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PubMed2005

The differential expression of VEGF, VEGFR-2, and GLUT-1 proteins in disease subtypes of systemic sclerosis.

Our aim was to evaluate (a) whether there is differential expression of the endothelial regulator vascular endothelial growth factor (VEGF), its receptor (VEGFR-2), and the hypoxia-associated glucose transporter molecule, GLUT-1, in skin biopsies from different disease subtypes of systemic sclerosis (SSc) and (b) whether they associate with dermal calcinosis, a significant complication of SSc. Skin punch biopsies were taken from the forearms of 66 SSc patients including 18 with limited cutaneous disease without calcinosis (lcSSc), 23 with calcinosis (lcSSc/cal), and 25 with diffuse cutaneous disease (dcSSc) and from 12 healthy control subjects. The histological appearance of the skin was graded as G0 (normal), G1 (dermal edema), or G2 or G3 (increasing fibrotic changes). Immunohistochemistry was performed with antibodies to VEGF, VEGFR-2, and GLUT-1. Staining was assessed in the epidermis, microvessels, and fibroblasts. The Kruskal-Wallis 1-way analysis of variance was used to compare the data between disease groups. VEGF protein was located in the epidermis and in dermal endothelial cells, pericytes, fibroblasts, and inflammatory cells. In dcSSc only, there was a significant increase in VEGF staining intensity in the keratinocytes and pericytes and the lowest percentage of microvessels with VEGF-positive endothelial cells. GLUT-1 protein was located in the epidermis, erythrocytes, and perineurium. In both lcSSc/cal and dcSSC, but not lcSSc, there were significant increases in GLUT-1 staining intensity of keratinocytes. We propose that in patients with dcSSc, there is a net increase in unbound VEGF in skin that may account for the raised levels of VEGF in serum reported by others. Increased GLUT-1 expression in lcSSc/cal and dcSSc indicates that hypoxia is an associated factor.

Adult↗
PubMed2004

Increased prevalence of ocular glaucomatous abnormalities in systemic sclerosis.

BACKGROUND: Cardiovascular diseases, vasospasm, and dysimmunity have been implicated in normal tension glaucoma (NTG). OBJECTIVE: To investigate the prevalence of ocular abnormalities suggestive of glaucoma damage in systemic sclerosis (SSc). METHODS: 61 patients with SSc (mean (SD) age 56.2 (12) years, mean (SD) disease duration 9.9 (9) years; 41 with limited cutaneous disease) and 37 control subjects with osteoarthritis (mean (SD) age 55.9 (12) years) were studied. They were systematically referred to an ophthalmologist. The evaluation was based on aplanation tonometry, ophthalmoscopy with retinal photography (evaluation of cup/disc ratio (c/d)), and automated static perimetry (determination of mean defects (MD)). Statistical analyses were performed with the chi(2), Mann-Whitney, and Spearman tests. RESULTS: The mean visual acuity and intraocular pressure were similar in both groups. An excavation with a c/d >0.3 was found in 27 eyes from patients with SSc and 5 eyes from controls (p = 0.009); a c/d >0.7 was found in 4 eyes from patients with SSc and none in the controls (NS). Visual field defects (MD <-2 dB) were found in 55 eyes from patients with SSc and in 18 eyes from controls (p<0.0001). A concomitant c/d >0.3 and MD <-2 dB was found in 21 eyes from 12 patients with SSc but in none of the control eyes (p<0.0001). CONCLUSION: Ocular abnormalities suggesting glaucomatous neuropathy without ocular hypertension were dramatically more prevalent in patients with SSc. These abnormalities seem to be mild but justify long term follow up. They are consistent with the vascular pathogenic hypothesis for NTG.

Adult↗
PubMed2006

[Bosentan for treatment of active digital ulcers in patients with systemic sclerosis].

OBJECTIVES: To describe the effect of bosentan and its dual inhibition of endothelin-1 ETA and ETB receptors on digital ulcers in patients with systemic sclerosis (SSc). METHODS: Patients receiving bosentan for SSc-related digital ulcers were identified in eight centers, and their characteristics and follow-up were recorded. RESULTS: Nine (six with diffuse and three with limited cutaneous forms of SSc) patients (median age: 54 years) had received bosentan for digital ulcers. Complete healing occurred in seven (median time to improvement: 4 weeks). Another experienced a significant decrease in the number of ulcers (from 22 to 5) in 8 weeks, while one had no improvement. After a median follow-up of 24.3 months, only one recurrence was observed. Raynaud phenomenon improved in all but one patient. DISCUSSION: These data suggest that some patients may benefit from bosentan to treat digital ulcers. The short time to healing in these patients with rather chronic ulcers argues strongly in favor of its use. These results also strengthen the evidence that endothelin-1 plays an important role in the vascular manifestations of SSc. CONCLUSION: Bosentan can be effective in the treatment of digital ulcers in some SSc patients with SSc, probably especially those involving substantial ischemia. Bosentan is not a first-line drug in this indication yet and must be carefully used by specialists in SSc. Forthcoming results from the international RAPIDS-2 study should clarify the indications for bosentan in the treatment of SSc-related digital ulcers.

