Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA1*05:05 and -DRB1*07:01, in Germans

Christian Schwarm; Damian Gola; Maike M Holtsche; Anabelle Dieterich; Anita Bhandari; Miriam Freitag; Peter Nürnberg; Mohammad Toliat; Wolfgang Lieb; Michael Wittig; André Franke; Margitta Worm; Michael Sticherling; Jan Ehrchen; Claudia Günther; Regine Gläser; Wiebke K Peitsch; Miklós Sárdy; Rüdiger Eming; Michael Hertl; Sandrine Benoit; Matthias Goebeler; Claudia Pföhler; Manfred Kunz; Alexander Kreuter; Nina van Beek; Jeanette Erdmann; Hauke Busch; Detlef Zillikens; Christian D Sadik; Misa Hirose; Inke R König; Enno Schmidt; Saleh M Ibrahim; German AIBD Study Group

doi:10.1186/s13023-021-01863-9

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA105:05 and -DRB107:01, in Germans

Orphanet J Rare Dis. 2021 May 19;16(1):228. doi: 10.1186/s13023-021-01863-9.

Authors

Christian Schwarm^{1

2}, Damian Gola^{2

3}, Maike M Holtsche⁴, Anabelle Dieterich⁴, Anita Bhandari^{2

5}, Miriam Freitag^{1

2}, Peter Nürnberg⁶, Mohammad Toliat⁶, Wolfgang Lieb⁷, Michael Wittig⁸, André Franke⁸, Margitta Worm⁹, Michael Sticherling¹⁰, Jan Ehrchen¹¹, Claudia Günther¹², Regine Gläser¹³, Wiebke K Peitsch¹⁴, Miklós Sárdy^{15

16}, Rüdiger Eming¹⁷, Michael Hertl¹⁷, Sandrine Benoit¹⁸, Matthias Goebeler¹⁸, Claudia Pföhler¹⁹, Manfred Kunz²⁰, Alexander Kreuter²¹, Nina van Beek^{2

4}, Jeanette Erdmann^{2

5}, Hauke Busch^{1

2}, Detlef Zillikens^{2

4}, Christian D Sadik^{2

4}, Misa Hirose^{1

2}, Inke R König^{2

3}, Enno Schmidt^#^{1

2

4}, Saleh M Ibrahim^#^{22

23

24}; German AIBD Study Group

Affiliations

¹ Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
² CRIS, Center for Research On Inflammation of the Skin, University of Lübeck, Lübeck, Germany.
³ Institute of Medical Biometry and Statistics, University of Lübeck, University Clinic Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
⁴ Department of Dermatology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
⁵ Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
⁶ Cologne Center for Genomics, University of Cologne, Cologne, Germany.
⁷ Institute of Epidemiology and Popgen Biobank, Christian Albrechts-University of Kiel, Kiel, Germany.
⁸ Institute of Clinical Molecular Biology, Christian Albrechts-University of Kiel, Kiel, Germany.
⁹ Allegologie Und Immunologie, Klinik Für Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁰ Department of Dermatology, University Hospital Erlangen, Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
¹¹ Department of Dermatology, University of Münster, Münster, Germany.
¹² Department of Dermatology, University Hospital Dresden, Dresden, Germany.
¹³ University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
¹⁴ Department of Dermatology and Phlebology, Vivantes Klinikum Im Friedrichshain, Berlin, Germany.
¹⁵ Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary.
¹⁶ Department of Dermatology and Allergology, University Hospital, LMU Munich, Munich, Germany.
¹⁷ Department of Dermatology and Allergology, Philipps-Universität Marburg, Marburg, Germany.
¹⁸ Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.
¹⁹ Department of Dermatology, Saarland University Medical Center, Homburg/Saar, Germany.
²⁰ Department of Dermatology, Venereology and Allergology, Leipzig University Medical Center, Leipzig, Germany.
²¹ Department of Dermatology, Venerology and Allergology, Helios St. Elisabeth Hospital Oberhausen, University Witten/Herdecke, Oberhausen, Germany.
²² Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany. saleh.ibrahim@uksh.de.
²³ CRIS, Center for Research On Inflammation of the Skin, University of Lübeck, Lübeck, Germany. saleh.ibrahim@uksh.de.
²⁴ College of Medicine and Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE. saleh.ibrahim@uksh.de.

^# Contributed equally.

Abstract

Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease characterized by autoimmunity against the hemidesmosomal proteins BP180, type XVII collagen, and BP230. To elucidate the genetic basis of susceptibility to BP, we performed the first genome-wide association study (GWAS) in Germans. This GWAS was combined with HLA locus targeted sequencing in an additional independent BP cohort. The strongest association with BP in Germans tested in this study was observed in the two HLA loci, HLA-DQA1*05:05 and HLA-DRB1*07:01. Further studies with increased sample sizes and complex studies integrating multiple pathogenic drivers will be conducted.

Keywords: Autoimmune blistering skin diseases; Bullous pemphigoid; GWAS; Germans; HLA.

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Autoantibodies
Autoantigens
Genome-Wide Association Study
Germany
HLA-DQ alpha-Chains / genetics*
HLA-DRB1 Chains / genetics*
Humans
Non-Fibrillar Collagens
Pemphigoid, Bullous* / genetics

Substances

Autoantibodies
Autoantigens
HLA-DQ alpha-Chains
HLA-DQA1 antigen
HLA-DRB1 Chains
Non-Fibrillar Collagens