The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases

BackgroundRecently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence...

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Autores principales: Hua Qian, Yohei Natsuaki, Hiroshi Koga, Tamihiro Kawakami, Chiharu Tateishi, Daisuke Tsuruta, Norito Ishii, Xiaoguang Li, Takashi Hashimoto
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spelling oai:doaj.org-article:9d093b45db3643eeaf5450e9133bbbcf2021-12-01T04:44:10ZThe Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases1664-322410.3389/fimmu.2021.771766https://doaj.org/article/9d093b45db3643eeaf5450e9133bbbcf2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.771766/fullhttps://doaj.org/toc/1664-3224BackgroundRecently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence and absence of antibodies to non-LM332 autoantigens. However, indirect immunofluorescence using 1M-NaCl-split normal human skin (ssIIF) is also valuable for diagnosis of anti-LM332-type MMP.MethodsIn this second study, we selected 133 anti-LM332-type MMP cases, which were diagnosed by our different inclusion criteria: (i) immunoglobulin G (IgG) deposition to basement membrane zone (BMZ) by direct immunofluorescence or IgG reactivity with dermal side of split skin by ssIIF, (ii) positivity for at least one of the three subunits of LM332 by immunoblotting of purified human LM332, and (iii) the presence of mucosal lesions. Clinical, histopathological, and immunological findings were summarized and analyzed statistically. Although these cases included the 55 previous cases, the more detailed study for larger scale of patients was conducted for further characterization.ResultsClinically, among the 133 patients, 89% and 43% patients had oral and ocular mucosal lesions, respectively, 71% had cutaneous lesions, and 17% had associated malignancies. Histopathologically, 93% patients showed subepidermal blisters. The sensitivities of ssIIF and direct immunofluorescence are similar but are significantly higher than indirect immunofluorescence using non-split human skin (both p < 0.001). In immunoblotting of purified LM332, patient IgG antibodies most frequently reacted with LMγ2 subunit (58%), followed by LMα3 (49%) and LMβ3 (36%). Thirty-four percent patients recognized additional non-LM332 autoantigens. Statistical analysis revealed that autoantibodies against non-LM332 autoantigens might stimulate the production of anti-LMγ2 antibodies.ConclusionsThis retrospective study further characterized in more detail the clinical and immunological features of 133 cases of anti-LM332-type MMP, in which the new diagnostic criteria without positive direct immunofluorescence reactivity were useful for the diagnosis. Higher frequency with anti-LMγ2 antibodies suggested more significant pathogenic role of this subunit. Additional autoantibodies to non-LM332 autoantigens detected in one-third of the patients may contribute to complexity in anti-LM332-type MMP, including the induction of anti-LMγ2 antibodies.Hua QianHua QianYohei NatsuakiHiroshi KogaTamihiro KawakamiChiharu TateishiDaisuke TsurutaDaisuke TsurutaNorito IshiiXiaoguang LiXiaoguang LiTakashi HashimotoTakashi HashimotoFrontiers Media S.A.articleanti-laminin-332-type mucous membrane pemphigoidimmunoblottingimmunofluorescencepathogenesisdiagnostic criteriaImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic anti-laminin-332-type mucous membrane pemphigoid
immunoblotting
immunofluorescence
pathogenesis
diagnostic criteria
Immunologic diseases. Allergy
RC581-607
spellingShingle anti-laminin-332-type mucous membrane pemphigoid
immunoblotting
immunofluorescence
pathogenesis
diagnostic criteria
Immunologic diseases. Allergy
RC581-607
Hua Qian
Hua Qian
Yohei Natsuaki
Hiroshi Koga
Tamihiro Kawakami
Chiharu Tateishi
Daisuke Tsuruta
Daisuke Tsuruta
Norito Ishii
Xiaoguang Li
Xiaoguang Li
Takashi Hashimoto
Takashi Hashimoto
The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases
description BackgroundRecently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence and absence of antibodies to non-LM332 autoantigens. However, indirect immunofluorescence using 1M-NaCl-split normal human skin (ssIIF) is also valuable for diagnosis of anti-LM332-type MMP.MethodsIn this second study, we selected 133 anti-LM332-type MMP cases, which were diagnosed by our different inclusion criteria: (i) immunoglobulin G (IgG) deposition to basement membrane zone (BMZ) by direct immunofluorescence or IgG reactivity with dermal side of split skin by ssIIF, (ii) positivity for at least one of the three subunits of LM332 by immunoblotting of purified human LM332, and (iii) the presence of mucosal lesions. Clinical, histopathological, and immunological findings were summarized and analyzed statistically. Although these cases included the 55 previous cases, the more detailed study for larger scale of patients was conducted for further characterization.ResultsClinically, among the 133 patients, 89% and 43% patients had oral and ocular mucosal lesions, respectively, 71% had cutaneous lesions, and 17% had associated malignancies. Histopathologically, 93% patients showed subepidermal blisters. The sensitivities of ssIIF and direct immunofluorescence are similar but are significantly higher than indirect immunofluorescence using non-split human skin (both p < 0.001). In immunoblotting of purified LM332, patient IgG antibodies most frequently reacted with LMγ2 subunit (58%), followed by LMα3 (49%) and LMβ3 (36%). Thirty-four percent patients recognized additional non-LM332 autoantigens. Statistical analysis revealed that autoantibodies against non-LM332 autoantigens might stimulate the production of anti-LMγ2 antibodies.ConclusionsThis retrospective study further characterized in more detail the clinical and immunological features of 133 cases of anti-LM332-type MMP, in which the new diagnostic criteria without positive direct immunofluorescence reactivity were useful for the diagnosis. Higher frequency with anti-LMγ2 antibodies suggested more significant pathogenic role of this subunit. Additional autoantibodies to non-LM332 autoantigens detected in one-third of the patients may contribute to complexity in anti-LM332-type MMP, including the induction of anti-LMγ2 antibodies.
format article
author Hua Qian
Hua Qian
Yohei Natsuaki
Hiroshi Koga
Tamihiro Kawakami
Chiharu Tateishi
Daisuke Tsuruta
Daisuke Tsuruta
Norito Ishii
Xiaoguang Li
Xiaoguang Li
Takashi Hashimoto
Takashi Hashimoto
author_facet Hua Qian
Hua Qian
Yohei Natsuaki
Hiroshi Koga
Tamihiro Kawakami
Chiharu Tateishi
Daisuke Tsuruta
Daisuke Tsuruta
Norito Ishii
Xiaoguang Li
Xiaoguang Li
Takashi Hashimoto
Takashi Hashimoto
author_sort Hua Qian
title The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases
title_short The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases
title_full The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases
title_fullStr The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases
title_full_unstemmed The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases
title_sort second study of clinical and immunological findings in anti-laminin 332-type mucous membrane pemphigoid examined at kurume university—diagnosis criteria suggested by summary of 133 cases
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/9d093b45db3643eeaf5450e9133bbbcf
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