Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid

Stephanie Goletz; Manuela Pigors; Tina Rastegar Lari; Christoph M Hammers; Yao Wang; Shirin Emtenani; Monique Aumailley; Maike M Holtsche; Felix H Stang; Imke Weyers; Inke R König; Cristina Has; Christiane Radzimski; Lars Komorowski; Detlef Zillikens; Enno Schmidt

doi:10.1016/j.jaad.2023.11.014

Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid

Stephanie Goletz, Manuela Pigors, Tina Rastegar Lari, Christoph M Hammers, Yao Wang, Shirin Emtenani, Monique Aumailley, Maike M Holtsche, Felix H Stang, Imke Weyers, Inke R König, Cristina Has, Christiane Radzimski, Lars Komorowski, Detlef Zillikens, Enno Schmidt

33 Zitate (Scopus)

Abstract

BACKGROUND: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies.

OBJECTIVE: To identify a target antigen with higher clinical and diagnostic relevance.

METHODS: Immunoprecipitation, mass spectrometry, and immunoblotting were employed for analysis of skin extracts and sera of patients with anti-p200 pemphigoid (n = 60), other AIBD (n = 33), and healthy blood donors (n = 29). To localize the new antigen in skin, cultured keratinocytes and fibroblasts, quantitative real-time polymerase chain reaction and immunofluorescence microscopy were performed.

RESULTS: Laminin β4 was identified as target antigen of anti-p200 pemphigoid in all analyzed patients. It was located at the level of the basement membrane zone of the skin with predominant expression in keratinocytes.

LIMITATIONS: A higher number of sera needs to be tested to verify that laminin β4 is the diagnostically relevant antigen of anti-p200 pemphigoid.

CONCLUSION: The identification of laminin β4 as an additional target antigen in anti-p200 pemphigoid will allow its differentiation from other AIBD and as such, improve the management of these rare disorders.

Originalsprache	Englisch
Zeitschrift	Journal of the American Academy of Dermatology
Jahrgang	90
Ausgabenummer	4
Seiten (von - bis)	790-797
Seitenumfang	8
ISSN	0190-9622
DOIs	https://doi.org/10.1016/j.jaad.2023.11.014
Publikationsstatus	Veröffentlicht - 04.2024

Fördermittel

Funding sources: Supported by the German Research Foundation through the Schleswig-Holstein Excellence Cluster “Precision Medicine in Chronic Inflammation” (DFG EXC 2167/1, TI-3 to E.S.), the CRU 303 “Pemphigoid Diseases” (to E.S., D.Z., and I.R.K.), and the CRC 1526 “Pathomechanisms of Antibody-mediated Autoimmunity” (to E.S., C.M.H., and D.Z.) as well as research grants from the University of Lübeck (CS06-2019 to C.M.H., J08-2021 to M.P., and J13-2022 to S.E.).

Träger	Trägernummer
Deutsche Forschungsgemeinschaft	CRU 303, EXC 2167/1, CRC 1526, TI-3
Universität zu Lübeck	CS06-2019, J08-2021, J13-2022

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)
Zentren: Center for Research on Inflammation of the Skin (CRIS)

