Pathogenicity of autoantibodies in anti-p200 pemphigoid.
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 autoanti...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22911854/?tool=EBI |
| _version_ | 1818722983748829184 |
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| author | Katerina Vafia Stephanie Groth Tina Beckmann Misa Hirose Jenny Dworschak Andreas Recke Ralf J Ludwig Takashi Hashimoto Detlef Zillikens Enno Schmidt |
| author_facet | Katerina Vafia Stephanie Groth Tina Beckmann Misa Hirose Jenny Dworschak Andreas Recke Ralf J Ludwig Takashi Hashimoto Detlef Zillikens Enno Schmidt |
| author_sort | Katerina Vafia |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-43a9fd71d5514725b2cbad679e1bc0e4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T21:03:18Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-43a9fd71d5514725b2cbad679e1bc0e42022-12-21T21:32:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4176910.1371/journal.pone.0041769Pathogenicity of autoantibodies in anti-p200 pemphigoid.Katerina VafiaStephanie GrothTina BeckmannMisa HiroseJenny DworschakAndreas ReckeRalf J LudwigTakashi HashimotoDetlef ZillikensEnno SchmidtRecently, 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22911854/?tool=EBI |
| spellingShingle | Katerina Vafia Stephanie Groth Tina Beckmann Misa Hirose Jenny Dworschak Andreas Recke Ralf J Ludwig Takashi Hashimoto Detlef Zillikens Enno Schmidt Pathogenicity of autoantibodies in anti-p200 pemphigoid. PLoS ONE |
| title | Pathogenicity of autoantibodies in anti-p200 pemphigoid. |
| title_full | Pathogenicity of autoantibodies in anti-p200 pemphigoid. |
| title_fullStr | Pathogenicity of autoantibodies in anti-p200 pemphigoid. |
| title_full_unstemmed | Pathogenicity of autoantibodies in anti-p200 pemphigoid. |
| title_short | Pathogenicity of autoantibodies in anti-p200 pemphigoid. |
| title_sort | pathogenicity of autoantibodies in anti p200 pemphigoid |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22911854/?tool=EBI |
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