Patients belonged to three main entities: rheumatoid arthritis (RA, <i>n</i> = 32), collagen diseases (CD, <i>n</i> = 56) also including systemic sclerosis (SSc, <i>n</i> = 11), and other autoimmune diseases (<i>n</i> = 12). sICAM-1 was similar among groups. sELAM-1 was elevated by 1.9-fold in only in SSc. sVCAM-1 was elevated by 3.1-fold in RA and by 3.3-fold in CD and in other autoimmune diseases by 3.4-fold.
There were significant associations between the genotype and allele frequencies of UTS2 gene Thr21Met polymorphism and cases with diffuse or limited SSc, systemic or lung involvement, finger flexion deformity, pitting scars at the fingertips, positive anticentromere, or positive antitopoisomerase 1 antibody groups.
Three SSU processome components and their related human diseases will be explored in this review: hUTP4/Cirhin, implicated in North American Indian childhood cirrhosis (NAIC); UTP14, implicated in infertility, ovarian cancer, and scleroderma; and EMG1, implicated in Bowen-Conradi syndrome (BCS).
In these studies, we define Ufd2 (a novel E4 polyubiquitylating enzyme) as a new autoantigen in scleroderma, and show that it regulates chromosome condensation and separation during mitosis in human cells.
In these studies, we define Ufd2 (a novel E4 polyubiquitylating enzyme) as a new autoantigen in scleroderma, and show that it regulates chromosome condensation and separation during mitosis in human cells.
Interestingly, dependence and allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants.
These results demonstrate that the transplantation of Trx-1-overexpressing BMSCs restored normal skin tissue in a mouse model of bleomycin-induced SSc, highlighting the therapeutic potential of engineered BMSCs for treating SSc.
CD31+CD102+ ECs isolated from SSc lungs expressed high levels of mesenchymal cell-specific genes (type I collagen, type III collagen, and fibronectin), EC-specific genes (type IV collagen and VE-cadherin), profibrotic genes (transforming growth factor β1 and connective tissue growth factor), and genes encoding EndoMT-related transcription factors (TWIST1 and SNAI2).
In the RHC subgroup (n=28), mean (m)PAP and pulmonary vascular resistance at 50 W increased significantly (p=0.02 and p=0.002, respectively), but resting mPAP was unchanged.Scleroderma patients without PAH develop a mild but significant deterioration of pulmonary exercise haemodynamics and exercise capacity over a 4-year follow-up period, indicating a progression of pulmonary vascular disease.
Using a human autoimmune scleroderma serum that identifies a chromosomal protein in human cells and Drosophila embryos, we cloned the corresponding Drosophila gene that encodes the homologue of vertebrate titin based on protein size, sequence similarity, developmental expression and subcellular localization.
Expression of TNFRSF12A (the TWEAK receptor/fibroblast growth factor-inducible 14) was elevated in skin from patients with fibroproliferative SSc and the skin of Tsk2/+ mice.
The high frequency of anti-Scl70 and anti-centromere autoantibodies indicates that Tsk2/+ mice display some humoral immune alterations which are similar to those found in patients with SSc.
The TSK1 mouse model of SSc bears an in-frame duplication of the Fibrillin-1 gene (FBN1) which results in a larger than normal protein that is more susceptible to proteolysis.
Immunolocalization confirmed increased expression of MCP-3 in the dermis of 4 of 5 Tsk1 skin samples and 14 of 28 lesional SSc skin samples, compared with that in matched healthy mice (n = 5) and human controls (n = 11).
A multilocus 2-cM haplotype was identified on human chromosome 15q homologous to the murine tsk1 region, which showed a significantly increased frequency in SSc cases compared with controls.
Real time quantitative polymerase chain reaction targeting the Y chromosome specific sequence DYS14 was employed to test DNA extracted from peripheral blood mononuclear cells of 26 women with systemic sclerosis and 23 healthy women who had never given birth to a son.