TY  - JOUR
A1  - Almanzar, Giovanni
A1  - Klein, Matthias
A1  - Schmalzing, Marc
A1  - Hilligardt, Deborah
A1  - El Hajj, Nady
A1  - Kneitz, Hermann
A1  - Wild, Vanessa
A1  - Rosenwald, Andreas
A1  - Benoit, Sandrine
A1  - Hamm, Henning
A1  - Tony, Hans-Peter
A1  - Haaf, Thomas
A1  - Goebeler, Matthias
A1  - Prelog, Martina
T1  - Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis
JF  - International Archives of Allergy and Immunology
N2  - Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.
KW  - methylation
KW  - systemic sclerosis
KW  - suppression
KW  - Tregs
KW  - Th17
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196577
SN  - 1018-2438
SN  - 1423-0097
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 171
IS  - 2
ER  - 
TY  - JOUR
A1  - Benoit, Sandrine
A1  - Scheurlen, Michael
A1  - Goebeler, Matthias
A1  - Stoevesandt, Johanna
T1  - Structured diagnostic approach and risk assessment in mucous membrane pemphigoid with oesophageal involvement
JF  - Acta Dermato-Venereologica
N2  - Oesophageal involvement in mucous membrane pemphigoid is considered rare, but it may be underdiagnosed. To assess the incidence of oesophageal involvement in a group of patients with newly diagnosed mucous membrane pemphigoid we retrospectively analysed the medical records of 30 consecutive patients with mucous membrane pemphigoid diagnosed between 2006 and 2016 at the Department of Dermatology, University Hospital Würzburg. Twenty-one patients (70%) reported symptoms indicative of oesophageal mucous membrane pemphigoid. Twelve patients (40%) underwent oesophagogastroduodenoscopy, and oesophageal pathology compatible with mucous membrane pemphigoid was endoscopically found in 9 cases (30%). In all patients indirect and direct immunofluorescence were performed. Patients with and without oesophageal involvement did not differ with regard to the results of indirect immunofluorescence on salt-split human skin and monkey oesophagus. Study results demonstrate the necessity of a standardized diagnostic work-up, including adequate tissue samples for direct immunofluorescence, to prevent underdiagnosis of oesophageal mucous membrane pemphigoid.
KW  - cicatricial pemphigoid
KW  - mucous membrane pemphigoid
KW  - oesophagogastroduodenoscopy
KW  - laminin 332
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176191
VL  - 98
ER  -