Selective IgA deficiency and allergic diseases: Clinical and immunological evaluation
Main Article Content
Keywords
allergic diseases, immunglobulin E, selective IgA deficiency
Abstract
Purpose: We aimed to investigate allergic sensitization and associated factors in pediatric patients with selective immunoglobulin A deficiency (SIgAD) and to evaluate differences between allergic and nonallergic groups.
Methods: We analyzed 110 patients (aged 4–18 years) diagnosed with SIgAD at Çam and Sakura City Hospitals, Istanbul, between 2021 and 2024. Their demographic, clinical, and laboratory data were assessed.
Results: Allergic sensitization was detected in 62.7% of patients. Patients with allergic sensitization, family history of allergic diseases, eosinophilia, and elevated total immunoglobulin E (IgE) levels were significantly higher (P < 0.05). Immunglobulin M (IgM) levels were higher in the allergic group (P = 0.01), and they had lower neutrophil counts (P = 0.03). Allergic sensitization was lower in patients with autoimmune diseases (P = 0.03). In 60% of the patients, the main reason for presentation was recurrent infection.
Conclusion: Allergic sensitization with SIgAD is associated with genetic and immunological factors. A family history of allergic disease, eosinophilia, and elevated total IgE levels are important markers for the development of allergy. These findings highlight the need to closely monitor allergies in people with SIgAD.
References
1 Yel L. Selective IgA deficiency. J Clin Immunol. 2010;30:10–16. 10.1007/s10875-009-9357-x
2 Wang N, Hammarström L. IgA deficiency: What is new? Curr Opin Allergy Clin Immunol. 2012;12:602–8. 10.1097/ACI.0b013e3283594219
3 Yazdani R, Azizi G, Abolhassani H, Aghamohammadi A. Selective IgA deficiency: Epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management. Scand J Immunol. 2017;85:3–12. 10.1111/sji.12499
4 Karaca NE, Severcan EU, Bilgin BG, Azarsiz E, Akarcan S, Gunaydın NC, et al. Familial inheritance and screening of first-degree relatives in common variable immunodeficiency and immunoglobulin A deficiency patients. Int J Immunopathol Pharmacol. 2018;32:2058738418779458. 10.1177/2058738418779458
5 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;147:87–92. 10.1159/000135694
6 Woof JM, Kerr MA. The function of immunoglobulin A in immunity. J Pathol. 2006;208:270–82. 10.1002/path.1877
7 Aghamohammadi A, Abolhassani H, Biglari M, Abolmaali S, Moazzami K, Tabatabaeiyan M, et al. Analysis of switched memory B cells in patients with IgA deficiency. Int Arch Allergy Immunol. 2011;156:462–8. 10.1159/000323903
8 Nechvatalova J, Pikulova Z, Stikarovska D, Pesak S, Vlkova M, Litzman J. B-lymphocyte subpopulations in patients with selective IgA deficiency. J Clin Immunol. 2012;32:441–8. 10.1007/s10875-012-9655-6
9 Cunningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol. 2001;21:303–9. 10.1023/a:1012241117984
10 Bagheri Y, Sanaei R, Yazdani R, Shekarabi M, Falak R, Mohammadi J, et al. The heterogeneous pathogenesis of selective immunoglobulin A deficiency. Int Arch Allergy Immunol. 2019;179:231–46. 10.1159/000499044
11 Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. European Society for Immunodeficiencies, 2019, Jan 22. ESID Registry—Working definitions for clinical diagnosis of PID. J Allergy Clin Immunol Pract. 2019;7(6):1763–70. 10.1016/j.jaip.2019.02.004
12 Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, et al. Global Initiative for Asthma Strategy 2021, Executive summary and rationale for key changes. Am J Respir Crit Care Med. 2022;205(1):17–35. 10.1164/rccm.202109-2205PP
