{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:01:48Z","timestamp":1773248508376,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bullous pemphigoid (BP), an autoimmune subepidermal blistering disease, shows tense blisters associated with urticarial erythema. Tissue\u2010bound Immunoglobulin G (IgG) at the basement membrane zone (BMZ) detected by direct immunofluorescence (DIF) is strong evidence for a diagnosis of BP. The sensitivity of DIF is higher in complement component 3 (C3) than in IgG, but the reason for this different sensitivity is not fully understood. In this study, we performed several ex\u00a0vivo studies to investigate the possible mechanism of IgG negativity and C3 positivity at the BMZ by DIF in some BP cases. First, sera from BP patients showing IgG negativity by DIF were found to clearly react to the BMZ in their own DIF skin samples. Next, indirect immunofluorescence (IIF) was performed using sera diluted with different pH phosphate\u2010buffered saline (PBS), pH\u20097.4, 6.0, and 3.0. Patients' sera diluted with pH\u20097.4 PBS showed linear staining at the BMZ, but sera diluted with pH\u20096.0 PBS and pH\u20093.0 PBS showed lower fluorescence intensities. Finally, sections of skin from BP patients were pre\u2010incubated with different pH PBS (pH\u20093.0, 6.0, and 7.4), followed by staining with anti\u2010human IgG and C3. The fluorescence intensities were notably lower for IgG and C3 that had been pre\u2010incubated with pH\u20093.0 PBS and pH\u20096.0 PBS than for IgG and C3 that had been pre\u2010incubated with pH\u20097.4 PBS. These results suggest that a low pH condition hinders the binding of autoantibodies to the BMZ, that is, the drop in tissue pH induced by inflammation inhibits autoantibodies from depositing at the BMZ. Furthermore, the drop in tissue pH causes tissue\u2010bound autoantibodies to detach from the BMZ. Complement fragments are activated not only on IgG but also on the cell surface of cells close to IgG during complement activation. IgG may detach from the BMZ under low pH condition induced by inflammation, but some complement fragments remain at the BMZ. These phenomena may help to explain why C3 is more sensitive than IgG when DIF is used to diagnose BP.<\/jats:p>","DOI":"10.1111\/1346-8138.17175","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T11:31:14Z","timestamp":1710415874000},"page":"643-648","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Low <scp>pH<\/scp> condition impairs <scp>BP\u2010IgG<\/scp> binding to the basement membrane zone"],"prefix":"10.1111","volume":"51","author":[{"given":"Dongjun","family":"Im","sequence":"first","affiliation":[{"name":"Department of Dermatology Gifu University Graduate School of Medicine  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Dermatology Gifu University Graduate School of Medicine  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Niwa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Gifu University Graduate School of Medicine  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayoko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Dermatology Gifu University Graduate School of Medicine  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Dermatology Gifu University Graduate School of Medicine  Gifu 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