Table Info

Table 2.

Basic characteristics and demographics of the children in the study

Characteristics	Patients with confirmed immune deficiency (n = 45)	Patients without confirmed immune deficiency (n = 340)	P value
Gender (male:female)	25:20	189:151	P = 0.84^*
Age (years) ± SD	5.10 ± 3.88	5.73 ± 3.75	P = 0.16^#
Comorbidity (none):atopy:autoimmunity:autoimmunity and atopy	19:16:6:4	182:129:18:11	P = 0.023^*
Infection confirmed yes:no	21:24	143:197	P = 0.34^*
IgE (kU/L) ± SD	786.79 ± 3,035.86	248.90 ± 1,400.38	P = 0.01^#
Elevated IgE (n, %)	16, 35.55%	76, 20.54%	P = 0.05^*

^* Chi-square; ^# analysis of variance (ANOVA). SD: standard deviation

Declarations

Author contributions

PK: Conceptualization, Validation, Investigation, Resources, Data curation, Writing—original draft, Visualization. VP: Validation, Investigation. MS: Validation, Resources, Visualization. GP: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing—review & editing, Visualization, Supervision. All authors have read and agreed to the published version of the manuscript.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

The datasets for this manuscript are not publicly available but can be requested from the corresponding author (Polina Kostova, poli.mu@gmail.com).

Funding

Not applicable.

Copyright

References

Spolidoro GCI, Amera YT, Ali MM, Nyassi S, Lisik D, Ioannidou A, et al. Frequency of food allergy in Europe: an updated systematic review and meta-analysis. Allergy. 2023;78:351–68. [DOI] [PubMed] [PMC]

Shoda T, Futamura M, Yang L, Yamamoto-Hanada K, Narita M, Saito H, et al. Timing of eczema onset and risk of food allergy at 3 years of age: a hospital-based prospective birth cohort study. J Dermatol Sci. 2016;84:144–8. [DOI] [PubMed]

Xing Y, Wong GW. Environmental influences and allergic diseases in the Asia-Pacific region: What will happen in next 30 years? Allergy Asthma Immunol Res. 2022;14:21–39. [DOI] [PubMed] [PMC]

Lack G. Early exposure hypothesis: Where are we now? Clin Transl Allergy. 2011;1:S71. [DOI]

Lee-Sarwar KA, Chen YC, Lasky-Su J, Kelly RS, Zeiger RS, O’Connor GT, et al. Early-life fecal metabolomics of food allergy. Allergy. 2023;78:512–21. [DOI] [PubMed] [PMC]

Venter C, Meyer RW, Greenhawt M, Pali-Schöll I, Nwaru B, Roduit C, et al. Role of dietary fiber in promoting immune health—an EAACI position paper. Allergy. 2022;77:3185–98. [DOI] [PubMed]

Bermudez-Brito M, Sahasrabudhe NM, Rösch C, Schols HA, Faas MM, de Vos P. The impact of dietary fibers on dendritic cell responses in vitro is dependent on the differential effects of the fibers on intestinal epithelial cells. Mol Nutr Food Res. 2015;59:698–710. [DOI] [PubMed]

Podlecka D, Jerzyńska J, Sanad K, Polańska K, Bobrowska-Korzeniowska M, Stelmach I, et al. Micronutrients and the risk of allergic diseases in school children. Int J Environ Res Public Health. 2022;19:12187. [DOI] [PubMed] [PMC]

Peroni DG, Hufnagl K, Comberiati P, Roth-Walter F. Lack of iron, zinc, and vitamins as a contributor to the etiology of atopic diseases. Front Nutr. 2023;9:1032481. [DOI] [PubMed] [PMC]

10.

Roth-Walter F. Iron-deficiency in atopic diseases: innate immune priming by allergens and siderophores. Front Allergy. 2022;3:859922. [DOI] [PubMed] [PMC]

11.

Vlieg-Boerstra B, Groetch M, Vassilopoulou E, Meyer R, Laitinen K, Swain A, et al. The immune-supportive diet in allergy management: a narrative review and proposal. Allergy. 2023;78:1441–58. [DOI] [PubMed]

12.

Su KW, Cetinbas M, Martin VM, Virkud YV, Seay H, Ndahayo R, et al. Early infancy dysbiosis in food protein-induced enterocolitis syndrome: a prospective cohort study. Allergy. 2023;78:1595–604. [DOI] [PubMed] [PMC]

13.

Notarangelo LD, Bacchetta R, Casanova JL, Su HC. Human inborn errors of immunity: an expanding universe. Sci Immunol. 2020;5:eabb1662. [DOI] [PubMed] [PMC]

14.

Vaseghi-Shanjani M, Smith KL, Sara RJ, Modi BP, Branch A, Sharma M, et al. Inborn errors of immunity manifesting as atopic disorders. J Allergy Clin Immunol. 2021;148:1130–9. [DOI] [PubMed]

15.

Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Mol Med. 2011;17:1383–96. [DOI] [PubMed] [PMC]

16.

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. [DOI] [PubMed]

17.

Lawrence MG, Palacios-Kibler TV, Workman LJ, Schuyler AJ, Steinke JW, Payne SC, et al. Low serum IgE is a sensitive and specific marker for common variable immunodeficiency (CVID). J Clin Immunol. 2018;38:225–33. [DOI] [PubMed] [PMC]

18.