13 Bousquet J, Toumi M, Pinto BS. The Allergic Rhinitis and Its Impact on Asthma (ARIA) approach of value-added medicines: As-needed treatment in allergic rhinitis. J Allergy Clin Immunol Pract. 2022;10(11):2878–88. 10.1016/j.jaip.2022.07.020
14 Santos AF, Riggioni C, Agache I, Akdis CA, Akdis M, Alvarez-Perea A, et al. EAACI guidelines on the management of IgE-mediated food allergy. Allergy. 2025;80(1):14–36. 10.1111/all.16345
15 Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 1980;60(92):44–47. 10.2340/00015555924447
16 Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burneyet PG, et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012;67(1):18–24. 10.1111/j.13989995.2011.02728.x
17 Swain S, Selmi C, Gershwin ME, Teuber SS. The clinical implications of selective IgA deficiency. J Transl Autoimmun. 2019;2:100025. 10.1016/j.jtauto.2019.100025
18 Erkoçoğlu M, Metin A, Kaya A, Özcan C, Akan A, Civelek E, et al. Allergic and autoimmune disorders in families with selective IgA deficiency. Turk J Med Sci. 2017;47:592–8. 10.3906/sag-1605-50
19 Delavari S, Shad TM, Shariati S, Salami F, Rasouli S. Allergy in patients with selective IgA deficiency. Immunol Genet J. 2020;3:54–63. 10.22034/igj.2020.224572.1035
20 Jacob CM, Pastorino AC, Fahl K, Carneiro-Sampaio M, Monteiro RC. Autoimmunity in IgA deficiency: Revisiting the role of IgA as a silent housekeeper. J Clin Immunol. 2008;1:S56–S61. 10.1007/s10875-007-9163-2
21 Breedveld A, van Egmond M. IgA and FcαRI: Pathological roles and therapeutic opportunities. Front Immunol. 2019;10:553. 10.3389/fimmu.2019.00553
22 Shirakawa T, Enomoto T, Shimazu S, Hopkin JM. The inverse association between tuberculin responses and atopic disorder. Science. 1997;275:77–9. 10.1126/science.275.5296.77
23 Robinson DS, Larché M, Durham SR. Tregs and allergic disease. J Clin Investig. 2004;114:1389–97. 10.1172/JCI23595
24 Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012;18:673–83. 10.1038/nm.2731
25 Mucha SM, Baroody FM. Relationships between atopy and bacterial infections. Curr Allergy Asthma Rep. 2003;3:232–7. 10.1007/s11882-003-0045-2
26 Juhn YJ. Risks for infection in patients with asthma (or other atopic conditions): Is asthma more than a chronic airway disease? J Allergy Clin Immunol. 2014;134:247–57. 10.1016/j.jaci.2014.04.024
27 Custovic A, Murray C, Simpson A. Allergy and infection: Understanding their relationship. Allergy. 2005;60(Suppl. S79):10–13. 10.1111/j.1398-9995.2005.00851.x
28 Murphy K, Weaver C, Janeway’s immunobiology. 9th ed. London, NY: Garland Science; 2016. 425 p.
29 Macpherson AJ, Yilmaz B, Limenitakis JP. IgA function in relation to the intestinal microbiota. Ann Rev Immunol. 2018;36:359–81. 10.1146/annurev-immunol-042617-053238
30 Lycke NY, Bemark M. The regulation of gut mucosal IgA B-cell responses: Recent developments. Mucosal Immunol. 2017;10:1361–74. 10.1038/mi.2017.62
31 Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal Immunol. 2011;4:590–7. 10.1038/mi.2011.39
32 Durham SR, Shamji MH. Alerjen immunotherapy: Past, present, and future. Nat Rev Immunol. 2023;23(5):317–28. 10.1038/s41577-022-00786-1
33 Orivuori L, Loss G, Roduit C. Soluble immunoglobulin A in breast milk is inversely associated with atopic dermatitis at early age: The PASTURE cohort study. Clin Exp Allergy. 2014;44:102–12. 10.1111/cea.12199
34 Savilahti E, Siltanen M, Kajosaari M. IgA antibodies, TGF-beta1 and-beta2, and soluble CD14 in the colostrum and development of atopy by age 4. Pediatr Res. 2005;58:1300–5. 10.1203/01.pdr.0000183784.87452.c6
35 Iyengar SR, Walker WA. Immune factors in breast milk and the development of atopic disease. J Pediatr Gastroenterol Nutr. 2012;55:641–7. 10.1097/MPG.0b013e3182617a9d
