{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:09:05Z","timestamp":1784632145588,"version":"3.55.0"},"reference-count":83,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As the predominant antibody isotype at human mucosal surfaces, immunoglobulin A (IgA) exerts critical functions in mucosal defense and systemic immune homeostasis. The two IgA subclasses, IgA1 and IgA2, possess distinct structural and functional features and assemble into dimeric IgA (dIgA) and secretory IgA (sIgA) under physiological conditions. With advances in cryo-electron microscopy, the molecular architecture and assembly of sIgA have been clearly characterized. While IgA protects hosts from pathogenic infection and sustains immune balance, aberrantly altered IgA contributes to the pathogenesis of IgA nephropathy and autoimmune encephalitis. To date, IgA-based therapeutics have displayed promising therapeutic efficacy against respiratory disorders, inflammatory bowel diseases and oral fungal infections. Through standardized retrieval and categorical sorting of the published literature covering IgA structure, physiological functions, disease pathogenic mechanisms and therapeutic research, this review systematically organizes relevant research advances, analyzes the bottlenecks and translational prospects of IgA-targeted therapeutics, and provides objective references to accelerate the clinical translation of IgA antibody agents.<\/jats:p>","DOI":"10.3390\/ijms27146471","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:35:52Z","timestamp":1784630152000},"page":"6471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Research Advances and Biological Features of IgA for Immune-Related Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"Han","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghao","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jijun","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9413-2378","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8307-6478","authenticated-orcid":false,"given":"Longlong","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojiang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghua","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiannan","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxia","family":"Qiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1365-3083.2009.02319.x","article-title":"Mucosal Immunity: Induction, Dissemination, and Effector Functions","volume":"70","author":"Brandtzaeg","year":"2009","journal-title":"Scand. J. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"de Sousa-Pereira, P., and Woof, J.M. (2019). IgA: Structure, Function, and Developability. Antibodies, 8.","DOI":"10.3390\/antib8040057"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1146\/annurev-immunol-102119-074236","article-title":"Production and Function of Immunoglobulin A","volume":"39","author":"Hand","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"ref_4","first-page":"559","article-title":"Human Secretory Immunoglobulin M. An Immunochemical and Immunohistochemical Study","volume":"29","author":"Brandtzaeg","year":"1975","journal-title":"Immunology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/mi.2008.68","article-title":"Location of Secretory Component on the Fc Edge of Dimeric IgA1 Reveals Insight into the Role of Secretory IgA1 in Mucosal Immunity","volume":"2","author":"Bonner","year":"2009","journal-title":"Mucosal Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5077","DOI":"10.1074\/jbc.M807529200","article-title":"The Nonplanar Secretory IgA2 and near Planar Secretory IgA1 Solution Structures Rationalize Their Different Mucosal Immune Responses","volume":"284","author":"Bonner","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/mi.2011.41","article-title":"Secretory IgA\u2019s Complex Roles in Immunity and Mucosal Homeostasis in the Gut","volume":"4","author":"Mantis","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Carreto-Binaghi, L.E., Sztein, M.B., and Booth, J.S. (2024). Role of Cellular Effectors in the Induction and Maintenance of IgA Responses Leading to Protective Immunity against Enteric Bacterial Pathogens. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1446072"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.imlet.2003.11.018","article-title":"The Fc Receptor for IgA (Fc\u03b1RI, CD89)","volume":"92","author":"Otten","year":"2004","journal-title":"Immunol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1074\/jbc.273.4.2260","article-title":"The Glycosylation and Structure of Human Serum IgA1, Fab, and Fc Regions and the Role of N-Glycosylation on Fc\u03b1 Receptor Interactions","volume":"273","author":"Mattu","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1016\/j.jaci.2009.09.046","article-title":"Structure and Function of Immunoglobulins","volume":"125","author":"Schroeder","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1042\/bj2710285","article-title":"The Structure and Function of Human IgA","volume":"271","author":"Kerr","year":"1990","journal-title":"Biochem. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Breedveld, A., and van Egmond, M. (2019). IgA and Fc\u03b1RI: Pathological Roles and Therapeutic Opportunities. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00553"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1006\/jmbi.1998.2556","article-title":"The Fab and Fc Fragments of IgA1 Exhibit a Different Arrangement from That in IgG: A Study by X-Ray and Neutron Solution Scattering and Homology Modelling","volume":"286","author":"Boehm","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"207\u2013208, IN17\u2013IN19","DOI":"10.1016\/0022-2836(71)90097-0","article-title":"Electron Microscopy of Human and Mouse Myeloma Serum IgA","volume":"56","author":"Dourmashkin","year":"1971","journal-title":"J. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.4049\/jimmunol.180.2.1008","article-title":"Implications of the Near-Planar Solution Structure of Human Myeloma Dimeric IgA1 for Mucosal Immunity and IgA Nephropathy","volume":"180","author":"Bonner","year":"2008","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/s41422-020-0336-3","article-title":"Structural Insights into Secretory Immunoglobulin a and Its Interaction with a Pneumococcal Adhesin","volume":"30","author":"Wang","year":"2020","journal-title":"Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1126\/science.aaz5807","article-title":"Structure of the Secretory Immunoglobulin A Core","volume":"367","author":"Kumar","year":"2020","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/nature01685","article-title":"Insights into IgA-Mediated Immune Responses from the Crystal Structures of Human Fc\u03b1RI and Its Complex with IgA1-Fc","volume":"423","author":"Herr","year":"2003","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e56098","DOI":"10.7554\/eLife.56098","article-title":"The Structures of Secretory and Dimeric Immunoglobulin a","volume":"9","author":"Parker","year":"2020","journal-title":"eLife"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pan, S., Manabe, N., and Yamaguchi, Y. (2021). 3D Structures of IgA, IgM, and Components. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312776"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhou, J., Wang, J., Shen, J., Lin, Y., Kang, L., Wang, Y., Zhou, Y., Liao, G., and Ren, B. (2026). The Roles of Salivary Secretory IgA on the Development of Oral Candidiasis. Front. Oral Health, 7.","DOI":"10.3389\/froh.2026.1760095"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"297","DOI":"10.25259\/ijn_425_23","article-title":"IgA Nephropathy: Emerging Mechanisms of Disease","volume":"34","author":"Roberts","year":"2024","journal-title":"Indian J. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Knoppova, B., Reily, C., King, R.G., Julian, B.A., Novak, J., and Green, T.J. (2021). Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194501"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00281-012-0306-z","article-title":"Glycosylation of IgA1 and Pathogenesis of IgA Nephropathy","volume":"34","author":"Novak","year":"2012","journal-title":"Semin. Immunopathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"699","DOI":"10.2215\/CJN.0000000000000171","article-title":"Prognosis of IgA Nephropathy: A Lifetime Story","volume":"18","author":"Bharati","year":"2023","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ekir.2017.08.008","article-title":"Life Expectancy for Patients from the Southeastern United States with IgA Nephropathy","volume":"3","author":"Hastings","year":"2017","journal-title":"Kidney Int. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"727","DOI":"10.2215\/CJN.0000000000000135","article-title":"Long-Term Outcomes in IgA Nephropathy","volume":"18","author":"Pitcher","year":"2023","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1093\/ndt\/gfr527","article-title":"Long-Term Renal Survival and Related Risk Factors in Patients with IgA Nephropathy: Results from a Cohort of 1155 Cases in a Chinese Adult Population","volume":"27","author":"Le","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Horgos, M.S., Pop, O.L., Sandor, M., Borza, I.L., Negrean, R.A., Cote, A., Neamtu, A.-A., Grierosu, C., Sachelarie, L., and Huniadi, A. (2023). Platelets Rich Plasma (PRP) Procedure in the Healing of Atonic Wounds. J. Clin. Med., 12.","DOI":"10.3390\/jcm12123890"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Opri\u021bescu, S., Ni\u021bescu, G.V., Golumbeanu, M., Boghi\u021boiu, D., Ioni\u021b\u0103, E.I., Licu, M., Chirigiu, L.-M.