DFG-Fachsystematik

2.21-05 Immunologie
2.22-19 Dermatologie

Dokumente

10.1016/j.jaad.2023.11.014

Weitere Links

SFB 1526, PANTAU: Pathomechanismen Antikörpervermittelter Autoimmunerkrankungen
Sadik, C. (Sprecher*in), Zillikens, D. (Sprecher*in), Scheffold, A. (Projektleiter*in (PI)), Schmidt, E. (Projektleiter*in (PI)), Heine, G. (Projektleiter*in (PI)), Manz, R. (Projektleiter*in (PI)), Köhl, J. (Projektleiter*in (PI)), Ludwig, R. (Projektleiter*in (PI)), Peipp, M. (Projektleiter*in (PI)), Hammers, M. C. (Projektleiter*in (PI)), Verschoor, A. (Projektleiter*in (PI)), Karsten, C. (Projektleiter*in (PI)), Nimmerjahn, F. (Projektleiter*in (PI)), Hutloff, A. (Projektleiter*in (PI)), Ibrahim, S. (Projektleiter*in (PI)), Wettschureck, N. (Projektleiter*in (PI)), Bieber, K. (Projektleiter*in (PI)), Schilf, P. (Projektleiter*in (PI)), Vaeth, M. (Projektleiter*in (PI)), Hirose, M. (Projektleiter*in (PI)), Vaeth, M. (Projektleiter*in (PI)), Baines, J. F. (Projektleiter*in (PI)), Bacher, P. (Projektleiter*in (PI)), Hoffmann, M. (Projektleiter*in (PI)), Busch, H. S. (Projektleiter*in (PI)), Höppner, M. (Projektleiter*in (PI)), Becker, M. (Projektleiter*in (PI)), Holtsche, M. M. (Projektleiter*in (PI)), Fähnrich, A. (Projektleiter*in (PI)), Szymczak, S. (Projektleiter*in (PI)), Murthy, S. (Projektleiter*in (PI)) & Lux, A. (Projektleiter*in (PI))
01.01.22 → 31.12.27
Projekt: DFG Verbundprojekte › DFG Sonderforschungsbereiche / Transregios (SFB/TR)

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Goletz, S., Pigors, M., Lari, T. R., Hammers, C. M., Wang, Y., Emtenani, S., Aumailley, M., Holtsche, M. M., Stang, F. H., Weyers, I., König, I. R., Has, C., Radzimski, C., Komorowski, L., Zillikens, D., & Schmidt, E. (2024). Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid. Journal of the American Academy of Dermatology, 90(4), 790-797. https://doi.org/10.1016/j.jaad.2023.11.014

@article{bbd023c844f14d259432c80fae27fb8d,

title = "Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid",

abstract = "BACKGROUND: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70\% to 90\% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies.OBJECTIVE: To identify a target antigen with higher clinical and diagnostic relevance.METHODS: Immunoprecipitation, mass spectrometry, and immunoblotting were employed for analysis of skin extracts and sera of patients with anti-p200 pemphigoid (n = 60), other AIBD (n = 33), and healthy blood donors (n = 29). To localize the new antigen in skin, cultured keratinocytes and fibroblasts, quantitative real-time polymerase chain reaction and immunofluorescence microscopy were performed.RESULTS: Laminin β4 was identified as target antigen of anti-p200 pemphigoid in all analyzed patients. It was located at the level of the basement membrane zone of the skin with predominant expression in keratinocytes.LIMITATIONS: A higher number of sera needs to be tested to verify that laminin β4 is the diagnostically relevant antigen of anti-p200 pemphigoid.CONCLUSION: The identification of laminin β4 as an additional target antigen in anti-p200 pemphigoid will allow its differentiation from other AIBD and as such, improve the management of these rare disorders.",

author = "Stephanie Goletz and Manuela Pigors and Lari, \{Tina Rastegar\} and Hammers, \{Christoph M\} and Yao Wang and Shirin Emtenani and Monique Aumailley and Holtsche, \{Maike M\} and Stang, \{Felix H\} and Imke Weyers and K{\"o}nig, \{Inke R\} and Cristina Has and Christiane Radzimski and Lars Komorowski and Detlef Zillikens and Enno Schmidt",

year = "2024",

month = apr,

doi = "10.1016/j.jaad.2023.11.014",

language = "English",

volume = "90",

pages = "790--797",

journal = "Journal of the American Academy of Dermatology",

issn = "0190-9622",

publisher = "Elsevier Inc.",

number = "4",

}

Goletz, S , Pigors, M, Lari, TR, Hammers, CM, Wang, Y, Emtenani, S, Aumailley, M, Holtsche, MM, Stang, FH, Weyers, I , König, IR, Has, C, Radzimski, C, Komorowski, L, Zillikens, D & Schmidt, E 2024, 'Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid', Journal of the American Academy of Dermatology, Jg. 90, Nr. 4, S. 790-797. https://doi.org/10.1016/j.jaad.2023.11.014

Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid. / Goletz, Stephanie ; Pigors, Manuela; Lari, Tina Rastegar et al.
in: Journal of the American Academy of Dermatology, Jahrgang 90, Nr. 4, 04.2024, S. 790-797.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid

AU - Goletz, Stephanie

AU - Pigors, Manuela

AU - Lari, Tina Rastegar

AU - Hammers, Christoph M

AU - Wang, Yao

AU - Emtenani, Shirin

AU - Aumailley, Monique

AU - Holtsche, Maike M

AU - Stang, Felix H

AU - Weyers, Imke

AU - König, Inke R

AU - Has, Cristina

AU - Radzimski, Christiane

AU - Komorowski, Lars

AU - Zillikens, Detlef

AU - Schmidt, Enno

PY - 2024/4

Y1 - 2024/4

N2 - BACKGROUND: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies.OBJECTIVE: To identify a target antigen with higher clinical and diagnostic relevance.METHODS: Immunoprecipitation, mass spectrometry, and immunoblotting were employed for analysis of skin extracts and sera of patients with anti-p200 pemphigoid (n = 60), other AIBD (n = 33), and healthy blood donors (n = 29). To localize the new antigen in skin, cultured keratinocytes and fibroblasts, quantitative real-time polymerase chain reaction and immunofluorescence microscopy were performed.RESULTS: Laminin β4 was identified as target antigen of anti-p200 pemphigoid in all analyzed patients. It was located at the level of the basement membrane zone of the skin with predominant expression in keratinocytes.LIMITATIONS: A higher number of sera needs to be tested to verify that laminin β4 is the diagnostically relevant antigen of anti-p200 pemphigoid.CONCLUSION: The identification of laminin β4 as an additional target antigen in anti-p200 pemphigoid will allow its differentiation from other AIBD and as such, improve the management of these rare disorders.

AB - BACKGROUND: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies.OBJECTIVE: To identify a target antigen with higher clinical and diagnostic relevance.METHODS: Immunoprecipitation, mass spectrometry, and immunoblotting were employed for analysis of skin extracts and sera of patients with anti-p200 pemphigoid (n = 60), other AIBD (n = 33), and healthy blood donors (n = 29). To localize the new antigen in skin, cultured keratinocytes and fibroblasts, quantitative real-time polymerase chain reaction and immunofluorescence microscopy were performed.RESULTS: Laminin β4 was identified as target antigen of anti-p200 pemphigoid in all analyzed patients. It was located at the level of the basement membrane zone of the skin with predominant expression in keratinocytes.LIMITATIONS: A higher number of sera needs to be tested to verify that laminin β4 is the diagnostically relevant antigen of anti-p200 pemphigoid.CONCLUSION: The identification of laminin β4 as an additional target antigen in anti-p200 pemphigoid will allow its differentiation from other AIBD and as such, improve the management of these rare disorders.

UR - https://www.scopus.com/pages/publications/85179497409

UR - https://www.mendeley.com/catalogue/708e38d1-7338-37c1-a0cd-8d41ac0ca88f/

U2 - 10.1016/j.jaad.2023.11.014

DO - 10.1016/j.jaad.2023.11.014

M3 - Journal articles

C2 - 37992812

SN - 0190-9622

VL - 90

SP - 790

EP - 797

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

IS - 4

ER -

Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid

Abstract

Fördermittel

UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

Dokumente

Weitere Links

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Projekte

SFB 1526, PANTAU: Pathomechanismen Antikörpervermittelter Autoimmunerkrankungen

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