Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

BMC Immunology

Research Article

Michael Hertl¹  Takashi Hashimoto²  Susanne Ganz³  Leena Bruckner-Tuderman⁴  Cassian Sitaru⁴  Emilia Licarete⁵  Martin J Recknagel⁶  Giovanni Di Zenzo⁷  Giovanna Zambruno⁷  Jonas Mudter⁸  Gheorghe Hundorfean⁸  Markus F Neurath⁸ 

[1] Department of Dermatology and Allergology, University of Marburg, Baldingerdstraße, 33043, Marburg, Germany;Department of Dermatology, Kurume University, 67 Asahimachi, 830-0011, Kurume Fukuoka, Japan;Department of Dermatology, University of Freiburg, Hauptstr. 7, 79104, Freiburg, Germany;Department of Dermatology, University of Freiburg, Hauptstr. 7, 79104, Freiburg, Germany;Centre for Biological Signalling Studies (bioss), University of Freiburg, Freiburg, Germany;Department of Dermatology, University of Freiburg, Hauptstr. 7, 79104, Freiburg, Germany;Department of Experimental Biology and Molecular Biology Center, Institute for Interdisciplinary Research on Bio-Nano-Sciences, Babes-Bolyai University Cluj-Napoca, Cluj-Napoca, Romania;Faculty of Biology, Genetics and Experimental Bioinformatics Group, University of Freiburg, Freiburg, Germany;Molecular and Cell Biology Laboratory, IDI-IRCCS, Rome, Italy;University of Erlangen-Nuremberg, Medical Clinic I, Erlangen, Ulmenweg 18, 91054, Erlangen, Germany;

关键词: Hinge Region;    Bullous Pemphigoid;    Epidermolysis Bullosa Acquisita;    Autoimmune Bullous Disease;    Autoimmune Blistering Disease;   

DOI  :  10.1186/1471-2172-13-16

 received in 2011-11-25, accepted in 2012-04-04,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAutoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA), but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors.MethodsBased on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50), Crohn's disease (CD, n = 50), ulcerative colitis (UC, n = 50), bullous pemphigoid (BP, n = 76), and pemphigus vulgaris (PV, n = 42) and healthy donors (n = 245).ResultsBy ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005), allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%), 2 CD (4%; 95% CI: 0%-9.43%), 8 UC (16%; 95% CI: 5.8%-26%), 2 BP (2.63%; 95% CI: 0%-6.23%), and 4 PV (9.52%; 95% CI: 0%-18.4%) patients as well as from 4 (1.63%; 95% CI: 0%-3.21%) healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen.ConclusionsUsing a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should prove a useful tool for clinical and translational research and should improve the routine diagnosis and disease monitoring in diseases associated with collagen VII-specific autoimmunity.

【 授权许可】

Unknown   
© Licarete et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.