-E., Popovici, V., Marin, L.-M., and Moro\u0219an, E. (2025). Serum IgE and IgA Levels in Pediatric Henoch-Sch\u00f6nlein Purpura: Clinical Characteristics and Immunological Correlations in the Context of Infectious Diseases-a Five-Year Retrospective Analysis. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202505.0158.v1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00281-021-00874-9","article-title":"IgA Vasculitis","volume":"43","author":"Pillebout","year":"2021","journal-title":"Semin. Immunopathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/BF00865470","article-title":"Possible Pathogenic Role of IgE in Henoch-Sch\u00f6nlein Purpura","volume":"8","author":"Davin","year":"1994","journal-title":"Pediatr. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/ki.2011.83","article-title":"Inherited IgA Glycosylation Pattern in IgA Nephropathy and HSP Nephritis: Where Do We Go Next?","volume":"80","author":"Boyd","year":"2011","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1212\/WNL.0b013e318258300d","article-title":"IgA NMDA Receptor Antibodies Are Markers of Synaptic Immunity in Slow Cognitive Impairment","volume":"78","author":"Maier","year":"2012","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2147\/ITT.S266242","article-title":"IgA and Fc\u03b1RI: Versatile Players in Homeostasis, Infection, and Autoimmunity","volume":"9","year":"2021","journal-title":"ImmunoTargets Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s00018-018-2976-8","article-title":"The Inflammatory Function of Human IgA","volume":"76","author":"Hansen","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Nagelkerke, S.Q., and Kuijpers, T.W. (2015). Immunomodulation by IVIg and the Role of Fc-Gamma Receptors: Classic Mechanisms of Action after All?. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00674"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/s41577-021-00543-w","article-title":"Autoantibodies in Neurological Disease","volume":"21","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.7555\/JBR.30.20150131","article-title":"Autoantibodies in Alzheimer\u2019s Disease: Potential Biomarkers, Pathogenic Roles, and Therapeutic Implications","volume":"30","author":"Wu","year":"2016","journal-title":"J. Biomed. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41572-025-00650-1","article-title":"Autoimmune Encephalitis","volume":"11","author":"Leypoldt","year":"2025","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Potaczek, D.P., van Tol, B.D.M., Falck, D., Krolczik, C., Zlatina, K., Bertrams, W., Wilhelm, J., Schmeck, B., Seeliger, B., and David, S. (2024). Glycosylation Signature of Plasma IgA of Critically Ill COVID-19 Patients. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1439248"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1021\/acs.jproteome.3c00260","article-title":"Immunoglobulin a Glycosylation Differs between Crohn\u2019s Disease and Ulcerative Colitis","volume":"22","author":"Clerc","year":"2023","journal-title":"J. Proteome Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mayboroda, O.A., Lageveen-Kammeijer, G.S.M., Wuhrer, M., and Dolhain, R.J.E.M. (2023). An Integrated Glycosylation Signature of Rheumatoid Arthritis. Biomolecules, 13.","DOI":"10.3390\/biom13071106"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Brandsma, A.M., Bondza, S., Evers, M., Koutstaal, R., Nederend, M., Jansen, J.H.M., R\u00f6sner, T., Valerius, T., Leusen, J.H.W., and Broeke, T.T. (2019). Potent Fc Receptor Signaling by IgA Leads to Superior Killing of Cancer Cells by Neutrophils Compared to IgG. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00704"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bohl\u00e4nder, F. (2023). A New Hope? Possibilities of Therapeutic IgA Antibodies in the Treatment of Inflammatory Lung Diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1127339"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"van Tetering, G., Evers, M., Chan, C., Stip, M., and Leusen, J. (2020). Fc Engineering Strategies to Advance IgA Antibodies as Therapeutic Agents. Antibodies, 9.","DOI":"10.3390\/antib9040070"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Saito, S., Sano, K., Suzuki, T., Ainai, A., Taga, Y., Ueno, T., Tabata, K., Saito, K., Wada, Y., and Ohara, Y. (2019). IgA Tetramerization Improves Target Breadth but Not Peak Potency of Functionality of Anti-Influenza Virus Broadly Neutralizing Antibody. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007427"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.chom.2020.04.023","article-title":"Identification of Human Single-Domain Antibodies against SARS-CoV-2","volume":"27","author":"Wu","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1038\/s41467-020-18058-8","article-title":"A Cross-Reactive Human IgA Monoclonal Antibody Blocks SARS-CoV-2 Spike-ACE2 Interaction","volume":"11","author":"Ejemel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"El Ansari, Y.S., Kanagaratham, C., Burton, O.T., Santos, J.V., Hollister, B.