36 Boyle RJ, Ismail IH, Kivivuori S. Lactobacillus GG treatment during pregnancy for the prevention of eczema: A randomized controlled trial. Allergy. 2011;66:509–16. 10.1111/j.1398-9995.2010.02507.x
37 Savilahti E, Tainio VM, Salmenpera L. Levels of IgA and cow milk antibodies in breast milk vs. the development of atopy in children. Low colostral IgA associated with cow milk allergy. Adv Exp Med Biol. 1991;310:417–25. 10.1007/978-1-4615-3838-7_54
38 Aghamohammadi A, Cheraghi T, Gharagozlou M, Movahedi M, Rezaei N, Yeganeh M, et al. IgA deficiency: Correlation between clinical and immunological phenotypes. J Clin Immunol. 2009;29:130–6. 10.1007/s10875-008-9229-9
39 Yazdani R, Latif A, Tabassomi F, Abolhassani, H, Azizi, G, Rezaei N, et al. Clinical phenotype classification for selective immunoglobulin A deficiency. Expert Rev Clin Immunol. 2015;11:1245–54. 10.1586/1744666X.2015.1081565
40 Jorgensen GH, Gardulf A, Sigurdsson MI, Sigurdardottir ST, Thorsteinsdottir I, Gudmundsson S, et al. Clinical symptoms in adults with selective IgA deficiency: A case-control study. J Clin Immunol. 2013;33:742–7. 10.1007/s10875-012-9858-x
41 Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: Clinical correlates and responses to pneumococcal vaccine. Clin Immunol. 2004;111:93–7. 10.1016/j.clim.2003.12.005
42 Lougaris V, Sorlini A, Monfredini C, Ingrasciotta G, Caravaggio A, Lorenzini T, et al. Clinical and laboratory features of 184 Italian pediatric patients affected with selective IgA deficiency (SIgAD): A longitudinal single-center study. J Clin Immunol. 2019;39:470–5. 10.1007/s10875-019-00647-y
43 Domínguez O, Giner MT, Alsina L, Martín MA, Lozano J, Plaza AM. Fenotipos clínicos asociados a la deficiencia selectiva de IgA revisión de 330 casos y propuesta de un protocolo de seguimiento. An Pediatr (Barc). 2012;76:261–7. 10.1016/j.anpedi.2011.11.006
44 Magen E, Masalha A, Waitman DA, Kahan N, Viner I, Klassov L, et al. Prevalence of dermatologic diseases among patients with selective immunoglobulin A deficiency. Allergy Asthma Proc. 2017;38:70–7. 10.2500/aap.2017.38.4018
45 Janzi M, Kull I, Sjöberg R, Wan J, Melén E, Bayat N, et al. Selective IgA deficiency in early life: Association to infections and allergic diseases during childhood. Clin Immunol. 2009;133:78–85. 10.1016/j.clim.2009.05.014
46 Aytekin C, Tuygun N, Gokce S, Dogu F, Ikinciogullari A. Selective IgA deficiency: Clinical and laboratory features of 118 children in Turkey. J Clin Immunol. 2012;32:961–6. 10.1007/s10875-012-9702-3
47 Moschese V, Chini L, Graziani S, Sgrulletti M, Gallo V, Di Matteo G, et al. Follow-up and outcome of symptomatic partial or absolute IgA deficiency in children. Eur J Pediatr. 2019;178(1):51–60. 10.1007/s00431-018-3248-1
48 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;133:101–6. 10.1007/BF00441577
49 Živković J, Lipej M, Banić I, Bulat Lokas S, Nogalo B, Lulić Jurjević R, et al. Respiratory and allergic disorders in children with severe and partial immunoglobulin A immunodeficiency. Scand J Immunol. 2019;90:e12828. 10.1111/sji.12828
50 Gualdi G, Lougaris V, Baronio M, Vitali M, Tampella G, Moratto D, et al. Burden of skin disease in selective IgA deficiency and common variable immunodeficiency. J Investig Allergol Clin Immunol. 2015;25(5):369–71.
51 Papadopoulou A, Mermiri D, Taousani S, Triga M, Nicolaidou P, Priftis KN. Bronchial hyper-responsiveness in selective IgA deficiency. Pediatr Allergy Immunol. 2005;16:495–500. 10.1111/j.1399-3038.2005.00316.x
52 Abolhassani H, Gharib B, Shahinpour S, Masoom SN, Havaei A, Mirminachi B, et al. Autoimmunity in patients with selective IgA deficiency. J Investig Allergol Clin Immunol. 2015;25:112–9.
