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Journal of the American Academy of Dermatology
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le mardi 28 janvier 2020
Doi : 10.1016/j.jaad.2019.08.045
accepted : 16 August 2019
BP180-specific IgG is associated with skin adverse events, therapy response, and overall survival in non-small cell lung cancer patients treated with checkpoint inhibitors
 

Omar Hasan Ali, MD a, b, David Bomze, MSc b, Sandra S. Ring, MSc b, Fiamma Berner, MSc b, Mirjam Fässler, MD b, c, Stefan Diem, MD b, d, e, Marie-Therese Abdou, MSc b, Christoph Hammers, MD f, g, h, Shirin Emtenani, MSc g, Anne Braun, MSc g, Antonio Cozzio, MD, PhD c, Bernhard Mani, PhD i, Wolfram Jochum, MD j, Enno Schmidt, MD, PhD f, g, h, Detlef Zillikens, MD f, g, h, Christian D. Sadik, MD, PhD f, g, h, Lukas Flatz, MD a, b, c, d,
a Department of Dermatology, University Hospital Zurich, Zurich, Switzerland 
b Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland 
c Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland 
d Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland 
e Department of Oncology and Hematology, Hospital of Grabs, Grabs, Switzerland 
f Department of Dermatology, University of Lübeck, Lübeck, Germany 
g Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany 
h Center for Research on Inflammation of the Skin (CRIS), Lübeck, Germany 
i Center of Laboratory Medicine, St. Gallen, Switzerland 
j Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland 

Correspondence to: Lukas Flatz, MD, Department of Dermatology, Kantonsspital St. Gallen, Rorschacher Str 95, CH-9007 St. Gallen, Switzerland.Department of DermatologyKantonsspital St. GallenRorschacher Str 95St. GallenCH-9007Switzerland
Abstract
Background

Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1(PD-L1) therapy frequently entails immune-related adverse events (irAEs), and biomarkers to predict irAEs are lacking. Although checkpoint inhibitors have been found to reinvigorate T cells, the relevance of autoantibodies remains elusive.

Objective

Our aim was to explore whether IgG autoantibodies directed against coexpressed antigens by tumor tissue and healthy skin correlate with skin irAEs and therapy outcome.

Methods

We measured skin-specific IgG via enzyme-linked immunosorbent assay in patients with non-small cell lung cancer (NSCLC) who received anti-PD1/PD-L1 treatment between July 2015 and September 2017 at the Kantonsspital St. Gallen. Sera were sampled at baseline and during therapy after 8 weeks.

Results

Analysis of publicly available tumor expression data revealed that NSCLC and skin coexpress BP180, BP230, and type VII collagen. A skin irAE developed in 16 of 40 recruited patients (40%). Only elevated anti-BP180 IgG at baseline significantly correlated with the development of skin irAEs (P  = .04), therapy response (P  = .01), and overall survival (P  = .04).

Limitations

The patients were recruited in a single tertiary care center.

Conclusions

Our data suggest that the level of anti-BP180 IgG of NSCLC patients at baseline is associated with better therapy response and overall survival and with a higher probability to develop skin irAEs during anti-PD1/PD-L1 treatment.

The full text of this article is available in PDF format.

Key words : anti-PD1, autoantibodies, immune checkpoint inhibitors, immune-related adverse events, non-small cell lung cancer, skin rash

Abbreviations used : BP, ELISA, ICIs, irAE, LP, NSCLC, OS, PD1, PD-L1



 Funding sources: This work was supported the Swiss National Science Foundation (PP00P3_157448) to Dr Flatz; the Deutsche Forschungsgemeinschaft (Clinical Research Unit 303 Pemphigoid Diseases) and the Excellence Cluster “Inflammation at Interfaces” to Drs Schmidt, Zillikens, and Sadik; and the Forschungsförderung of the Kantonsspital St. Gallen to Dr Flatz.
 Conflicts of interest: Dr Zillikens has received research and development grants from Euroimmun Inc, Lübeck, Germany, for development of novel diagnostic test systems for autoantibodies in autoimmune bullous diseases, and Dr Schmidt has scientific cooperation with Euroimmun Inc.
 Reprints not available from the authors.



© 2019  American Academy of Dermatology, Inc.@@#104156@@
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