Predictors of relapse rate in pediatric allergy patients with primary immunodeficiency
DOI:
https://doi.org/10.5281/zenodo.22812530Keywords:
primary immunodeficiency, pediatric allergy, relapse, common variable immunodeficiency, immunoglobulin replacementAbstract
Background: Children with primary immunodeficiency (PID) carry a disproportionate burden of allergic disease, and in this population relapse of respiratory or atopic symptoms is difficult to separate from breakthrough infection driven by the same antibody defect [1,2].
Objective: This review synthesizes published evidence on predictors of relapse in pediatric allergy patients with PID, organized around immunological phenotype, allergic biomarker status, and treatment adequacy.
Methods: We reviewed cohort studies, registry analyses, and consensus practice parameters addressing relapse or exacerbation in patients with a documented antibody deficiency and an allergic phenotype, supplemented by pediatric asthma risk-index literature applied to this population [16,19].
Findings: The most consistent predictors are reduced switched memory B cells and low baseline IgG [9,10], comorbid atopic disease with elevated IgE or eosinophilia [1,21], and inadequate immunoglobulin trough level or delayed diagnosis [17,18,28].
Conclusions: Relapse risk in this population is best predicted by combining immunological phenotyping, structured allergy assessment, and individualized immunoglobulin trough monitoring; pediatric-specific prospective cohorts are still needed to validate these largely adult-derived predictors in children [11,27].
References
Agondi, R.C., Barros, M.T., Rizzo, L.V., Kalil, J., Giavina-Bianchi, P. (2010) Allergic asthma in patients with common variable immunodeficiency. Allergy, 65(4): 510-515. DOI: 10.1111/j.1398-9995.2009.02211.x
Urm, S.H., Yun, H.D., Fenta, Y.A., et al. (2013) Asthma and risk of selective IgA deficiency or common variable immunodeficiency: a population-based case-control study. Mayo Clinic Proceedings, 88(8): 813-821. DOI: 10.1016/j.mayocp.2013.05.021
Tangye, S.G., Al-Herz, W., Bousfiha, A., et al. (2022) Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. Journal of Clinical Immunology, 42(7): 1473-1507. DOI: 10.1007/s10875-022-01289-3
Bousfiha, A., Jeddane, L., Picard, C., et al. (2022) The 2022 Update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity. Journal of Clinical Immunology, 42(7): 1508-1520. DOI: 10.1007/s10875-022-01352-z
Yel, L. (2010) Selective IgA deficiency. Journal of Clinical Immunology, 30(1): 10-16. DOI: 10.1007/s10875-009-9357-x
Boyle, J.M., Buckley, R.H. (2007) Population prevalence of diagnosed primary immunodeficiency diseases in the United States. Journal of Clinical Immunology, 27(5): 497-502. DOI: 10.1007/s10875-007-9103-1
Modell, V., Orange, J.S., Quinn, J., Modell, F. (2018) Global report on primary immunodeficiencies: 2018 update. Immunologic Research, 66(3): 367-380. DOI: 10.1007/s12026-018-8996-5
Chapel, H., Lucas, M., Lee, M., et al. (2008) Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood, 112(2): 277-286. DOI: 10.1182/blood-2007-11-124545
Wehr, C., Kivioja, T., Schmitt, C., et al. (2008) The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood, 111(1): 77-85. DOI:
1182/blood-2007-06-091744 10. Resnick, E.S., Moshier, E.L., Godbold, J.H., Cunningham-Rundles, C. (2012) Morbidity and mortality in common variable immune deficiency over 4 decades. Blood, 119(7): 1650-1657. DOI: 10.1182/blood-2011-09-377945
Gathmann, B., Mahlaoui, N., Gerard, L., et al. (2014) Clinical picture and treatment of 2212 patients with common variable immunodeficiency. Journal of Allergy and Clinical Immunology, 134(1): 116-126. DOI: 10.1016/j.jaci.2013.12.1077
Cunningham-Rundles, C., Bodian, C. (1999) Common variable immunodeficiency: clinical and immunological features of 248 patients. Clinical Immunology, 92(1): 34-48. DOI: 10.1006/clim.1999.4725
Notarangelo, L.D. (2010) Primary immunodeficiencies. Journal of Allergy and Clinical Immunology, 125(2 Suppl 2): S182-S194. DOI: 10.1016/j.jaci.2009.07.053
Picard, C., Bobby Gaspar, H., Al-Herz, W., et al. (2018) International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. Journal of Clinical Immunology, 38(1): 96-128. DOI: 10.1007/s10875-017-0464-9
