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^*

^*Corresponding author for this work

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.

Original language	English
Journal	Journal of the American Academy of Dermatology
ISSN	0190-9622
DOIs	https://doi.org/10.1016/j.jaad.2023.11.014
Publication status	Published - 2023

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

2.22-19 Dermatology
2.21-05 Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jaad.2023.11.014

Cite this

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. (2023). 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. https://doi.org/10.1016/j.jaad.2023.11.014

@article{14479c207e524429b1462cb61d0bbbe6,

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",

note = "Publisher Copyright: {\textcopyright} 2023 American Academy of Dermatology, Inc.",

year = "2023",

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

language = "English",

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

issn = "0190-9622",

}

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 2023, '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. https://doi.org/10.1016/j.jaad.2023.11.014

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 - 2023

Y1 - 2023

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 - http://www.scopus.com/inward/record.url?scp=85179497409&partnerID=8YFLogxK

U2 - 10.1016/j.jaad.2023.11.014

DO - 10.1016/j.jaad.2023.11.014

M3 - Journal articles

C2 - 37992812

AN - SCOPUS:85179497409

SN - 0190-9622

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

ER -

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

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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Other files and links

Fingerprint

CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

Cite this

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

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

Cite this