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Five Japanese cases of antidesmoglein 1 antibody-positive and antidesmoglein 3 antibody-negative pemphigus with oral lesions

Authors

  • H. Koga,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • B. Ohyama,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • D. Tsuruta,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • N. Ishii,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • T. Hamada,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • T. Dainichi,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • Y. Natsuaki,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • R. Sogame,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • S. Fukuda,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • T. Karashima,

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • J. Tada,

    1. Section of Dermatology, Kagawa Prefectural Central Hospital, 5-4-16 Bancho, Takamatsu-shi, Kagawa 760-8558, Japan
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  • M. Yamashiro,

    1. Department of Dermatology, Ryukyu University School of Medicine, 207 Uehara Nishiharacho, Nakagamigun, Okinawa 903-0125, Japan
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  • H. Uezato,

    1. Department of Dermatology, Ryukyu University School of Medicine, 207 Uehara Nishiharacho, Nakagamigun, Okinawa 903-0125, Japan
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  • P. T. Chan,

    1. Social Hygiene Service, Department of Health, Cheung Sha Wan Dermatological Clinic, 3/F West Kowloon Health Centre, 303 Cheung Sha Wan Road, Kowloon, Hong Kong, China
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  • T. Hashimoto

    1. Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan
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  • Funding sources
    This study was supported by Grants-in-Aid for Scientific Research and Strategic Research Basis Formation Supporting Project from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Health and Labour Sciences Research Grants and grants for Research on Measures for Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan. The study was also supported by grants from the Uehara Memorial Foundation, Nakatomi Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Japan Lydia O’Leary Memorial Foundation, Cosmetology Research Foundation, Japanese Dermatological Association (Shiseido Award), Fukuoka Foundation for Sound Health, and Galderma K.K. (Galderma Award).

  • Conflicts of interest
    None declared.

  • H.K and B.O. are joint first authors.

Takashi Hashimoto.
E-mail: hashimot@med.kurume-u.ac.jp

Summary

Background  Oral mucosal lesions develop in pemphigus vulgaris, but not in pemphigus foliaceus. This clinical phenomenon is explained by the ‘desmoglein (Dsg) compensation theory’. Dsg3 and Dsg1 are major autoantigens for pemphigus vulgaris and pemphigus foliaceus, respectively. Dsg3 is overexpressed and Dsg1 is weakly expressed on the oral mucosa. Thus, on the oral mucosa, suppression of Dsg3 function by anti-Dsg3 autoantibodies is not compensated by weakly expressed Dsg1 in pemphigus vulgaris, while suppression of Dsg1 function by anti-Dsg1 autoantibodies is perfectly compensated by richly expressed Dsg3 in pemphigus foliaceus.

Objectives  We present five Japanese patients with pemphigus who deviate from this theory, i.e. all patients showed oral lesions (three also had cutaneous lesions) and reacted only with Dsg1, but not with Dsg3, by enzyme-linked immunosorbent assay.

Methods  To confirm whether the unique clinical phenotypes in our patients were due to a different immunological profile from that in classical pemphigus, we examined the reactivity of the patient sera by immunoprecipitation-immunoblotting analysis using five Dsg1/Dsg2 domain-swapped molecules.

Results  The sera of two patients who had only oral lesions tended to react with the extracellular (EC) 5 domain of Dsg1, the domain that is considered nonpathogenic in classical pemphigus foliaceus. Sera of three patients with mucocutaneous lesions reacted with EC1 domain or with both EC1 and EC2 domains of Dsg1, like classical pemphigus foliaceus.

Conclusions  These results indicate that antigenic diversity of anti-Dsg1 antibodies in these patients may cause the unique oral mucosal and cutaneous lesions, although further studies are required to elucidate the pathomechanisms.

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