Urschel S, Kayikci L, Wintergerst U, Notheis G, Jansson A, Belohradsky BH. Common variable immunodeficiency disorders in children: delayed diagnosis despite typical clinical presentation. J Pediatr. 2009;154:888–94. [DOI] [PubMed]

19.

Ogershok PR, Hogan MB, Welch JE, Corder WT, Wilson NW. Spectrum of illness in pediatric common variable immunodeficiency. Ann Allergy Asthma Immunol. 2006;97:653–6. [DOI] [PubMed]

20.

Yong PL, Orange JS, Sullivan KE. Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells. Pediatr Allergy Immunol. 2010;21:852–8. [DOI] [PubMed]

21.

Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, et al. JM2, encoding a fork head–related protein, is mutated in X-linked autoimmunity–allergic disregulation syndrome. J Clin Invest. 2000;106:R75–81. [DOI] [PubMed] [PMC]

22.

Torgerson TR, Linane A, Moes N, Anover S, Mateo V, Rieux-Laucat F, et al. Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 gene. Gastroenterology. 2007;132:1705–17. [DOI] [PubMed]

23.

Siegel AM, Stone KD, Cruse G, Lawrence MG, Olivera A, Jung MY, et al. Diminished allergic disease in patients with STAT3 mutations reveals a role for STAT3 signaling in mast cell degranulation. J Allergy Clin Immunol. 2013;132:1388–96. Erratum in: J Allergy Clin Immunol. 2014;133:1232. [DOI] [PubMed] [PMC]

24.

de Wit J, van Wijck RTA, Dalm VASH, Snyder KL, Totté JEE, Pasmans SGMA, et al.; Academic Center of Excellence (ACE) workgroups Allergic Diseases and Rare Immunological Disease Centre (RIDC). Molecular clustering of genes related to the atopic syndrome: towards a more tailored approach and personalized medicine? Clin Transl Allergy. 2019;9:34. [DOI] [PubMed] [PMC]

25.

Ponsford MJ, Klocperk A, Pulvirenti F, Dalm VASH, Milota T, Cinetto F, et al. Hyper-IgE in the allergy clinic––when is it primary immunodeficiency? Allergy. 2018;73:2122–36. [DOI] [PubMed]

26.

Castagnoli R, Lougaris V, Giardino G, Volpi S, Leonardi L, La Torre F, et al.; Immunology Task Force of the Italian Society of Pediatric Allergy and Immunology (SIAIP). Inborn errors of immunity with atopic phenotypes: a practical guide for allergists. World Allergy Organ J. 2021;14:100513. [DOI] [PubMed] [PMC]

27.

Sicherer SH, Furlong TJ, Maes HH, Desnick RJ, Sampson HA, Gelb BD. Genetics of peanut allergy: a twin study. J Allergy Clin Immunol. 2000;106:53–6. [DOI] [PubMed]

28.

Goleva E, Calatroni A, LeBeau P, Berdyshev E, Taylor P, Kreimer S, et al. Skin tape proteomics identifies pathways associated with transepidermal water loss and allergen polysensitization in atopic dermatitis. J Allergy Clin Immunol. 2020;146:1367–78. [DOI] [PubMed] [PMC]

29.

Milner JD. Primary atopic disorders. Annu Rev Immunol. 2020;38:785–808. [DOI] [PubMed]

30.

Vaseghi-Shanjani M, Snow AL, Margolis DJ, Latrous M, Milner JD, Turvey SE, et al. Atopy as immune dysregulation: offender genes and targets. J Allergy Clin Immunol Pract. 2022;10:1737–56. [DOI] [PubMed]

31.

Sharma M, Leung D, Momenilandi M, Jones LCW, Pacillo L, James AE, et al. Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease. J Exp Med. 2023;220:e20221755. [DOI] [PubMed] [PMC]

32.

Takeuchi I, Yanagi K, Takada S, Uchiyama T, Igarashi A, Motomura K, et al. STAT6 gain-of-function variant exacerbates multiple allergic symptoms. J Allergy Clin Immunol. 2023;151:1402–9.e6. [DOI] [PubMed]

33.

Suratannon N, Ittiwut C, Dik WA, Ittiwut R, Meesilpavikkai K, Israsena N, et al. A germline STAT6 gain-of-function variant is associated with early-onset allergies. J Allergy Clin Immunol. 2023;151:565–71.e9. [DOI] [PubMed]

34.

Baris S, Benamar M, Chen Q, Catak MC, Martínez-Blanco M, Wang M, et al. Severe allergic dysregulation due to a gain of function mutation in the transcription factor STAT6. J Allergy Clin Immunol. 2023;152:182–94.e7. [DOI] [PubMed]

35.

Kostova P, Papochieva V, Miteva D, Georgieva B, Mileva S, Shahid M, et al. Elevated IgE levels—an allergy or an underlying inborn error of immunity in children with recurrent infections? Antibodies (Basel). 2023;12:70. [DOI] [PubMed] [PMC]

36.

Ghaini M, Jamee M, Mahdaviani SA, Mesdaghi M, Eskandarzadeh S, Rae W, et al. The prevalence of atopic manifestations in 313 Iranian patients with inborn errors of immunity. Int Arch Allergy Immunol. 2021;182:1122–6. [DOI] [PubMed]

37.

El-Sayed ZA, El-Ghoneimy DH, Ortega-Martell JA, Radwan N, Aldave JC, Al-Herz W, et al. Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: a worldwide study. World Allergy Organ J. 2022;15:100657. [DOI] [PubMed] [PMC]