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J Am Acad Dermatol. 2019 Aug 23. pii: S0190-9622(19)32650-7. doi: 10.1016/j.jaad.2019.08.045. [Epub ahead of print]

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.

Author information

1
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
2
Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
3
Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
4
Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Oncology and Hematology, Hospital of Grabs, Grabs, Switzerland.
5
Department of Dermatology, University of Lubeck, Lubeck, Germany; Lübeck Institute of Experimental Dermatology, University of Lubeck, Lubeck, Germany; Center for Research on Inflammation of the Skin (CRIS), Lubeck, Germany.
6
Lübeck Institute of Experimental Dermatology, University of Lubeck, Lubeck, Germany.
7
Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
8
Center of Laboratory Medicine, St. Gallen, Switzerland.
9
Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
10
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland. Electronic address: lukas.flatz@kssg.ch.

Abstract

BACKGROUND:

Anti-PD1/PD-L1 therapy frequently entails immune-related adverse events (irAEs) and biomarkers to predict irAEs are lacking. While checkpoint inhibitors have been found to re-invigorate T-cells, the relevance of autoantibodies remains elusive.

OBJECTIVE:

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

METHODS:

We measured skin-specific IgG via ELISA in non-small cell lung cancer (NSCLC) patients, 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 co-express BP180, BP230 and type VII collagen. Of 40 recruited patients, 16 (40%) developed a skin irAE. 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, overall survival and a higher probability to develop skin irAEs during anti-PD1/PD-L1 treatment.

KEYWORDS:

anti-PD1; autoantibodies; immune checkpoint inhibitors; immune-related adverse events; non-small cell lung cancer; skin rash

PMID:
31449902
DOI:
10.1016/j.jaad.2019.08.045
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