Martelius, Timi

Seppänen, Mikko R. J.

Warnatz, Klaus

English

PubMed

Helsingin yliopiston digitaalinen arkisto

https://helda.helsinki.fiEditorial : Updates on the pathogenesis of common variableimmunodeficiency (CVID)Martelius, Timi2023-01-10Martelius , T , Seppänen , M R J & Warnatz , K 2023 , ' Editorial : Updates on thepathogenesis of common variable immunodeficiency (CVID) ' , Frontiers in Immunology , vol.13 , 1130418 . https://doi.org/10.3389/fimmu.2022.1130418http://hdl.handle.net/10138/356286https://doi.org/10.3389/fimmu.2022.1130418cc_bypublishedVersionDownloaded from Helda, University of Helsinki institutional repository.This is an electronic reprint of the original article.This reprint may differ from the original in pagination and typographic detail.Please cite the original version.Frontiers in ImmunologyOPEN ACCESSEDITED AND REVIEWED BYFabio Candotti,Centre Hospitalier Universitaire Vaudois(CHUV), Switzerland*CORRESPONDENCETimi Marteliustimi.martelius@hus.fiSPECIALTY SECTIONThis article was submitted toPrimary Immunodeficiencies,a section of the journalFrontiers in ImmunologyRECEIVED 23 December 2022ACCEPTED 30 December 2022PUBLISHED 10 January 2023CITATIONMartelius T, Seppänen MRJ and Warnatz K(2023) Editorial: Updates on thepathogenesis of common variableimmunodeficiency (CVID).Front. Immunol. 13:1130418.doi: 10.3389/fimmu.2022.1130418COPYRIGHT© 2023 Martelius, Seppänen and Warnatz.This is an open-access article distributedunder the terms of the Creative CommonsAttribution License (CC BY). The use,distribution or reproduction in otherforums is permitted, provided the originalauthor(s) and the copyright owner(s) arecredited and that the original publication inthis journal is cited, in accordance withaccepted academic practice. No use,distribution or reproduction is permittedwhich does not comply with these terms.TYPE EditorialPUBLISHED 10 January 2023DOI 10.3389/fimmu.2022.1130418Editorial: Updates on thepathogenesis of common variableimmunodeficiency (CVID)Timi Martelius1*, Mikko R. J. Seppänen2 and Klaus Warnatz31Inflammation Center, Infectious Diseases, HUS Helsinki University Hospital and University of Helsinki,Helsinki, Finland, 2Rare Disease and Pediatric Research Centers, New Children’s Hospital, HUS HelsinkiUniversity Hospital and University of Helsinki, Helsinki, Finland, 3Department of Rheumatology andClinical Immunology, Medical Center, University of Freiburg, Freiburg, GermanyKEYWORDSinborn errors in immunity, primary immunodeficiency, primary antibody deficiencies,common variable immune deficiency (CVID), geneticsEditorial on the Research TopicUpdates on the pathogenesis of common variable immunodefi-ciency (CVID)Common variable immunodeficiency (CVID) is the most common clinically manifestinborn error of immunity. Definitions of CVID have evolved over years. Infections orautoimmunity and lymphoproliferation, decreased IgG and IgA, together with impairedvaccine responses and low class-switched memory B cells have been the cardinal featuresof CVID.Despite advances in genetics and discovery of numerous monogenic inborn errors ofimmunity under the CVID “umbrella” in the majority of CVID cases we do not understandthe cause of the disease. Interestingly, from monogenic disorders we have learned thatpathogenic variants of a wide variety of genes involving many different pathways can presentwith the clinical features of CVID. Some of the underlying genetic defects in CVID patients,like STAT3 gain-of-function, hypomorphic RAG and ADA2 demonstrate that evenpathogenic variants in genes usually associated with different classes of IEIs according tothe IUIS classification may clinically present as CVID.Currently, in the remaining majority of CVID:s without a genetic diagnosis, there may beyet unknown genetic, epigenetic, or acquired causes. The defects may also affect nichesoutside lymphocyte populations such as the bone marrow, lymph node orthymic microenvironment.In the absence of genetic diagnosis, alterations of differentiation, function and numbers ofB and T cells, in patients with CVID may give clues on relevant pathomechanisms of thedisease. For example, decreased class switched memory B-cells suggest a failure in germinalcenter output. This is often seen in CVIDs both without and with known genetic etiology.This special series on the pathogenesis of CVID comprises three literature reviews on newperspectives to CVID and two original studies. First, Ho et al. summarize what is knownabout biomarkers in CVID and how these relate to different complications andpathogenetic mechanisms.Fekrvand et al. review what is known about circulating B and T cell subset alterations inthe reported monogenic CVID like diseases. Still, the number of patients carrying certaingene defects remains small and differentiating cellular patterns are not always found.frontiersin.org01Martelius et al. 10.3389/fimmu.2022.1130418Gupta et al. review the data on regulatory T- and B cell subsets inCVID and their role in normal physiology. Schouwenburg et al.investigate the altered differentiation of B cells within secondarylymphoid organs of three CVID patients by combining analysis ofperipheral blood B-cell subsets with histological, flow cytometric andfunctional analysis of B-cells in the lymph nodes and tonsils.Heterogeneity of disturbed germinal center output within CVID iswell demonstrated, even by such a small patient cohort.Last, Guevara-Hoyer et al. investigate the prevalence of CVID-associated pathogenic gene variants in non-Hodgkin lymphomas. Theincidence of lymphoma in CVID is greatly increased. Pathogenicvariants in the genes involved in B-cell development anddifferentiation have been detected in B-cell leukemias andlymphomas. Here, the authors found that 25% of non-Hodgkinlymphomas harbored variants in genes associated with monogenicCVID, PIK3CD and STAT3 being most commonly involved.Many open questions remain due to the coincidence of rarity andheterogeneity of CVID. With emerging novel technologies andincreasing understanding of the human immune system, there ishope that these roads lead to new original research and betterunderstanding of the complex pathophysiology of CVID - whichuntil now has been is only fragmentarily understood.Author contributionsAll authors (TM, MS, KW) jointly concepted and wrote theeditorial and agree to be accountable for the content of the work.Frontiers in Immunology 02All authors contributed to the article and approved thesubmitted version.FundingFinnish Foundation for Paediatric Research (MS), HelsinkiUniversity Central Hospital Research Funds (TM, MS), Jane andAatos Erkko Foundation (MS), the “Netzwerke SeltenerErkrankungen” by the Bundesministerium für Bildung undForschung (BMBF), grant code: GAIN_01GM1910A to KW.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of the authorsand do not necessarily represent those of their affiliated organizations,or those of the publisher, the editors and the reviewers. Any productthat may be evaluated in this article, or claim that may be made by itsmanufacturer, is not guaranteed or endorsed by the publisher.frontiersin.org

Editorial : Updates on the pathogenesis of common variable immunodeficiency (CVID)

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Editorial: Updates on the pathogenesis of common variable immunodeficiency (CVID)

Seppanen, Mikko R. J.

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Editorial : Updates on the pathogenesis of common variable immunodeficiency (CVID)

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