Pathogenic relevance of antibodies against desmoglein 3 in patients with oral lichen planus.

autoantibodies desmoglein 3 oral lichen planus

Journal

Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG
ISSN: 1610-0387
Titre abrégé: J Dtsch Dermatol Ges
Pays: Germany
ID NLM: 101164708

Informations de publication

Date de publication:
16 Aug 2024
Historique:
received: 01 02 2024
accepted: 13 06 2024
medline: 17 8 2024
pubmed: 17 8 2024
entrez: 17 8 2024
Statut: aheadofprint

Résumé

Oral lichen planus (OLP) is a T cell driven disorder that significantly impairs patients' quality of life. Previous reports suggest that both cellular and humoral activities against desmoglein (dsg) 1 and 3 may be involved in OLP pathogenesis. Here, we aim to analyze the frequency of occurrence and pathological significance of anti-dsg antibodies in a large cohort of OLP patients. OLP patients were screened for anti-dsg antibodies by enzyme-linked immunosorbent assay in three tertiary referral centers. OLP sera with anti-dsg antibodies were further analyzed by Western blot and dispase-based keratinocyte dissociation assay (DDA) to identify the targeted dsg ectodomains and to assess their pathogenicity. Of 151-screened individuals with OLP, only four patients (2.6%) with erosive OLP showed serum IgG against dsg1/3. Western blot analysis with recombinant dsg3 ectodomains revealed preferential recognition of the extracellular domain 5. By DDA with spontaneously immortalized human keratinocytes, none of the sera from these four patients induced acantholysis. Activation of humoral immunity occurs prevalently in patients with erosive OLP, probably due to epitope spreading. OLP serum antibodies are unable to induce loss of intercellular adhesion in vitro, strongly suggesting that they are not disease causing but rather an epiphenomenon.

Sections du résumé

BACKGROUND AND OBJECTIVES OBJECTIVE
Oral lichen planus (OLP) is a T cell driven disorder that significantly impairs patients' quality of life. Previous reports suggest that both cellular and humoral activities against desmoglein (dsg) 1 and 3 may be involved in OLP pathogenesis. Here, we aim to analyze the frequency of occurrence and pathological significance of anti-dsg antibodies in a large cohort of OLP patients.
MATERIALS AND METHODS METHODS
OLP patients were screened for anti-dsg antibodies by enzyme-linked immunosorbent assay in three tertiary referral centers. OLP sera with anti-dsg antibodies were further analyzed by Western blot and dispase-based keratinocyte dissociation assay (DDA) to identify the targeted dsg ectodomains and to assess their pathogenicity.
RESULTS RESULTS
Of 151-screened individuals with OLP, only four patients (2.6%) with erosive OLP showed serum IgG against dsg1/3. Western blot analysis with recombinant dsg3 ectodomains revealed preferential recognition of the extracellular domain 5. By DDA with spontaneously immortalized human keratinocytes, none of the sera from these four patients induced acantholysis.
CONCLUSIONS CONCLUSIONS
Activation of humoral immunity occurs prevalently in patients with erosive OLP, probably due to epitope spreading. OLP serum antibodies are unable to induce loss of intercellular adhesion in vitro, strongly suggesting that they are not disease causing but rather an epiphenomenon.

Identifiants

pubmed: 39152677
doi: 10.1111/ddg.15510
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.

Références

Solimani F, Forchhammer S, Schloegl A, et al. Lichen planus – a clinical guide. J Dtsch Dermatol Ges. 2021;19:864‐882.
Didona D, Caposiena Caro RD, Sequeira Santos AM, et al. Therapeutic strategies for oral lichen planus: State of the art and new insights. Front Med (Lausanne). 2022;9:997190.
Laniosz V, Torgerson RR, Ramos‐Rodriguez AJ, et al. Incidence of squamous cell carcinoma in oral lichen planus: A 25‐year population‐based study. Int J Dermatol. 2019;58:296‐301.
Pietschke K, Holstein J, Meier K, et al. The inflammation in cutaneous lichen planus is dominated by IFN‐Upsilon and IL‐21‐A basis for therapeutic JAK1 inhibition. Exp Dermatol. 2021;30:262‐270.
Schmidt T, Solimani F, Pollmann R, et al. T(H)1/T(H)17 cell recognition of desmoglein 3 and bullous pemphigoid antigen 180 in patients with lichen planus. J Allergy Clin Immunol. 2018;142:669‐672 e7.
Sekiya A, Kodera M, Yamaoka T, et al. A case of lichen planus pemphigoides with autoantibodies to the NC16a and C‐terminal domains of BP180 and to desmoglein‐1. Br J Dermatol. 2014;171:1230‐1235.
Kinjyo C, Kaneko T, Korekawa A, et al. Oral lichen planus with antibodies to desmogleins 1 and 3. J Dermatol. 2015;42:40‐41.
Didona D, Hertl M. Detection of anti‐desmoglein antibodies in oral lichen planus: What do we know so far. Front Immunol. 2022;13:1001970.
Vahide L, Zahra H, Forugh G, Nazi S. Autoantibodies to desmogleins 1 and 3 in patients with lichen planus. Arch Dermatol Res. 2017;309:579‐583.
Herrero‐Gonzalez JE, Parera Amer E, Segura S, et al. Epithelial antigenic specificities of circulating autoantibodies in mucosal lichen planus. Int J Dermatol. 2016;55:634‐639.
Didona D, Schmidt MF, Maglie R, Solimani F. Pemphigus and pemphigoids: Clinical presentation, diagnosis and therapy. J Dtsch Dermatol Ges. 2023;21(10):1188‐1209.
Ormond M, McParland H, Thakrar P, et al. Validation of an Oral Disease Severity Score for use in oral lichen planus. Br J Dermatol. 2022;186:1045‐1047.
Escudier M, Ahmed N, Shirlaw P, et al. A scoring system for mucosal disease severity with special reference to oral lichen planus. Br J Dermatol. 2007;157:765‐70.
Muller R, Svoboda V, Wenzel E, et al. IgG reactivity against non‐conformational NH‐terminal epitopes of the desmoglein 3 ectodomain relates to clinical activity and phenotype of pemphigus vulgaris. Exp Dermatol. 2006;15:606‐614.
Schmidt MF, Feoktistova M, Panayotova‐Dimitrova D, et al. Pitfalls in the application of dispase‐based keratinocyte dissociation assay for in vitro analysis of pemphigus vulgaris. Vaccines (Basel). 2022;10(2):208.
Solimani F, Meier K, Zimmer CL, Hashimoto T. Immune serological diagnosis of pemphigus. Ital J Dermatol Venerol. 2021;156:151‐160.
Solimani F, Maglie R, Pollmann R, et al. Thymoma‐associated paraneoplastic autoimmune multiorgan syndrome‐from pemphigus to lichenoid dermatitis. Front Immunol. 2019;10:1413.
Gholizadeh N, Khoini Poorfar H, TaghaviZenouz A, et al. Comparison of serum autoantibodies to desmogleins I, III in patients with oral lichen planus and healthy controls. Iran J Pathol. 2015;10:136‐140.
Rambhia KD, Kharkar V, Pradhan V, et al. A study of prevalence of autoantibodies in patients with lichen planus from Mumbai, India. Indian J Dermatol Venereol Leprol. 2018;84:667‐671.
Lukac J, Brozovic S, Vucicevic‐Boras V, et al. Serum autoantibodies to desmogleins 1 and 3 in patients with oral lichen planus. Croat Med J. 2006;47:53‐58.
Chan LS, Vanderlugt CJ, Hashimoto T, et al. Epitope spreading: lessons from autoimmune skin diseases. J Invest Dermatol. 1998;110:103‐109.
Boch K, Drager S, Zillikens D, et al. Immunization with desmoglein 3 induces non‐pathogenic autoantibodies in mice. PLoS One. 2021;16:e0259586.
Nakahara T, Takagi A, Yamagami J, et al. High anti‐desmoglein 3 antibody ELISA index and negative indirect immunofluorescence result in a patient with pemphigus vulgaris in remission: evaluation of the antibody profile by newly developed methods. JAMA Dermatol. 2014;150:1327‐1330.
Yamagami J, Kacir S, Ishii K, et al. Antibodies to the desmoglein 1 precursor proprotein but not to the mature cell surface protein cloned from individuals without pemphigus. J Immunol. 2009;183:5615‐5621.
Kamiya K, Aoyama Y, Shirafuji Y, et al. Detection of antibodies against the non‐calcium‐dependent epitopes of desmoglein 3 in pemphigus vulgaris and their pathogenic significance. Br J Dermatol. 2012;167:252‐261.
Sharma PM, Choi EJ, Kuroda K, et al. Pathogenic anti‐desmoglein MAbs show variable ELISA activity because of preferential binding of mature versus proprotein isoforms of desmoglein 3. J Invest Dermatol. 2009;129:2309‐2312.
Muramatsu K, Nishie W, Natsuga K, et al. Two cases of erosive oral lichen planus with autoantibodies to desmoglein 3. J Dermatol. 2016;43:1350‐1353.
Oyama N, Chan I, Neill SM, et al. Autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Lancet. 2003;362:118‐123.
Getsios S, Simpson CL, Kojima S, et al. Desmoglein 1‐dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis. J Cell Biol. 2009;185:1243‐1258.
Shimada K, Ochiai T, Shen FC, Hasegawa H. Phenotypic alteration of basal cells in oral lichen planus; switching keratin 19 and desmoglein 1 expression. J Oral Sci. 2018;60:507‐513.
Spindler V, Heupel WM, Efthymiadis A, et al. Desmocollin 3‐mediated binding is crucial for keratinocyte cohesion and is impaired in pemphigus. J Biol Chem. 2009;284:30556‐30564.
Amber KT, Valdebran M, Grando SA. Non‐desmoglein antibodies in patients with pemphigus vulgaris. Front Immunol. 2018;9:1190.
Ishii N. Significance of anti‐desmocollin autoantibodies in pemphigus. J Dermatol. 2023;50:132‐139.
Hudemann C, Maglie R, Llamazares‐Prada M, et al. Human desmocollin 3‒specific IgG antibodies are pathogenic in a humanized HLA class II transgenic mouse model of pemphigus. J Invest Dermatol. 2022;142:915‐923 e3.

Auteurs

Dario Didona (D)

Department of Dermatology and Allergology, Philipps University, Marburg, Germany.

Morna F Schmidt (MF)

Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany.

Katharina Meier (K)

Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Alberto Mesas-Fernandez (A)

Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Roberto Maglie (R)

Section of Dermatology, Department of Health Sciences, University of Florence, Florence, Italy.

Emiliano Antiga (E)

Section of Dermatology, Department of Health Sciences, University of Florence, Florence, Italy.

Marisa Klemp (M)

Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Amir S Yazdi (AS)

Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany.

Kamran Ghoreschi (K)

Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Michael Hertl (M)

Department of Dermatology and Allergology, Philipps University, Marburg, Germany.

Christian Möbs (C)

Department of Dermatology and Allergology, Philipps University, Marburg, Germany.

Farzan Solimani (F)

Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, Berlin, Germany.

Classifications MeSH