patients with chronic obstructive pulmonary disease. Eur Respir J. 1991; 4:932–936.

11. Schwitzguébel AJ, Jandus P, Lacroix JS, Seebach JD, Harr T. Immunoglobulin deficiency in patients with chronic rhinosinusitis: Systematic review of the literature and meta-analysis. J Allergy Clin Immunol. 2015; 136:1523–1531.

12. Salmun LM, Barlan I, Wolf HM, Eibl M, Twarog FJ, Geha RS, Schneider LC. Effect of intravenous immunoglobulin on steroid consumption in patients with severe asthma: a double-blind, placebo-controlled, randomized trial. J Allergy Clin Immunol. 1999; 103:810–815.

13. Lehman H, Hernandez-Trujillo V, Ballow M. Diagnosing primary immunodeficiency: a practical approach for the non-immunologist. Curr Med Res Opin. 2015; 31:697–706.

14. Costa-Carvalho BT, Grumach AS, Franco JL, Espinosa-Rosales FJ, Leiva LE, King A, Porras O, Bezrodnik L, Oleastro M, Sorensen RU, et al. Attending to warning signs of primary immunodeficiency diseases across the range of clinical practice. J Clin Immunol. 2014; 34:10–22.

15. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, Gibson P, Ohta K, O'Byrne P, Pedersen SE, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008; 31:143–178.

16. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013; 187:347–365.

17. Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Franco JL, Gaspar HB, Holland SM, et al. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2014; 5:162.

18. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten CP, Gustafsson P, Hankinson J, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005; 26:948–968.

19. Popa V. ATS guidelines for methacholine and exercise challenge testing. Am J Respir Crit Care Med. 2001; 163:292–293.

20. Buckley RH. Immunoglobulin G subclass deficiency: fact or fancy? Curr Allergy Asthma Rep. 2002; 2:356–360.

21. Abrahamian F, Agrawal S, Gupta S. Immunological and clinical profile of adult patients with selective immunoglobulin subclass deficiency: response to intravenous immunoglobulin therapy. Clin Exp Immunol. 2010; 159:344–350.

22. Olinder-Nielsen AM, Granert C, Forsberg P, Friman V, Vietorisz A, Björkander J. Immunoglobulin prophylaxis in 350 adults with IgG subclass deficiency and recurrent respiratory tract infections: a long-term follow-up. Scand J Infect Dis. 2007; 39:44–50.

23. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R Jr, Castro M, Curran-Everett D, Fitzpatrick AM, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010; 181:315–323.

24. Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, Macnee W, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010; 182:598–604.

25. Weatherall M, Travers J, Shirtcliffe PM, Marsh SE, Williams MV, Nowitz MR, Aldington S, Beasley R. Distinct clinical phenotypes of airways disease defined by cluster analysis. Eur Respir J. 2009; 34:812–818.

26. Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, 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:S525–53.

27. 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.

28. Landwehr LP, Jeppson JD, Katlan MG, Esterl B, McCormick D, Hamilos DL, Gelfand EW. Benefits of high-dose i.v. immunoglobulin in patients with severe steroid-dependent asthma. Chest. 1998; 114:1349–1356.

29. Haque S, Boyce N, Thien FC, O'Hehir RE, Douglass J. Role of intravenous immunoglobulin in severe steroid-dependent asthma. Intern Med J. 2003; 33:341–344.