T Cell participation in autoreactivity to NC16a epitopes in Bullous Pemphigoid

Wendy J Pickford, Venkat Gudi, Anne M Haggart, Barry J Lewis, Richard Herriot, Robert N Barker, Anthony Ormerod

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Bullous pemphigoid is a blistering skin disease characterized by autoantibodies against the NC16a domain of bullous pemphigoid 180. This study was performed to characterize and map the fine specifity of T cell responses to NC16a. PBMC from a total of 28 bullous pemphigoid patients and 14 matched controls were tested for proliferative and cytokine responses to recombinant NC16a and a complete panel of 21 overlapping peptides spanning this region of BP180. Proliferative responses to NC16A and the peptide panel in the patients with active disease were similar in frequency and magnitude to those in healthy donors, and included late responses typical of naive cells in about 60% of each group. IL-4 responses were slightly stronger for 6 peptides, and significantly stronger to Nc16a, in patients than controls. Factor analysis identified factors that separate responses to the peptide panel discretely into IL-4(Th2 pattern), IFNγ(Th1 pattern) and IL-10 or TGFβ(Treg pattern). Factors segregating IL-10 versus IFNγ were predicted by active blistering or remission, and TGFβ or IL-10 versus IFNγ by age. Finally, we confirmed a significant upregulation of IgE responses to BP180 in the patients with pemphigoid. This shows the complexity of T cell phenotype and fine autoreactive specificity in responses to NC16A, in patients and normal controls. Important disease associated factors determine the balance of cytokine responses. Of these, specific IL-4 and IgE responses show the strongest associations with pemphigoid, pointing to an important contribution by Th2 cytokines to pathogenesis.

Original languageEnglish
Pages (from-to)189-200
Number of pages12
JournalClinical and Experimental Immunology
Volume180
Issue number2
Early online date14 Apr 2015
DOIs
Publication statusPublished - May 2015

Fingerprint

Bullous Pemphigoid
Epitopes
T-Lymphocytes
Interleukin-4
Interleukin-10
Peptides
Cytokines
Immunoglobulin E
Skin Diseases
Autoantibodies
Statistical Factor Analysis
Up-Regulation
Tissue Donors
Phenotype

Keywords

  • autoimmunity
  • cytokines
  • Th1/Th2
  • regulatory T cells

Cite this

T Cell participation in autoreactivity to NC16a epitopes in Bullous Pemphigoid. / Pickford, Wendy J; Gudi, Venkat; Haggart, Anne M; Lewis, Barry J; Herriot, Richard; Barker, Robert N; Ormerod, Anthony.

In: Clinical and Experimental Immunology, Vol. 180, No. 2, 05.2015, p. 189-200.

Research output: Contribution to journalArticle

Pickford, Wendy J ; Gudi, Venkat ; Haggart, Anne M ; Lewis, Barry J ; Herriot, Richard ; Barker, Robert N ; Ormerod, Anthony. / T Cell participation in autoreactivity to NC16a epitopes in Bullous Pemphigoid. In: Clinical and Experimental Immunology. 2015 ; Vol. 180, No. 2. pp. 189-200.
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abstract = "Bullous pemphigoid is a blistering skin disease characterized by autoantibodies against the NC16a domain of bullous pemphigoid 180. This study was performed to characterize and map the fine specifity of T cell responses to NC16a. PBMC from a total of 28 bullous pemphigoid patients and 14 matched controls were tested for proliferative and cytokine responses to recombinant NC16a and a complete panel of 21 overlapping peptides spanning this region of BP180. Proliferative responses to NC16A and the peptide panel in the patients with active disease were similar in frequency and magnitude to those in healthy donors, and included late responses typical of naive cells in about 60{\%} of each group. IL-4 responses were slightly stronger for 6 peptides, and significantly stronger to Nc16a, in patients than controls. Factor analysis identified factors that separate responses to the peptide panel discretely into IL-4(Th2 pattern), IFNγ(Th1 pattern) and IL-10 or TGFβ(Treg pattern). Factors segregating IL-10 versus IFNγ were predicted by active blistering or remission, and TGFβ or IL-10 versus IFNγ by age. Finally, we confirmed a significant upregulation of IgE responses to BP180 in the patients with pemphigoid. This shows the complexity of T cell phenotype and fine autoreactive specificity in responses to NC16A, in patients and normal controls. Important disease associated factors determine the balance of cytokine responses. Of these, specific IL-4 and IgE responses show the strongest associations with pemphigoid, pointing to an important contribution by Th2 cytokines to pathogenesis.",
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AU - Lewis, Barry J

AU - Herriot, Richard

AU - Barker, Robert N

AU - Ormerod, Anthony

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AB - Bullous pemphigoid is a blistering skin disease characterized by autoantibodies against the NC16a domain of bullous pemphigoid 180. This study was performed to characterize and map the fine specifity of T cell responses to NC16a. PBMC from a total of 28 bullous pemphigoid patients and 14 matched controls were tested for proliferative and cytokine responses to recombinant NC16a and a complete panel of 21 overlapping peptides spanning this region of BP180. Proliferative responses to NC16A and the peptide panel in the patients with active disease were similar in frequency and magnitude to those in healthy donors, and included late responses typical of naive cells in about 60% of each group. IL-4 responses were slightly stronger for 6 peptides, and significantly stronger to Nc16a, in patients than controls. Factor analysis identified factors that separate responses to the peptide panel discretely into IL-4(Th2 pattern), IFNγ(Th1 pattern) and IL-10 or TGFβ(Treg pattern). Factors segregating IL-10 versus IFNγ were predicted by active blistering or remission, and TGFβ or IL-10 versus IFNγ by age. Finally, we confirmed a significant upregulation of IgE responses to BP180 in the patients with pemphigoid. This shows the complexity of T cell phenotype and fine autoreactive specificity in responses to NC16A, in patients and normal controls. Important disease associated factors determine the balance of cytokine responses. Of these, specific IL-4 and IgE responses show the strongest associations with pemphigoid, pointing to an important contribution by Th2 cytokines to pathogenesis.

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