53 Shkalim V, Monselize Y, Segal N, Zan-Bar I, Hoffer V, Garty BZ. Selective IgA deficiency in children in Israel. J Clin Immunol. 2010;30:761–5. 10.1007/s10875-010-9438-x
54 Plebani A, Monafo V, Ugazio AG, Monti C, Avanzini MA, Massimi P, et al. Comparison of the frequency of atopic diseases in children with severe and partial IgA deficiency. Int Arch Allergy Immunol. 1987;82:485–6. 10.1159/000234261
55 Wang W, Yao T, Zhang T, Quan M, Wang C, Zhang L, et al. Selective immunoglobulin A deficiency (SIgAD) primarily leads to recurrent infections and autoimmune diseases: A retrospective study of Chinese patients in the past 40 years. Genes Dis. 2020;7:115–21. 10.1016/j.gendis.2019.10.014
56 De Laat PC, Weemaes CM, Gonera R, Van Munster PJ, Bakkeren JA, Stoelinga GB. Clinical manifestations in selective IgA deficiency in childhood. A follow-up report. Acta Paediatr. 1991;80:798–804. 10.1111/j.1651-2227.1991.tb11952.x
57 Sandin A, Björkstén B, Böttcher MF, Englund E, Jenmalm MC, Bråbäck L. High salivary secretory IgA antibody levels are associated with less late-onset wheezing in IgE-sensitized infants. Pediatr Allergy Immunol. 2011;22:477–81. 10.1111/j.1399-3038.2010.01106.x
58 Aksu KAM, Asilsoy S et al. Approach to diagnosis and treatment of atopic dermatitis: National Guide 2018. Asthma Allergy Immunol. 2018;16(2):1–95. 10.4274/turkderm.87143
59 Serbes M, Özkan B, Can D, Meşe T, et al. Skin allergies. Izmir Behçet Uz Children’s Hospital Pediatrics, Ankara: Nobel Medicine Bookstores; 2022. pp. 514–23.
60 Strait RT, Mahler A, Hogan S, Khodoun M, Shibuya A, Finkelman FD. Ingested allergens must be absorbed systemically to induce systemic anaphylaxis. J Allergy Clin Immunol. 2011;127:982–989.e1. 10.1016/j.jaci.2011.01.034
61 Szczawińska-Popłonyk A, Bręborowicz A, Ossowska L. Food allergy in children with hypogammaglobulinemia. Pediatr Pol. 2012;87:444–8. 10.1016/j.pepo.2012.07.004
62 Heeb LEM, Egholm C, Boyman O. Evolution and function of interleukin-4 receptor signaling in adaptive immunity and neutrophils. Genes Immun. 2020;21:143–9. 10.1038/s41435-020-0095-7
63 Patel DF, Peiró T, Bruno N, Vuononvirta J, Akthar S, Puttur F, et al. Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation. Sci Immunol. 2019;4(41):eaax7006. 10.1126/sciimmunol.aax7006
64 Woytschak J, Keller N, Krieg C, Impellizzieri D, Thompson RW, Wynn TA, et al. Type 2 interleukin-4 receptor signaling in neutrophils antagonizes their expansion and migration during infection and inflammation. Immunity. 2016;45:172–84. 10.1016/j.immuni.2016.06.025
65 Brandtzaeg P, Nilssen DE. Mucosal aspects of primary B-cell deficiency and gastrointestinal infections. Curr Opin Gastroenterol. 1995;11:532–40. 10.1111/j.1749-6632.2002.tb04131.x
66 Brandtzaeg P, Karlsson G, Hansson G, Petruson B, Björkander J, Hanson L. The clinical condition of IgA-deficient patients is related to the proportion of IgD-and IgM-producing cells in their nasal mucosa. Clin Exp Immunol. 1987;67(3):626.
67 Kanok JM, Steinberg P, Cassidy JT, Petty RE, Bayne NK. Serum IgE levels in patients with selective IgA deficiency. Ann Allergy. 1978;41:22–3.
