Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling

作     者：Kelly A.Dingess Max Hoek Danique M.Hvan Rijswijk Sem Tamara Maurits Aden Boer Tim Veth Mirjam J.A.Damen Arjan Barendregt Michelle Romijn Hannah G.Juncker Britt Jvan Keulen Gestur Vidarsson Johannes Bvan Goudoever Albert Bondt Albert J.R.Heck 

作者机构：Biomolecular Mass Spectrometry and ProteomicsBijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical SciencesUniversity of UtrechtPadualaan 8Utrecht 3584 CHThe Netherlands Netherlands Proteomics CenterPadualaan 8Utrecht 3584 CHThe Netherlands Amsterdam UMCVrije UniversiteitUniversity of AmsterdamEmma Children’s HospitalAmsterdam Reproduction&Development Research InstituteDepartment of PediatricsAmsterdamthe Netherlands Department of Experimental ImmunohematologySanquin Research and Landsteiner LaboratoryAmsterdam UMCUniversity of AmsterdamAmsterdamNetherlands 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2023年第20卷第1期

页      面：26-37页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：support from the Netherlands Organization for Scientific Research(NOW)funding the Netherlands Proteomics Centre through the X-omics Road Map program(project 184.034.019)and Gravitation Subgrant 00022 from the Institute for Chemical Immunology.AJRH acknowledges support from the Netherlands Organization for Scientific Research(NOW)through the Spinoza Award SPI.2017.028 to AJRH.The COVID MILK studies was funded by Stichting Steun Emma Kinderziekenhuis.KAD acknowledges the Amsterdam Reproduction and Development Institute for funding this work though the AR&D grant(V.000296) 

主　　题：Antigen binding fragment Immunoglobulin A1 Clonal repertoires human milk Serum 

摘      要：The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (J-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a J-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and J-chain coupled dimeric IgA1. The serum dimeric J-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins;one of these produces dimeric J-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum.