{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:18:07Z","timestamp":1788257887624,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2021\/43\/O\/NZ5\/00480"],"award-info":[{"award-number":["2021\/43\/O\/NZ5\/00480"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2021\/43\/O\/NZ5\/00480"],"award-info":[{"award-number":["2021\/43\/O\/NZ5\/00480"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Asthma is a heterogeneous disease that often begins in childhood and frequently occurs alongside allergic conditions. In asthma research, it is important to focus on proteins that are the primary regulators of cellular physiology. The differences in the proteome between children with asthma and those with an atopic background remain poorly understood. The present study included 130 serum samples from four groups of pediatric patients under the age of five: (1) with asthma and IgE-dependent allergies; (2) with non-atopic asthma; (3) non-asthmatics with IgE-dependent allergy; and (4) a control group without asthma and IgE-dependent allergies. The serum samples were used for protein\u2013peptide profiling and proteomic identification using nanoLC-MALDI-TOF\/TOF MS\/MS. The obtained data were analyzed using univariate statistics and the STRING tool v12.0 to identify protein\u2013protein potential interactions. A total of seven proteins were identified as discriminative between the study groups: A2M, AACT, IgG3, C3, ITIH2, IgG3 and IGK. All of them were upregulated in patients with IgE-dependent allergy compared to other study groups. STRING analysis identified functional associations among four proteins (AACT, A2M, C3, and ITIH2) with discriminatory potential for distinguishing between non-atopic asthma and non-asthmatic patients with IgE-dependent allergy. The results suggest that the identified putative protein markers overlap in cellular pathways, including those associated with the pathophysiology of asthma and allergic disorders. These findings provide further insight into the overall proteomic profile of pediatric patients with asthma and IgE-dependent allergy, highlighting its heterogeneity across the analyzed groups.<\/jats:p>","DOI":"10.3390\/ijms27177769","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Profile Differences in Immune-Related Diseases in Pediatric Patients Under Five Years Old: Asthma and IgE-Dependent Allergies\u2014A Pilot Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9880-0740","authenticated-orcid":false,"given":"Natalia","family":"Rzetecka-Ma\u0144ka","sequence":"first","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, 60-812 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2475-1066","authenticated-orcid":false,"given":"Joanna","family":"Matysiak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, University of Kalisz, 62-800 Kalisz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-2603","authenticated-orcid":false,"given":"Eliza","family":"Matuszewska-Mach","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Paulina","family":"Sobkowiak","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Pediatric Allergy and Clinical Immunology, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6724-1499","authenticated-orcid":false,"given":"Irena","family":"Wojsyk-Banaszak","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Pediatric Allergy and Clinical Immunology, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Anna","family":"Br\u0119borowicz","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Pediatric Allergy and Clinical Immunology, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4025-5614","authenticated-orcid":false,"given":"Paulina","family":"Borysewicz","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, 60-812 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5028-1408","authenticated-orcid":false,"given":"Agnieszka","family":"Klupczy\u0144ska-Gabryszak","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9993-1504","authenticated-orcid":false,"given":"Jan","family":"Matysiak","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhou, W., and Tang, J. (2025). Prevalence and Risk Factors for Childhood Asthma: A Systematic Review and Meta-Analysis. BMC Pediatr., 25.","DOI":"10.1186\/s12887-025-05409-x"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1136\/thoraxjnl-2020-214655","article-title":"Asthma and All-Cause Mortality in Children and Young Adults: A Population-Based Study","volume":"75","author":"Bower","year":"2020","journal-title":"Thorax"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e13784","DOI":"10.1111\/pai.13784","article-title":"The Influence of Urban Exposures and Residence on Childhood Asthma","volume":"33","author":"Grant","year":"2022","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_4","unstructured":"(2026, January 26). Global Initiative for Asthma. Available online: https:\/\/ginasthma.org\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s11882-025-01198-6","article-title":"Metabolomics in Childhood Asthma\u2014A Promising Tool to Meet Various Clinical Needs","volume":"25","author":"Rzetecka","year":"2025","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104936","DOI":"10.1016\/j.ebiom.2023.104936","article-title":"Proteomic Signatures of Eosinophilic and Neutrophilic Asthma from Serum and Sputum","volume":"99","author":"Asamoah","year":"2024","journal-title":"eBioMedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.21037\/jtd-23-974","article-title":"Serum Proteomics Identifies Novel Diagnostic Biomarkers for Asthma in Preschool Children","volume":"16","author":"Ding","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e12357","DOI":"10.1002\/clt2.12357","article-title":"Proteomic Analysis Reveals Potential Therapeutic Targets for Childhood Asthma through Mendelian Randomization","volume":"14","author":"Wu","year":"2024","journal-title":"Clin. Transl. Allergy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"D730","DOI":"10.1093\/nar\/gkae1113","article-title":"The STRING Database in 2025: Protein Networks with Directionality of Regulation","volume":"53","author":"Szklarczyk","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12948-018-0102-y","article-title":"Markers of Atopic Dermatitis, Allergic Rhinitis and Bronchial Asthma in Pediatric Patients: Correlation with Filaggrin, Eosinophil Major Basic Protein and Immunoglobulin E","volume":"16","author":"Rasheed","year":"2018","journal-title":"Clin. Mol. Allergy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1586\/eci.09.84","article-title":"A Complex Role for Complement in Allergic Asthma","volume":"6","author":"Zhang","year":"2010","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/jth.15647","article-title":"Alpha-2-Macroglobulin in Hemostasis and Thrombosis: An Underestimated Old Double-Edged Sword","volume":"20","author":"Lagrange","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/neuonc\/noaa264","article-title":"Alpha 1-Antichymotrypsin Contributes to Stem Cell Characteristics and Enhances Tumorigenicity of Glioblastoma","volume":"23","author":"Zarco","year":"2021","journal-title":"Neuro-Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e24622","DOI":"10.1002\/jcla.24622","article-title":"Urine Inter-Alpha-Trypsin Inhibitor Family-Related Proteins May Serve as Biomarkers for Disease Activity of Lupus","volume":"36","author":"Jiang","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, X., Guo, L., Bai, Y., Tian, Y., and Luo, H. (2024). The Function of the Inter-Alpha-Trypsin Inhibitors in the Development of Disease. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1432224"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1600-065X.2011.01064.x","article-title":"The Signaling Networks of the Herpesvirus Entry Mediator (TNFRSF14) in Immune Regulation","volume":"244","author":"Steinberg","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1189\/jlb.0910528","article-title":"Regulation of Inflammation, Autoimmunity, and Infection Immunity by HVEM-BTLA Signaling","volume":"89","author":"Shui","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2000645","DOI":"10.1183\/13993003.00645-2020","article-title":"Complement C3 and Allergic Asthma: A Cohort Study of the General Population","volume":"57","author":"Rasmussen","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s12098-010-0117-y","article-title":"Complement Components (C3, C4) as Inflammatory Markers in Asthma","volume":"77","author":"Fattah","year":"2010","journal-title":"Indian J. Pediatr."},{"key":"ref_20","first-page":"525","article-title":"Elevated Complement C3a in Plasma from Patients with Severe Acute Asthma","volume":"112","author":"Nakano","year":"2003","journal-title":"Respir. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"683","DOI":"10.2147\/COPD.S407491","article-title":"A2M Serves as Promising Biomarker for Chronic Obstructive Pulmonary Disease","volume":"18","author":"Xiao","year":"2023","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"110249","DOI":"10.1016\/j.intimp.2023.110249","article-title":"Quantitative Proteomics Profiling of Plasma from Children with Asthma","volume":"119","author":"Zhou","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hollander, C., Westin, U., Wallmark, A., Piitulainen, E., Sveger, T., and Janciauskiene, S.M. (2007). Plasma Levels of Alpha1-Antichymotrypsin and Secretory Leukocyte Proteinase Inhibitor in Healthy and Chronic Obstructive Pulmonary Disease (COPD) Subjects with and without Severe A1-Antitrypsin Deficiency. BMC Pulm. Med., 7.","DOI":"10.1186\/1471-2466-7-1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1080\/02770903.2020.1729382","article-title":"Expression of Herpesvirus Entry Mediator Gene as a Potential Biomarker for Disease Severity in Patients with Persistent