68 Burks AW, Sampson HA, Buckley RH. Anaphylactic reactions after gamma globulin administration in patients with hypogammaglobulinemia. N Engl J Med. 1986;314:560–4. 10.1056/NEJM198602273140907
69 Pearce N, Aït-Khaled N, Beasley R, Mallol J, Keil U, Mitchell E, et al. Worldwide trends in the prevalence of asthma symptoms: Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2007;62(9):758–66. 10.1136/thx.2006.070169
70 Akçay A, Tamay Z, Hocaoğlu AB, Ergin A, Güler N. Risk factors affecting asthma prevalence in adolescents living in Istanbul, Turkey. Allergol Immunopathol (Madr). 2014;42(5):449–58. 10.1016/j.aller.2013.05.005
71 Rebelo Gomes E, Fonseca J, Araujo L, Demoly P. Drug allergy claims in children: From self-reporting to confirmed diagnosis. Clin Exp Allergy. 2008;38(1):191–8. 10.1111/j.1365-2222.2007.02870.x
72 Erkoçoğlu M, Kaya A, Civelek E, Ozcan C, Cakır B, Akan A, et al. Prevalence of confirmed immediate type drug hypersensitivity reactions among school children. Pediatr Allergy Immunol. 2013;24(2):160–7. 10.1111/pai.12047
73 Meerwaldt R, Odink RJ, Landaeta R, Aarts F, Brunekreef B, Gerritsen J, et al. A lower prevalence of atopy symptoms in children with type 1 diabetes mellitus. Clin Exp Allergy. 2002;32(2).254–5. 10.1046/j.13652222.2002.01311.x
74 Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136:1186–1205.e78. 10.1016/j.jaci.2015.04.049
2 Wang N, Hammarström L. IgA deficiency: What is new? Curr Opin Allergy Clin Immunol. 2012;12:602–8. 10.1097/ACI.0b013e3283594219
3 Yazdani R, Azizi G, Abolhassani H, Aghamohammadi A. Selective IgA deficiency: Epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management. Scand J Immunol. 2017;85:3–12. 10.1111/sji.12499
4 Karaca NE, Severcan EU, Bilgin BG, Azarsiz E, Akarcan S, Gunaydın NC, et al. Familial inheritance and screening of first-degree relatives in common variable immunodeficiency and immunoglobulin A deficiency patients. Int J Immunopathol Pharmacol. 2018;32:2058738418779458. 10.1177/2058738418779458
5 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;147:87–92. 10.1159/000135694
6 Woof JM, Kerr MA. The function of immunoglobulin A in immunity. J Pathol. 2006;208:270–82. 10.1002/path.1877
7 Aghamohammadi A, Abolhassani H, Biglari M, Abolmaali S, Moazzami K, Tabatabaeiyan M, et al. Analysis of switched memory B cells in patients with IgA deficiency. Int Arch Allergy Immunol. 2011;156:462–8. 10.1159/000323903
8 Nechvatalova J, Pikulova Z, Stikarovska D, Pesak S, Vlkova M, Litzman J. B-lymphocyte subpopulations in patients with selective IgA deficiency. J Clin Immunol. 2012;32:441–8. 10.1007/s10875-012-9655-6
9 Cunningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol. 2001;21:303–9. 10.1023/a:1012241117984
10 Bagheri Y, Sanaei R, Yazdani R, Shekarabi M, Falak R, Mohammadi J, et al. The heterogeneous pathogenesis of selective immunoglobulin A deficiency. Int Arch Allergy Immunol. 2019;179:231–46. 10.1159/000499044
11 Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. European Society for Immunodeficiencies, 2019, Jan 22. ESID Registry—Working definitions for clinical diagnosis of PID. J Allergy Clin Immunol Pract. 2019;7(6):1763–70. 10.1016/j.jaip.2019.02.004
12 Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, et al. Global Initiative for Asthma Strategy 2021, Executive summary and rationale for key changes. Am J Respir Crit Care Med. 2022;205(1):17–35. 10.1164/rccm.202109-2205PP
13 Bousquet J, Toumi M, Pinto BS. The Allergic Rhinitis and Its Impact on Asthma (ARIA) approach of value-added medicines: As-needed treatment in allergic rhinitis. J Allergy Clin Immunol Pract. 2022;10(11):2878–88. 10.1016/j.jaip.2022.07.020
14 Santos AF, Riggioni C, Agache I, Akdis CA, Akdis M, Alvarez-Perea A, et al. EAACI guidelines on the management of IgE-mediated food allergy. Allergy. 2025;80(1):14–36. 10.1111/all.16345
15 Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 1980;60(92):44–47. 10.2340/00015555924447
16 Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burneyet PG, et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012;67(1):18–24. 10.1111/j.13989995.2011.02728.x