Yong, P.F., Thaventhiran, J.E., Grimbacher, B. (2011) "A rose is a rose is a rose," but CVID is Not CVID: common variable immune deficiency (CVID), what do we know in 2011? Advances in Immunology, 111: 47-107. DOI: 10.1016/B978-0-12-385991-4.00002-7
Bonilla, F.A., Khan, D.A., Ballas, Z.K., et al. (2015) Practice parameter for the diagnosis and management of primary immunodeficiency. Journal of Allergy and Clinical Immunology, 136(5): 1186-1205. DOI: 10.1016/j.jaci.2015.04.049
Orange, J.S., Hossny, E.M., Weiler, C.R., et al. (2006) 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. Journal of Allergy and Clinical Immunology, 117(4 Suppl): S525-S553. DOI: 10.1016/j.jaci.2006.01.015
Perez, E.E., Orange, J.S., Bonilla, F., et al. (2017) Update on the use of immunoglobulin in human disease: a review of evidence. Journal of Allergy and Clinical Immunology, 139(3S): S1-S46. DOI: 10.1016/j.jaci.2016.09.023
Castro-Rodriguez, J.A., Holberg, C.J., Wright, A.L., Martinez, F.D. (2000) A clinical index to define risk of asthma in young children with recurrent wheezing. American Journal of Respiratory and Critical Care Medicine, 162(4 Pt 1): 1403-1406. DOI: 10.1164/ajrccm.162.4.9912111
Guilbert, T.W., Morgan, W.J., Zeiger, R.S., et al. (2006) Long-term inhaled corticosteroids in preschool children at high risk for asthma. New England Journal of Medicine, 354(19): 1985-1997. DOI: 10.1056/NEJMoa051378
Aghamohammadi, A., Cheraghi, T., Gharagozlou, M., et al. (2009) IgA deficiency: correlation between clinical and immunological phenotypes. Journal of Clinical Immunology, 29(1): 130-136. DOI: 10.1007/s10875-008-9229-9
Barlan, I.B., Geha, R.S., Schneider, L.C. (1993) Therapy for patients with recurrent infections and low serum IgG3. Journal of Allergy and Clinical Immunology, 92(2): 353-355. DOI: 10.1016/0091-6749(93)90178-D
Bacharier, L.B., Boner, A., Carlsen, K.H., et al. (2008) Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy, 63(1): 5-34. DOI: 10.1111/j.1398-9995.2007.01586.x
Agarwal, S., Cunningham-Rundles, C. (2009) Autoimmunity in common variable immunodeficiency. Current Allergy and Asthma Reports, 9(5): 347-352. DOI: 10.1007/s11882-009-0051-0
Cunningham-Rundles, C. (2010) How I treat common variable immune deficiency. Blood, 116(1): 7-15. DOI: 10.1182/blood-2010-01-254417
Ameratunga, R., Woon, S.T., Gillis, D., Koopmans, W., Steele, R. (2013) New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clinical and Experimental Immunology, 174(2): 203-211. DOI: 10.1111/cei.12178
Duraisingham, S.S., Buckland, M., Dempster, J., Lorenzo, L., Grigoriadou, S., Longhurst, H.J. (2014) Primary vs. secondary antibody deficiency: clinical features and infection outcomes of immunoglobulin replacement. PLoS ONE, 9(6): e100324. DOI: 10.1371/journal.pone.0100324
de Vries, E. (2012) Patient-centred screening for primary immunodeficiency, a multi-stage diagnostic protocol designed for non-immunologists. Clinical and Experimental Immunology, 167(1): 108-119. DOI: 10.1111/j.1365-2249.2011.04461.x
Fried, A.J., Bonilla, F.A. (2009) Pathogenesis, diagnosis, and management of primary antibody deficiencies and infections. Clinical Microbiology Reviews, 22(3): 396-414. DOI: 10.1128/CMR.00001-09
Wood, P., Stanworth, S., Burton, J., et al. (2007) Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clinical and Experimental Immunology, 149(3): 410-423. DOI: 10.1111/j.1365-2249.2007.03432.x
Quinti, I., Soresina, A., Spadaro, G., et al. (2007) Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. Journal of Clinical Immunology, 27(3): 308-316. DOI: 10.1007/s10875-007-9075-1
Oksenhendler, E., Gerard, L., Fieschi, C., et al. (2008) Infections in 252 patients with common variable immunodeficiency. Clinical Infectious Diseases, 46(10): 1547-1554. DOI: 10.1086/587669
Locke, B.A., Dasu, T., Verbsky, J.W. (2014) Laboratory diagnosis of primary immunodeficiencies. Clinical Reviews in Allergy and Immunology, 46(2): 154-168. DOI: 10.1007/s12016-014-8412-4
Ballow, M. (2002) Primary immunodeficiency disorders: antibody deficiency. Journal of Allergy and Clinical Immunology, 109(4): 581-591. DOI: 10.1067/mai.2002.122466
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Paula Gomez, et al.
This work is licensed under a Creative Commons Attribution 4.0 International License.
