S Goletz1, C Probst2, L Komorowski2, W Schlumberger2, K Fechner2, N van Beek1, M M Holtsche1, A Recke3, K B Yancey4, T Hashimoto5, F Antonicelli6, G Di Zenzo7, D Zillikens3, W Stöcker2, E Schmidt1,3. 1. Lübeck Institute for Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany. 2. Institute of Experimental Immunology, EUROIMMUN AG, Lübeck, Germany. 3. Department of Dermatology, University of Lübeck, Lübeck, Germany. 4. Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A. 5. Department of Dermatology, Kurume University School of Medicine, Kurume, Japan. 6. Department of Dermatology, University of Reims, Reims, France. 7. Molecular and Cell Biology Laboratory, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Rome, Italy.
Abstract
BACKGROUND: Antilaminin 332 mucous membrane pemphigoid (MMP) is an autoimmune subepidermal blistering disease with predominant mucosal involvement and autoantibodies against laminin 332. Malignancies have been associated with this disease; however, no standardized detection system for antilaminin 332 serum antibodies is widely available. OBJECTIVES: Development of a sensitive and specific assay for the detection of antilaminin 332 antibodies. METHODS: An indirect immunofluorescence (IF) assay using recombinant laminin 332 was developed and probed with a large number of antilaminin 332 MMP patient sera (n = 93), as well as sera from patients with antilaminin 332-negative MMP (n = 153), bullous pemphigoid (n = 20), pemphigus vulgaris (n = 20) and noninflammatory dermatoses (n = 22), and healthy blood donors (n = 100). RESULTS: In the novel IF assay, sensitivities with the laminin 332 heterotrimer and the individual α3, β3 and γ2 chains were 77%, 43%, 41% and 13%, respectively, with specificities of 100% for each substrate. The sensitivity for the heterotrimer increased when an anti-IgG4 enriched antitotal IgG conjugate was applied. Antilaminin 332 reactivity paralleled disease activity and was associated with malignancies in 25% of patients with antilaminin 332 MMP. CONCLUSIONS: The novel IF-based assay will facilitate the serological diagnosis of antilaminin 332 MMP and may help to identify patients at risk of a malignancy.
BACKGROUND:Antilaminin 332 mucous membrane pemphigoid (MMP) is an autoimmune subepidermal blistering disease with predominant mucosal involvement and autoantibodies against laminin 332. Malignancies have been associated with this disease; however, no standardized detection system for antilaminin 332 serum antibodies is widely available. OBJECTIVES: Development of a sensitive and specific assay for the detection of antilaminin 332 antibodies. METHODS: An indirect immunofluorescence (IF) assay using recombinant laminin 332 was developed and probed with a large number of antilaminin 332 MMP patient sera (n = 93), as well as sera from patients with antilaminin 332-negative MMP (n = 153), bullous pemphigoid (n = 20), pemphigus vulgaris (n = 20) and noninflammatory dermatoses (n = 22), and healthy blood donors (n = 100). RESULTS: In the novel IF assay, sensitivities with the laminin 332 heterotrimer and the individual α3, β3 and γ2 chains were 77%, 43%, 41% and 13%, respectively, with specificities of 100% for each substrate. The sensitivity for the heterotrimer increased when an anti-IgG4 enriched antitotal IgG conjugate was applied. Antilaminin 332 reactivity paralleled disease activity and was associated with malignancies in 25% of patients with antilaminin 332 MMP. CONCLUSIONS: The novel IF-based assay will facilitate the serological diagnosis of antilaminin 332 MMP and may help to identify patients at risk of a malignancy.
Authors: Hideyuki Ujiie; David Rosmarin; Michael P Schön; Sonja Ständer; Katharina Boch; Martin Metz; Marcus Maurer; Diamant Thaci; Enno Schmidt; Connor Cole; Kyle T Amber; Dario Didona; Michael Hertl; Andreas Recke; Hanna Graßhoff; Alexander Hackel; Anja Schumann; Gabriela Riemekasten; Katja Bieber; Gant Sprow; Joshua Dan; Detlef Zillikens; Tanya Sezin; Angela M Christiano; Kerstin Wolk; Robert Sabat; Khalaf Kridin; Victoria P Werth; Ralf J Ludwig Journal: Front Med (Lausanne) Date: 2022-06-09
Authors: Sandra Saschenbrecker; Ingolf Karl; Lars Komorowski; Christian Probst; Cornelia Dähnrich; Kai Fechner; Winfried Stöcker; Wolfgang Schlumberger Journal: Front Immunol Date: 2019-08-20 Impact factor: 7.561
Authors: H Rashid; A Lamberts; L Borradori; S Alberti-Violetti; R J Barry; M Caproni; B Carey; M Carrozzo; F Caux; G Cianchini; A Corrà; G F H Diercks; F G Dikkers; G Di Zenzo; C Feliciani; G Geerling; G Genovese; M Hertl; P Joly; A V Marzano; J M Meijer; V Mercadante; D F Murrell; M Ormond; H H Pas; A Patsatsi; C Prost; S Rauz; B D van Rhijn; M Roth; E Schmidt; J Setterfield; G Zambruno; D Zillikens; B Horváth Journal: J Eur Acad Dermatol Venereol Date: 2021-07-10 Impact factor: 6.166