TY - JOUR
T1 - Integrin β4 is a major target antigen in pure ocular mucous membrane pemphigoid
AU - Li, Xiaoguang
AU - Qian, Hua
AU - Sogame, Ryosuke
AU - Hirako, Yoshiaki
AU - Tsuruta, Daisuke
AU - Ishii, Norito
AU - Koga, Hiroshi
AU - Tsuchisaka, Atsunari
AU - Jin, Zhexiong
AU - Tsubota, Kazuo
AU - Fukumoto, Akiko
AU - Sotozono, Chie
AU - Kinoshita, Shigeru
AU - Hashimoto, Takashi
N1 - Funding Information:
We gratefully appreciate Ms. Michiru Kubo for technical assistance, and Ms. Tomoko Tashima for secretarial work.We thank the patients for their participation. Financial support: This study was supported by Grants-in-Aid for Scientific Research (No. 20390308, 20591331, 21659271, 23591634, 23791298, 23791299, 23791300, 23791301, 24659534, 24591672, 24591640, 24791185), and Supported Program for the Strategic Research Foundation at Private Universities from the Ministry of Education, Culture, Sports, Science and Technology, and by "Research on Measures for Intractable Diseases" Project: matching fund subsidy (H23-028 to K. Iwatsuki, and H24-038 to T. Hashimoto) from the Ministry of Health, Labour and Welfare. The study was also supported by grants from the Kaibara Morikazu Medical Science Promotion Foundation, Ishibashi Foundation, Kanae Foundation for the Promotion of Medical Science, Takeda Science Foundation, Chuo Mitsui Trust and Banking Company, Limited, and Nakatomi Foundation.
Publisher Copyright:
© 2016 John Libbey Eurotext.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Background: Previous studies of ocular mucous membrane pemphigoid (OMMP) have identified several components of the basement membrane zone to be autoantigens, including integrin β4. However, there are no extensive or definitive reported studies that address this, particularly in pure OMMP. Objectives: To clarify the major autoantigens in pure OMMP. Materials and methods: In this study, we examined sera from 43 pure OMMP patients for both IgG and IgA antibodies using newly developed immunoblotting analyses with a hemidesmosome-rich fraction and various recombinant proteins of integrin α6β4, in addition to our routine immune-serological tests. Results: Using a hemidesmosome-rich fraction, sera from patients with pure OMMP demonstrated reactivity of IgG and/or IgA antibodies to integrin β4, BP180 and laminin- 332. The reactivity of pure OMMP sera to integrin β4 was further confirmed by immunoblotting using integrin β4 recombinant proteins. Using concentrated supernatant of HaCaT cells, only one serum sample showed positive IgG and IgA reactivity to LAD-1, the ectodomain of BP180. None of the pure OMMP sera reacted with any autoantigens on immunoblotting using normal human epidermal or dermal extracts, or purified human laminin-332. Conclusions: Integrin β4was considered to be the major and specific autoantigen for pureOMMP. The new methods established in this study are useful for detection of various autoantigens, particularly integrin β4.
AB - Background: Previous studies of ocular mucous membrane pemphigoid (OMMP) have identified several components of the basement membrane zone to be autoantigens, including integrin β4. However, there are no extensive or definitive reported studies that address this, particularly in pure OMMP. Objectives: To clarify the major autoantigens in pure OMMP. Materials and methods: In this study, we examined sera from 43 pure OMMP patients for both IgG and IgA antibodies using newly developed immunoblotting analyses with a hemidesmosome-rich fraction and various recombinant proteins of integrin α6β4, in addition to our routine immune-serological tests. Results: Using a hemidesmosome-rich fraction, sera from patients with pure OMMP demonstrated reactivity of IgG and/or IgA antibodies to integrin β4, BP180 and laminin- 332. The reactivity of pure OMMP sera to integrin β4 was further confirmed by immunoblotting using integrin β4 recombinant proteins. Using concentrated supernatant of HaCaT cells, only one serum sample showed positive IgG and IgA reactivity to LAD-1, the ectodomain of BP180. None of the pure OMMP sera reacted with any autoantigens on immunoblotting using normal human epidermal or dermal extracts, or purified human laminin-332. Conclusions: Integrin β4was considered to be the major and specific autoantigen for pureOMMP. The new methods established in this study are useful for detection of various autoantigens, particularly integrin β4.
KW - Autoantibody
KW - Autoantigen
KW - Hemidesmosome-rich fraction
KW - Integrin α6β4
KW - Pure ocular mucous membrane pemphigoid
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U2 - 10.1684/ejd.2016.2772
DO - 10.1684/ejd.2016.2772
M3 - Article
C2 - 27193492
AN - SCOPUS:85006166062
SN - 1167-1122
VL - 26
SP - 247
EP - 253
JO - European Journal of Dermatology
JF - European Journal of Dermatology
IS - 3
ER -