17 Swain S, Selmi C, Gershwin ME, Teuber SS. The clinical implications of selective IgA deficiency. J Transl Autoimmun. 2019;2:100025. 10.1016/j.jtauto.2019.100025
18 Erkoçoğlu M, Metin A, Kaya A, Özcan C, Akan A, Civelek E, et al. Allergic and autoimmune disorders in families with selective IgA deficiency. Turk J Med Sci. 2017;47:592–8. 10.3906/sag-1605-50
19 Delavari S, Shad TM, Shariati S, Salami F, Rasouli S. Allergy in patients with selective IgA deficiency. Immunol Genet J. 2020;3:54–63. 10.22034/igj.2020.224572.1035
20 Jacob CM, Pastorino AC, Fahl K, Carneiro-Sampaio M, Monteiro RC. Autoimmunity in IgA deficiency: Revisiting the role of IgA as a silent housekeeper. J Clin Immunol. 2008;1:S56–S61. 10.1007/s10875-007-9163-2
21 Breedveld A, van Egmond M. IgA and FcαRI: Pathological roles and therapeutic opportunities. Front Immunol. 2019;10:553. 10.3389/fimmu.2019.00553
22 Shirakawa T, Enomoto T, Shimazu S, Hopkin JM. The inverse association between tuberculin responses and atopic disorder. Science. 1997;275:77–9. 10.1126/science.275.5296.77
23 Robinson DS, Larché M, Durham SR. Tregs and allergic disease. J Clin Investig. 2004;114:1389–97. 10.1172/JCI23595
24 Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012;18:673–83. 10.1038/nm.2731
25 Mucha SM, Baroody FM. Relationships between atopy and bacterial infections. Curr Allergy Asthma Rep. 2003;3:232–7. 10.1007/s11882-003-0045-2
26 Juhn YJ. Risks for infection in patients with asthma (or other atopic conditions): Is asthma more than a chronic airway disease? J Allergy Clin Immunol. 2014;134:247–57. 10.1016/j.jaci.2014.04.024
27 Custovic A, Murray C, Simpson A. Allergy and infection: Understanding their relationship. Allergy. 2005;60(Suppl. S79):10–13. 10.1111/j.1398-9995.2005.00851.x
28 Murphy K, Weaver C, Janeway’s immunobiology. 9th ed. London, NY: Garland Science; 2016. 425 p.
29 Macpherson AJ, Yilmaz B, Limenitakis JP. IgA function in relation to the intestinal microbiota. Ann Rev Immunol. 2018;36:359–81. 10.1146/annurev-immunol-042617-053238
30 Lycke NY, Bemark M. The regulation of gut mucosal IgA B-cell responses: Recent developments. Mucosal Immunol. 2017;10:1361–74. 10.1038/mi.2017.62
31 Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal Immunol. 2011;4:590–7. 10.1038/mi.2011.39
32 Durham SR, Shamji MH. Alerjen immunotherapy: Past, present, and future. Nat Rev Immunol. 2023;23(5):317–28. 10.1038/s41577-022-00786-1
33 Orivuori L, Loss G, Roduit C. Soluble immunoglobulin A in breast milk is inversely associated with atopic dermatitis at early age: The PASTURE cohort study. Clin Exp Allergy. 2014;44:102–12. 10.1111/cea.12199
34 Savilahti E, Siltanen M, Kajosaari M. IgA antibodies, TGF-beta1 and-beta2, and soluble CD14 in the colostrum and development of atopy by age 4. Pediatr Res. 2005;58:1300–5. 10.1203/01.pdr.0000183784.87452.c6
35 Iyengar SR, Walker WA. Immune factors in breast milk and the development of atopic disease. J Pediatr Gastroenterol Nutr. 2012;55:641–7. 10.1097/MPG.0b013e3182617a9d
36 Boyle RJ, Ismail IH, Kivivuori S. Lactobacillus GG treatment during pregnancy for the prevention of eczema: A randomized controlled trial. Allergy. 2011;66:509–16. 10.1111/j.1398-9995.2010.02507.x
37 Savilahti E, Tainio VM, Salmenpera L. Levels of IgA and cow milk antibodies in breast milk vs. the development of atopy in children. Low colostral IgA associated with cow milk allergy. Adv Exp Med Biol. 1991;310:417–25. 10.1007/978-1-4615-3838-7_54
38 Aghamohammadi A, Cheraghi T, Gharagozlou M, Movahedi M, Rezaei N, Yeganeh M, et al. IgA deficiency: Correlation between clinical and immunological phenotypes. J Clin Immunol. 2009;29:130–6. 10.1007/s10875-008-9229-9
39 Yazdani R, Latif A, Tabassomi F, Abolhassani, H, Azizi, G, Rezaei N, et al. Clinical phenotype classification for selective immunoglobulin A deficiency. Expert Rev Clin Immunol. 2015;11:1245–54. 10.1586/1744666X.2015.1081565
40 Jorgensen GH, Gardulf A, Sigurdsson MI, Sigurdardottir ST, Thorsteinsdottir I, Gudmundsson S, et al. Clinical symptoms in adults with selective IgA deficiency: A case-control study. J Clin Immunol. 2013;33:742–7. 10.1007/s10875-012-9858-x
