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Multicenter prospective study on multivariant diagnostics of autoimmune bullous dermatoses using the BIOCHIP technology - 10/10/20

Doi : 10.1016/j.jaad.2020.01.049 
Nina van Beek, MD a, Stine Krüger, MD a, Tarek Fuhrmann, MD a, Susanne Lemcke, PhD b, Stephanie Goletz, PhD b, Christian Probst, PhD c, Lars Komorowski, PhD c, Giovanni Di Zenzo, PhD d, Marian Dmochowski, MD e, Kossara Drenovska, MD, PhD f, Michael Horn, PhD g, Hana Jedlickova, MD h, Cezary Kowalewski, MD, PhD i, Ljiljana Medenica, MD, PhD j, Dedee Murrell, MD k, Aikaterini Patsatsi, MD l, Shamir Geller, MD m, Soner Uzun, MD n, Snejina Vassileva, MD, PhD f, Xuejun Zhu, MD o, Kai Fechner, PhD c, Detlef Zillikens, MD a, Winfried Stöcker, MD c, Enno Schmidt, MD, PhD a, b, ⁎ , Kristin Rentzsch c
a Department of Dermatology, University of Lübeck, Lübeck, Germany 
b Lübeck Institute of Experimental Dermatology, Lübeck, Germany 
c Institute of Experimental Immunology, EUROIMMUN AG, Lübeck, Germany 
d Molecular and Cell Biology Laboratory, IDI-IRCCS, Rome, Italy 
e Department of Dermatology, Poznan University of Medical Sciences, Poznan, Poland 
f Department of Dermatology and Venereology, Sofia University of Medicine, Sofia, Bulgaria 
g University Institute of Clinical Chemistry and Center of Laboratory Medicine, Bern, Switzerland 
h Department of Dermatology, St. Anna University Hospital, Brno, Czech Republic 
i Department of Dermatology and Immunodermatology, Medical University of Warsaw, Warsaw, Poland 
j Department of Dermatology, School of Medicine, University of Belgrade, Belgrade, Serbia 
k St. George Hospital, University of New South Wales School of Medicine, Sydney, Australia 
l 2nd Dermatology Department, Aristotle University School of Medicine, Papageorgiou General Hospital, Thessaloniki, Greece 
m Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel 
n Department of Dermatology, Faculty of Medicine, Akdeniz University, Antalya, Turkey 
o Department of Dermatology, Beijing University First Hospital, Beijing, China 

∗Reprint requests: Enno Schmidt, MD, PhD, Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany.Department of DermatologyUniversity of LübeckRatzeburger Allee 160LübeckD-23538Germany

Abstract

Background

The current standard in the serologic diagnosis of autoimmune bullous diseases (AIBD) is a multistep procedure sequentially applying different assays. In contrast, the BIOCHIP Mosaic technology combines multiple substrates for parallel analysis by indirect immunofluorescence.

Methods

Sera from 749 consecutive, prospectively recruited patients with direct immunofluorescence–positive AIBD from 13 international study centers were analyzed independently and blinded by using (1) a BIOCHIP Mosaic including primate esophagus, salt-split skin, rat bladder, monkey liver, monkey liver with serosa, recombinant BP180 NC16A, and gliadin GAF3X, as well as HEK293 cells expressing recombinant desmoglein 1, desmoglein 3, type VII collagen, and BP230 C-terminus and (2) the conventional multistep approach of the Department of Dermatology, University of Lübeck.

Results

In 731 of 749 sera (97.6%), specific autoantibodies could be detected with the BIOCHIP Mosaic, similar to the conventional procedure (725 cases, 96.8%). The Cohen κ for both serologic approaches ranged from 0.84 to 1.00. In 6.5% of sera, differences between the 2 approaches occurred and were mainly attributed to autoantigen fragments not present on the BIOCHIP Mosaic.

Limitations

Laminin 332 and laminin γ1 are not represented on the BIOCHIP Mosaic.

Conclusions

The BIOCHIP Mosaic is a standardized time- and serum-saving approach that further facilitates the serologic diagnosis of AIBD.

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Graphical abstract




El texto completo de este artículo está disponible en PDF.

Key words : autoimmune bullous diseases, biochip, immunofluorescence, pemphigoid, pemphigus

Abbreviations used : Aab, AIBD, BP, Dsg, EBA, IF


Esquema


 Mrs Krüger and Mr Fuhrmann contributed equally to this article. Drs Schmidt and Rentzsch contributed equally to this article.
 Funding sources: Supported by Deutsche Forschungsgemeinschaft through the Research Training Group 1727 Modulation of Autoimmunity (to Mrs Krüger and Mr Fuhrmann), the Clinical Research Unit 303 Pemphigoid Diseases (to Drs van Beek, Zillikens, and Schmidt), the Schleswig-Holstein Cluster of Excellence Inflammation at Interfaces (EXC 306/2 to Drs Zillikens and Schmidt), and a research grant of EUROIMMUN, Lübeck, Germany, including free provision of BIOCHIP Mosaics (to Dr Schmidt).
 Disclosure: Drs Probst, Komorowski, Fechner, and Rentzsch are employees of and Dr Stöcker is a board member of EUROIMMUN. Drs Zillikens and Schmidt have a scientific cooperation with EUROIMMUN. Dr van Beek, Mrs Krüger, Mr Fuhrmann, and Drs Lemcke, Goletz, Di Zenzo, Dmochowski, Drenovska, Horn, Jedlickova, Kowalewski, Medenica, Murrell, Patsatsi, Geller, Uzun, Vassileva, and Zhu have no conflicts of interest to declare.
 IRB approval status: Reviewed and approved by the ethics committee of the University of Lübeck (#11-078).


© 2020  American Academy of Dermatology, Inc.. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 83 - N° 5

P. 1315-1322 - novembre 2020 Regresar al número
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