OBJECTIVES: A clinico-pathological study in diffuse systemic sclerosis (SSc) patients was performed to analyse whether the skin histological organization and the pro-fibrotic signals elicited by TGF-beta in fibroblasts vary according to the modified Rodnan skin score (mRSS). METHODS: Twenty-seven SSc patients underwent 45 skin biopsies with simultaneous measure of mRSS before or after treatment by immunosuppressive drugs, with or without autologous peripheral haematopoietic stem cell transplantation (HSCT). RESULTS: Double-blind optic microscopy analysis of the biopsies standard extracellular matrix stains allowed to define three histological subgroups: 6 with grade 1 weak fibrosis, 30 with grade 2 moderate fibrosis and 9 with grade 3 severe fibrosis. A significant (P < 0.0001) was identified between the grades of fibrosis and the mRSS. In skin fibroblast cultures, Smad3 phosphorylation levels, as well as mRNA steady-state levels of two transforming growth factor (TGF)-beta/Smad3 targets, COL1A2 and PAI-1, increased in parallel with the mRSS. When compared with pre-transplant values the degree of fibrosis observed after HSCT in the papillary and in the reticular dermis decreased in parallel with the fall in mRSS (n = 5 consecutive patients with repeated biopsies). CONCLUSIONS: The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT. The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease.
OBJECTIVES: A clinico-pathological study in diffuse systemic sclerosis (SSc) patients was performed to analyse whether the skin histological organization and the pro-fibrotic signals elicited by TGF-beta in fibroblasts vary according to the modified Rodnan skin score (mRSS). METHODS: Twenty-seven SSc patients underwent 45 skin biopsies with simultaneous measure of mRSS before or after treatment by immunosuppressive drugs, with or without autologous peripheral haematopoietic stem cell transplantation (HSCT). RESULTS: Double-blind optic microscopy analysis of the biopsies standard extracellular matrix stains allowed to define three histological subgroups: 6 with grade 1 weak fibrosis, 30 with grade 2 moderate fibrosis and 9 with grade 3 severe fibrosis. A significant (P < 0.0001) was identified between the grades of fibrosis and the mRSS. In skin fibroblast cultures, Smad3 phosphorylation levels, as well as mRNA steady-state levels of two transforming growth factor (TGF)-beta/Smad3 targets, COL1A2 and PAI-1, increased in parallel with the mRSS. When compared with pre-transplant values the degree of fibrosis observed after HSCT in the papillary and in the reticular dermis decreased in parallel with the fall in mRSS (n = 5 consecutive patients with repeated biopsies). CONCLUSIONS: The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT. The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease.
Authors: Richard A Nash; Peter A McSweeney; Leslie J Crofford; Muneer Abidi; Chien-Shing Chen; J David Godwin; Theodore A Gooley; Leona Holmberg; Gretchen Henstorf; C Fred LeMaistre; Maureen D Mayes; Kevin T McDonagh; Bernadette McLaughlin; Jerry A Molitor; J Lee Nelson; Howard Shulman; Rainer Storb; Federico Viganego; Mark H Wener; James R Seibold; Keith M Sullivan; Daniel E Furst Journal: Blood Date: 2007-04-23 Impact factor: 22.113
Authors: Howard M Shulman; Diana M Cardona; Joel K Greenson; Sangeeta Hingorani; Thomas Horn; Elisabeth Huber; Andreas Kreft; Thomas Longerich; Thomas Morton; David Myerson; Victor G Prieto; Avi Rosenberg; Nathaniel Treister; Kay Washington; Mirjana Ziemer; Steven Z Pavletic; Stephanie J Lee; Mary E D Flowers; Kirk R Schultz; Madan Jagasia; Paul J Martin; Georgia B Vogelsang; David E Kleiner Journal: Biol Blood Marrow Transplant Date: 2015-01-29 Impact factor: 5.742
Authors: Jun Wei; Asish K Ghosh; Jennifer L Sargent; Kazuhiro Komura; Minghua Wu; Qi-Quan Huang; Manu Jain; Michael L Whitfield; Carol Feghali-Bostwick; John Varga Journal: PLoS One Date: 2010-11-02 Impact factor: 3.240