41 Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: Clinical correlates and responses to pneumococcal vaccine. Clin Immunol. 2004;111:93–7. 10.1016/j.clim.2003.12.005
42 Lougaris V, Sorlini A, Monfredini C, Ingrasciotta G, Caravaggio A, Lorenzini T, et al. Clinical and laboratory features of 184 Italian pediatric patients affected with selective IgA deficiency (SIgAD): A longitudinal single-center study. J Clin Immunol. 2019;39:470–5. 10.1007/s10875-019-00647-y
43 Domínguez O, Giner MT, Alsina L, Martín MA, Lozano J, Plaza AM. Fenotipos clínicos asociados a la deficiencia selectiva de IgA revisión de 330 casos y propuesta de un protocolo de seguimiento. An Pediatr (Barc). 2012;76:261–7. 10.1016/j.anpedi.2011.11.006
44 Magen E, Masalha A, Waitman DA, Kahan N, Viner I, Klassov L, et al. Prevalence of dermatologic diseases among patients with selective immunoglobulin A deficiency. Allergy Asthma Proc. 2017;38:70–7. 10.2500/aap.2017.38.4018
45 Janzi M, Kull I, Sjöberg R, Wan J, Melén E, Bayat N, et al. Selective IgA deficiency in early life: Association to infections and allergic diseases during childhood. Clin Immunol. 2009;133:78–85. 10.1016/j.clim.2009.05.014
46 Aytekin C, Tuygun N, Gokce S, Dogu F, Ikinciogullari A. Selective IgA deficiency: Clinical and laboratory features of 118 children in Turkey. J Clin Immunol. 2012;32:961–6. 10.1007/s10875-012-9702-3
47 Moschese V, Chini L, Graziani S, Sgrulletti M, Gallo V, Di Matteo G, et al. Follow-up and outcome of symptomatic partial or absolute IgA deficiency in children. Eur J Pediatr. 2019;178(1):51–60. 10.1007/s00431-018-3248-1
48 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;133:101–6. 10.1007/BF00441577
49 Živković J, Lipej M, Banić I, Bulat Lokas S, Nogalo B, Lulić Jurjević R, et al. Respiratory and allergic disorders in children with severe and partial immunoglobulin A immunodeficiency. Scand J Immunol. 2019;90:e12828. 10.1111/sji.12828
50 Gualdi G, Lougaris V, Baronio M, Vitali M, Tampella G, Moratto D, et al. Burden of skin disease in selective IgA deficiency and common variable immunodeficiency. J Investig Allergol Clin Immunol. 2015;25(5):369–71.
51 Papadopoulou A, Mermiri D, Taousani S, Triga M, Nicolaidou P, Priftis KN. Bronchial hyper-responsiveness in selective IgA deficiency. Pediatr Allergy Immunol. 2005;16:495–500. 10.1111/j.1399-3038.2005.00316.x
52 Abolhassani H, Gharib B, Shahinpour S, Masoom SN, Havaei A, Mirminachi B, et al. Autoimmunity in patients with selective IgA deficiency. J Investig Allergol Clin Immunol. 2015;25:112–9.
53 Shkalim V, Monselize Y, Segal N, Zan-Bar I, Hoffer V, Garty BZ. Selective IgA deficiency in children in Israel. J Clin Immunol. 2010;30:761–5. 10.1007/s10875-010-9438-x
54 Plebani A, Monafo V, Ugazio AG, Monti C, Avanzini MA, Massimi P, et al. Comparison of the frequency of atopic diseases in children with severe and partial IgA deficiency. Int Arch Allergy Immunol. 1987;82:485–6. 10.1159/000234261
55 Wang W, Yao T, Zhang T, Quan M, Wang C, Zhang L, et al. Selective immunoglobulin A deficiency (SIgAD) primarily leads to recurrent infections and autoimmune diseases: A retrospective study of Chinese patients in the past 40 years. Genes Dis. 2020;7:115–21. 10.1016/j.gendis.2019.10.014
56 De Laat PC, Weemaes CM, Gonera R, Van Munster PJ, Bakkeren JA, Stoelinga GB. Clinical manifestations in selective IgA deficiency in childhood. A follow-up report. Acta Paediatr. 1991;80:798–804. 10.1111/j.1651-2227.1991.tb11952.x
57 Sandin A, Björkstén B, Böttcher MF, Englund E, Jenmalm MC, Bråbäck L. High salivary secretory IgA antibody levels are associated with less late-onset wheezing in IgE-sensitized infants. Pediatr Allergy Immunol. 2011;22:477–81. 10.1111/j.1399-3038.2010.01106.x
58 Aksu KAM, Asilsoy S et al. Approach to diagnosis and treatment of atopic dermatitis: National Guide 2018. Asthma Allergy Immunol. 2018;16(2):1–95. 10.4274/turkderm.87143
59 Serbes M, Özkan B, Can D, Meşe T, et al. Skin allergies. Izmir Behçet Uz Children’s Hospital Pediatrics, Ankara: Nobel Medicine Bookstores; 2022. pp. 514–23.