-M.A., Lewis, O.L., Renz, H., and Oettgen, H.C. (2022). Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.881655"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.cell.2022.03.009","article-title":"Broad Neutralization of SARS-CoV-2 Variants by an Inhalable Bispecific Single-Domain Antibody","volume":"185","author":"Li","year":"2022","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41392-023-01534-0","article-title":"Defining a Highly Conserved Cryptic Epitope for Antibody Recognition of SARS-CoV-2 Variants","volume":"8","author":"Hao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_54","first-page":"501","article-title":"Construction of Secretory IgA against SARS-CoV-2 and Its Biodistribution through Nasal Administration in Mice","volume":"48","author":"Ping","year":"2024","journal-title":"Mil. Med. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2315354120","DOI":"10.1073\/pnas.2315354120","article-title":"Conversion of Monoclonal IgG to Dimeric and Secretory IgA Restores Neutralizing Ability and Prevents Infection of Omicron Lineages","volume":"121","author":"Marcotte","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.ymthe.2025.02.041","article-title":"Nasal Delivery of Secretory IgA Confers Enhanced Neutralizing Activity against Omicron Variants Compared to Its IgG Counterpart","volume":"33","author":"Zhang","year":"2025","journal-title":"Mol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e180784","DOI":"10.1172\/jci.insight.180784","article-title":"An Intranasally Administered Adenovirus-Vectored SARS-CoV-2 Vaccine Induces Robust Mucosal Secretory IgA","volume":"9","author":"Sun","year":"2024","journal-title":"JCI Insight"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e198045","DOI":"10.1172\/jci.insight.198045","article-title":"Intranasal Booster Drives Class Switching and Homing of Memory B Cells for Mucosal IgA Response","volume":"11","author":"Chen","year":"2025","journal-title":"JCI Insight"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"eadz1580","DOI":"10.1126\/scitranslmed.adz1580","article-title":"Phase 1 and Preclinical Studies Reveal Safety, Pharmacokinetics, and Efficacy of Intranasal Delivery of the Influenza Antibody CR9114","volume":"18","author":"Beukenhorst","year":"2026","journal-title":"Sci. Transl. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16103","DOI":"10.1038\/nmicrobiol.2016.103","article-title":"High-Affinity Monoclonal IgA Regulates Gut Microbiota and Prevents Colitis in Mice","volume":"1","author":"Okai","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.mucimm.2023.12.002","article-title":"MZB1-Mediated IgA Secretion Suppresses the Development and Progression of Colorectal Cancer Triggered by Gut Inflammation","volume":"17","author":"Tang","year":"2024","journal-title":"Mucosal Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/s41467-019-08581-8","article-title":"Intestinal Non-Canonical NF\u03baB Signaling Shapes the Local and Systemic Immune Response","volume":"10","author":"Ramakrishnan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2303226","DOI":"10.1080\/21645515.2024.2303226","article-title":"In Vivo Antiviral Efficacy of LCTG-002, a Pooled, Purified Human Milk Secretory IgA Product, against SARS-CoV-2 in a Murine Model of COVID-19","volume":"20","author":"Mane","year":"2024","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_64","unstructured":"(2026, April 09). Lactiga Secures Multi-Year, Multi-Million Dollar Grant from NIH\u2019s National Institute of Allergy and Infectious Diseases to Advance Groundbreaking, Mucosal-Targeted Secretory IgA for Immunodeficient Patients. Available online: https:\/\/www.businesswire.com\/news\/home\/20250203344756\/en\/Lactiga-Secures-Multi-Year-Multi-Million-Dollar-Grant-from-NIHs-National-Institute-of-Allergy-and-Infectious-Diseases-to-Advance-Groundbreaking-Mucosal-Targeted-Secretory-IgA-for-Immunodeficient-Patients."