Asthma","volume":"58","author":"Xiong","year":"2021","journal-title":"J. Asthma"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Anderluh, G., and Gilbert, R. (2014). Evolution of the Complement System. MACPF\/CDC Proteins\u2014Agents of Defence, Attack and Invasion, Springer.","DOI":"10.1007\/978-94-017-8881-6"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"945","DOI":"10.3892\/ijo.2016.3330","article-title":"Identification of Haptoglobin Peptide as a Novel Serum Biomarker for Lung Squamous Cell Carcinoma by Serum Proteome and Peptidome Profiling","volume":"48","author":"Okano","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e06554","DOI":"10.1016\/j.heliyon.2021.e06554","article-title":"Serum Complement C3 and A2-Macroglobulin Are Potentially Useful Biomarkers for Inflammatory Bowel Disease Patients","volume":"7","author":"Okada","year":"2021","journal-title":"Heliyon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12935-022-02572-4","article-title":"Alpha-1-Antichymotrypsin as a Novel Biomarker for Diagnosis, Prognosis, and Therapy Prediction in Human Diseases","volume":"22","author":"Jin","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/BF02734145","article-title":"Complement Components (C3, C4) in Childhood Asthma","volume":"72","author":"Najam","year":"2005","journal-title":"Indian J. Pediatr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1007\/s10038-008-0304-0","article-title":"Association Study of the C3 Gene with Adult and Childhood Asthma","volume":"53","author":"Inoue","year":"2008","journal-title":"J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102253","DOI":"10.1016\/j.omtn.2024.102253","article-title":"Unbiased Plasma Profiling Using Pre-Selected RNA Aptamer Pools Predicts Mortality in COVID-19 and Identifies Protein Risk Factors","volume":"35","author":"Dupont","year":"2024","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2200070","DOI":"10.1002\/prca.202200070","article-title":"Plasma Proteomics Identify Potential Severity Biomarkers from COVID-19 Associated Network","volume":"17","author":"Sahin","year":"2022","journal-title":"Proteom. Clin. Appl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pccm.2024.02.002","article-title":"Omics Approaches in Asthma Research: Challenges and Opportunities","volume":"2","author":"Yue","year":"2024","journal-title":"Chin. Med. J. Pulm. Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Alashkar Alhamwe, B., Potaczek, D.P., Miethe, S., Alhamdan, F., Hintz, L., Magomedov, A., and Garn, H. (2021). Extracellular Vesicles and Asthma\u2014More Than Just a Co-Existence. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094984"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Grueso-Navarro, E., Navarro, P., Laserna-Mendieta, E.J., Lucendo, A.J., and Arias-Gonz\u00e1lez, L. (2023). Blood-Based Biomarkers for Eosinophilic Esophagitis and Concomitant Atopic Diseases: A Look into the Potential of Extracellular Vesicles. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043669"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e222819","DOI":"10.1136\/thorax-2024-222819","article-title":"Association between Asthma and Type 2 Diabetes in a Swedish Adult Population: A Register-Based Cross-Sectional Study","volume":"80","author":"Mubanga","year":"2025","journal-title":"Thorax"},{"key":"ref_37","first-page":"e36047","article-title":"Type 2 Diabetes Mellitus and Asthma: Pathomechanisms of Their Association and Clinical Implications","volume":"15","author":"Uppal","year":"2023","journal-title":"Cureus"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e700","DOI":"10.20883\/medical.e700","article-title":"Publication Ethics of Human Studies in the Light of the Declaration of Helsinki\u2014A Mini-Review","volume":"91","author":"Guzik","year":"2022","journal-title":"J. Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1167\/iovs.67.3.23","article-title":"Common and Distinct Features in Serum Proteomic Profiles in Keratoconus, Post-Laser Vision Correction Ectasia, and Pellucid Marginal Degeneration","volume":"67","author":"Wysocka","year":"2026","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Matuszewska, E., Matysiak, J., Rosi\u0144ski, G., K\u0119dzia, E., Z\u0105bek, W., Zawadzi\u0144ski, J., and Matysiak, J. (2021). Mining the Royal Jelly Proteins: Combinatorial Hexapeptide Ligand Library Significantly Improves the MS-Based Proteomic Identification in Complex Biological Samples. Molecules, 26.","DOI":"10.3390\/molecules26092762"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING Database in 2023: Protein-Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7769\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:55:27Z","timestamp":1788256527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,30]]},"references-count":41,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177769"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177769","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,30]]}}}