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Pathogenicity of autoantibodies in anti-p200 pemphigoid.
PLoS One. 2012; 7(7):e41769.Plos

Abstract

Recently, the C-terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid and the disease was renamed as anti-laminin γ1 pemphigoid. However, the pathogenic relevance of these autoantibodies has not yet been demonstrated. Therefore, we employed an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation and dermal-epidermal separation (DES) using cryosections of human skin. We showed that anti-p200 pemphigoid sera (n = 7) induced DES in a time-dependent manner, in contrast to sera from healthy controls. Furthermore, laminin γ1-specific IgG and serum depleted from anti-laminin γ1 reactivity were generated using the recombinant C-terminus of laminin γ1 (LAMC1-term; amino acids 1364 to 1609). Interestingly, both fractions labeled the dermal-epidermal-junction (DEJ) by indirect immunofluorescence microscopy on human foreskin and recognized a 200 kDa protein by immunoblotting with dermal extract. Human and rabbit IgG against LAMC1-cterm failed to attract neutrophils at the DEJ and to induce DES. In contrast, patient serum depleted from LAMC1-cterm reactivity led to the same extent of DES as non-depleted IgG. Repeated injection of rabbit anti-murine LAMC1-cterm IgG into both neonatal and adult C57BL/6mice as well as repetitive immunization of various mouse strains with murine LAMC1-cterm failed to induce macro- and microscopic lesions. In all mice, circulating anti-LAMC1-cterm antibodies were present, but only in some mice, IgG deposits were seen at the DEJ. We conclude that autoantibodies in anti-p200 pemphigoid sera are pathogenic while pathogenicity is not mediated by autoantibodies against laminin γ1. Further studies are needed to identify the pathogenically relevant autoantigen in anti-p200 pemphigoid.

Authors+Show Affiliations

Department of Dermatology, University of Luebeck, Luebeck, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22911854

Citation

Vafia, Katerina, et al. "Pathogenicity of Autoantibodies in Anti-p200 Pemphigoid." PloS One, vol. 7, no. 7, 2012, pp. e41769.
Vafia K, Groth S, Beckmann T, et al. Pathogenicity of autoantibodies in anti-p200 pemphigoid. PLoS One. 2012;7(7):e41769.
Vafia, K., Groth, S., Beckmann, T., Hirose, M., Dworschak, J., Recke, A., Ludwig, R. J., Hashimoto, T., Zillikens, D., & Schmidt, E. (2012). Pathogenicity of autoantibodies in anti-p200 pemphigoid. PloS One, 7(7), e41769. https://doi.org/10.1371/journal.pone.0041769
Vafia K, et al. Pathogenicity of Autoantibodies in Anti-p200 Pemphigoid. PLoS One. 2012;7(7):e41769. PubMed PMID: 22911854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathogenicity of autoantibodies in anti-p200 pemphigoid. AU - Vafia,Katerina, AU - Groth,Stephanie, AU - Beckmann,Tina, AU - Hirose,Misa, AU - Dworschak,Jenny, AU - Recke,Andreas, AU - Ludwig,Ralf J, AU - Hashimoto,Takashi, AU - Zillikens,Detlef, AU - Schmidt,Enno, Y1 - 2012/07/24/ PY - 2012/01/31/received PY - 2012/06/28/accepted PY - 2012/8/23/entrez PY - 2012/8/23/pubmed PY - 2013/2/23/medline SP - e41769 EP - e41769 JF - PloS one JO - PLoS One VL - 7 IS - 7 N2 - Recently, the C-terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid and the disease was renamed as anti-laminin γ1 pemphigoid. However, the pathogenic relevance of these autoantibodies has not yet been demonstrated. Therefore, we employed an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation and dermal-epidermal separation (DES) using cryosections of human skin. We showed that anti-p200 pemphigoid sera (n = 7) induced DES in a time-dependent manner, in contrast to sera from healthy controls. Furthermore, laminin γ1-specific IgG and serum depleted from anti-laminin γ1 reactivity were generated using the recombinant C-terminus of laminin γ1 (LAMC1-term; amino acids 1364 to 1609). Interestingly, both fractions labeled the dermal-epidermal-junction (DEJ) by indirect immunofluorescence microscopy on human foreskin and recognized a 200 kDa protein by immunoblotting with dermal extract. Human and rabbit IgG against LAMC1-cterm failed to attract neutrophils at the DEJ and to induce DES. In contrast, patient serum depleted from LAMC1-cterm reactivity led to the same extent of DES as non-depleted IgG. Repeated injection of rabbit anti-murine LAMC1-cterm IgG into both neonatal and adult C57BL/6mice as well as repetitive immunization of various mouse strains with murine LAMC1-cterm failed to induce macro- and microscopic lesions. In all mice, circulating anti-LAMC1-cterm antibodies were present, but only in some mice, IgG deposits were seen at the DEJ. We conclude that autoantibodies in anti-p200 pemphigoid sera are pathogenic while pathogenicity is not mediated by autoantibodies against laminin γ1. Further studies are needed to identify the pathogenically relevant autoantigen in anti-p200 pemphigoid. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22911854/Pathogenicity_of_autoantibodies_in_anti_p200_pemphigoid_ L2 - https://dx.plos.org/10.1371/journal.pone.0041769 DB - PRIME DP - Unbound Medicine ER -