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13613-020-00740-1","article-title":"Best-Practice IgM- and IgA-Enriched Immunoglobulin Use in Patients with Sepsis","volume":"10","author":"Nierhaus","year":"2020","journal-title":"Ann. Intensive Care"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Keyt, B.A., Baliga, R., Sinclair, A.M., Carroll, S.F., and Peterson, M.S. (2020). Structure, Function, and Therapeutic Use of IgM Antibodies. Antibodies, 9.","DOI":"10.3390\/antib9040053"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e13101","DOI":"10.1111\/sji.13101","article-title":"Intravenous Immunoglobulin as an Important Adjunct in the Prevention and Therapy of Coronavirus 2019 Disease","volume":"94","author":"Danieli","year":"2021","journal-title":"Scand. J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s13054-022-04059-0","article-title":"Intravenous IgM-Enriched Immunoglobulins in Critical COVID-19: A Multicentre Propensity-Weighted Cohort Study","volume":"26","author":"Rahmel","year":"2022","journal-title":"Crit. Care"},{"key":"ref_69","unstructured":"Biotest (2026, March 25). A Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Phase III Trial to Assess the Efficacy and Safety of Trimodulin (BT588) in Adult Hospitalized Subjects with CAP Including COVID-19 Pneumonia, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05531149."},{"key":"ref_70","unstructured":"Biotest (2026, March 25). A Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Phase III Trial to Assess the Efficacy and Safety of Trimodulin (BT588) in Adult Hospitalized Subjects with Severe Community-Acquired Pneumonia (sCAP), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05722938."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41586-021-03722-w","article-title":"Adaptive Immunity Induces Mutualism between Commensal Eukaryotes","volume":"596","author":"Ost","year":"2021","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s00253-024-13063-z","article-title":"Secretory IgA Reduced the Ergosterol Contents of Candida Albicans to Repress Its Hyphal Growth and Virulence","volume":"108","author":"Wang","year":"2024","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1111\/pbi.14576","article-title":"Enhancing Quality and Yield of Recombinant Secretory IgA Antibodies in Nicotiana Benthamiana by Endoplasmic Reticulum Engineering","volume":"23","author":"Melnik","year":"2025","journal-title":"Plant Biotechnol. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6","DOI":"10.31083\/j.fbe1501006","article-title":"Use of Probiotics for Oral Candidiasis: State of the Art and Perspective. A Further Step Toward Personalized Medicine?","volume":"15","author":"Contaldo","year":"2023","journal-title":"Front. Biosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"117624","DOI":"10.1016\/j.jpba.2026.117624","article-title":"Dissection of Potential Mechanism of Bao-Yuan Tablet against Spleen-Qi Deficiency by UPLC-Q\/TOF MS and Network Pharmacology","volume":"280","author":"Chen","year":"2026","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_76","first-page":"331","article-title":"Estimation of the Intravascular Half-Lives of Normal Rhesus Monkey IgG, IgA and IgM","volume":"36","author":"Challacombe","year":"1979","journal-title":"Immunology"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Vattepu, R., Sneed, S.L., and Anthony, R.M. (2022). Sialylation as an Important Regulator of Antibody Function. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.818736"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"111210","DOI":"10.1016\/j.jbc.2026.111210","article-title":"Engineered IgA-Fc Fusion Protein with Bioactive Nanobody Neutralizes SARS-CoV-2 Variants with Mucosal Delivery Potential","volume":"302","author":"Golonka","year":"2026","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.chembiol.2014.10.017","article-title":"IgGA: A \u201cCross-Isotype\u201d Engineered Human Fc Antibody Domain That Displays Both IgG-like and IgA-like Effector Functions","volume":"21","author":"Kelton","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1080\/19420862.2019.1622940","article-title":"Production, Characterization, and In Vivo Half-Life Extension of Polymeric IgA Molecules in Mice","volume":"11","author":"Lombana","year":"2019","journal-title":"mAbs"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4049\/jimmunol.1601775","article-title":"Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems","volume":"199","author":"Boyaka","year":"2017","journal-title":"J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"11101","DOI":"10.1038\/s41598-024-61341-7","article-title":"Secretory IgA and Course of COVID-19 in Patients Receiving a Bacteria-Based Immunostimulant Agent in Addition to Background Therapy","volume":"14","author":"Kostinov","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2031483","DOI":"10.1080\/19420862.2022.2031483","article-title":"Therapeutic Antibodies for COVID-19: Is a New Age of IgM, IgA and Bispecific Antibodies Coming?","volume":"14","author":"Zhang","year":"2022","journal-title":"mAbs"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6471\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:38:52Z","timestamp":1784630332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":83,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146471"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146471","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}