60 Strait RT, Mahler A, Hogan S, Khodoun M, Shibuya A, Finkelman FD. Ingested allergens must be absorbed systemically to induce systemic anaphylaxis. J Allergy Clin Immunol. 2011;127:982–989.e1. 10.1016/j.jaci.2011.01.034
61 Szczawińska-Popłonyk A, Bręborowicz A, Ossowska L. Food allergy in children with hypogammaglobulinemia. Pediatr Pol. 2012;87:444–8. 10.1016/j.pepo.2012.07.004
62 Heeb LEM, Egholm C, Boyman O. Evolution and function of interleukin-4 receptor signaling in adaptive immunity and neutrophils. Genes Immun. 2020;21:143–9. 10.1038/s41435-020-0095-7
63 Patel DF, Peiró T, Bruno N, Vuononvirta J, Akthar S, Puttur F, et al. Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation. Sci Immunol. 2019;4(41):eaax7006. 10.1126/sciimmunol.aax7006
64 Woytschak J, Keller N, Krieg C, Impellizzieri D, Thompson RW, Wynn TA, et al. Type 2 interleukin-4 receptor signaling in neutrophils antagonizes their expansion and migration during infection and inflammation. Immunity. 2016;45:172–84. 10.1016/j.immuni.2016.06.025
65 Brandtzaeg P, Nilssen DE. Mucosal aspects of primary B-cell deficiency and gastrointestinal infections. Curr Opin Gastroenterol. 1995;11:532–40. 10.1111/j.1749-6632.2002.tb04131.x
66 Brandtzaeg P, Karlsson G, Hansson G, Petruson B, Björkander J, Hanson L. The clinical condition of IgA-deficient patients is related to the proportion of IgD-and IgM-producing cells in their nasal mucosa. Clin Exp Immunol. 1987;67(3):626.
67 Kanok JM, Steinberg P, Cassidy JT, Petty RE, Bayne NK. Serum IgE levels in patients with selective IgA deficiency. Ann Allergy. 1978;41:22–3.
68 Burks AW, Sampson HA, Buckley RH. Anaphylactic reactions after gamma globulin administration in patients with hypogammaglobulinemia. N Engl J Med. 1986;314:560–4. 10.1056/NEJM198602273140907
69 Pearce N, Aït-Khaled N, Beasley R, Mallol J, Keil U, Mitchell E, et al. Worldwide trends in the prevalence of asthma symptoms: Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2007;62(9):758–66. 10.1136/thx.2006.070169
70 Akçay A, Tamay Z, Hocaoğlu AB, Ergin A, Güler N. Risk factors affecting asthma prevalence in adolescents living in Istanbul, Turkey. Allergol Immunopathol (Madr). 2014;42(5):449–58. 10.1016/j.aller.2013.05.005
71 Rebelo Gomes E, Fonseca J, Araujo L, Demoly P. Drug allergy claims in children: From self-reporting to confirmed diagnosis. Clin Exp Allergy. 2008;38(1):191–8. 10.1111/j.1365-2222.2007.02870.x
72 Erkoçoğlu M, Kaya A, Civelek E, Ozcan C, Cakır B, Akan A, et al. Prevalence of confirmed immediate type drug hypersensitivity reactions among school children. Pediatr Allergy Immunol. 2013;24(2):160–7. 10.1111/pai.12047
73 Meerwaldt R, Odink RJ, Landaeta R, Aarts F, Brunekreef B, Gerritsen J, et al. A lower prevalence of atopy symptoms in children with type 1 diabetes mellitus. Clin Exp Allergy. 2002;32(2).254–5. 10.1046/j.13652222.2002.01311.x
74 Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136:1186–1205.e78. 10.1016/j.jaci.2015.04.049