Adult↗
PubMed2005

Clinical significance of serum levels of matrix metalloproteinase-13 in patients with systemic sclerosis.

OBJECTIVES: To investigate the clinical significance of serum matrix metalloproteinase-13 (MMP-13) levels in patients with systemic sclerosis (SSc). METHODS: Serum MMP-13 levels were determined by using a peptide substrate cleavage assay in 20 patients with diffuse cutaneous SSc (dcSSc), 20 with limited cutaneous SSc (lcSSc) and 10 normal controls. RESULTS: The serum MMP-13 levels in patients with dcSSc or lcSSc were significantly lower than those in normal controls (53.4 +/- 14.1 vs 73.2 +/- 11.5 ng/ml, P < 0.0005; 59.4 +/- 14.8 vs 73.2 +/- 11.5 ng/ml, P < 0.005, respectively), but there was no significant difference in the serum MMP-13 levels between patients with dcSSc and those with lcSSc. Disease duration prior to the diagnosis was significantly shorter in SSc patients with decreased serum MMP-13 levels than in those with normal levels (3.0 +/- 2.2 vs 8.6 +/- 7.6 yr, P < 0.0005). In addition, serum MMP-13 levels were moderately correlated with the duration of the disease (r = 0.451, P < 0.05). Though there was no significant difference in the frequencies of pulmonary fibrosis or reduced %DLco (diffusing capacity of lung for carbon monoxide), the frequency of reduced %VC (vital capacity) was significantly greater in patients with decreased serum MMP-13 levels than in those with normal levels (73 vs 24%, P < 0.05). CONCLUSIONS: Matrix metalloproteinase-13 may be involved in the fibrotic process of SSc, especially in the initiation of fibrosis. The serum MMP-13 levels may serve as a useful marker for the severity of pulmonary fibrosis in patients with SSc.

Adult↗
PubMed2006

Disease subsets, antinuclear antibody profile, and clinical features in 127 French and 247 US adult patients with systemic sclerosis.

OBJECTIVE: To investigate the specificities of antinuclear antibodies (ANA) associated with systemic sclerosis (SSc) disease classification and internal organ involvement among patients with SSc of different origins (European and American). METHODS: Serum samples from 374 adult patients diagnosed with SSc were studied: 127 French patients (Paris) were compared with 247 US patients (Pittsburgh). Patients were classified into diffuse cutaneous (dc) and limited cutaneous (lc) SSc subsets. Antibodies associated with SSc were determined by protein and/or RNA immunoprecipitation, indirect immunofluorescence, and immunodiffusion. RESULTS: SSc classification differed significantly in the 2 cohorts: lcSSc and overlap patients with lcSSc combined made up 76% of the French series versus 52% of the US group (p < 0.0001). The frequency of anti-RNA polymerase III antibody was significantly increased in US patients compared with French patients (p < 0.0001). The frequency of anti-topoisomerase I (topo I) antibody was significantly increased among French patients (p < 0.0048). Anti-topo I-positive French SSc patients were less likely to have dcSSc (38% vs 65%) and more likely to have milder disease than US anti-topo I-positive patients. The French dcSSc patients had lower proportions of joint/tendon manifestations and renal crisis (7% vs 17%), but more often had radiographic evidence of pulmonary fibrosis (57% vs 30%). French lcSSc patients had a lower frequency of pulmonary arterial hypertension than US lcSSc patients (9% vs 31%; p = 0.002). CONCLUSION: There are disease classification and SSc-related serum autoantibody differences between French and American patients with SSc. These differences help to explain variations in clinical features reported from different geographic regions.

Adult↗
PubMed2004

Association between systemic sclerosis and breast cancer: eight new cases and review of the literature.

Several studies have demonstrated an increased frequency of cancer in patients with systemic sclerosis (SSc), specially lung and breast cancers. The pathogenesis of the association between SSc and cancer is not fully established. The aim of this study was to describe new cases of the association between SSc and breast cancer and to perform a review of the literature. We retrospectively studied the medical files of eight patients followed in our institution for SSc and breast cancer. We analyzed them with data available in the literature for a total of 46 patients. Cutaneous extension of SSc was clearly mentioned in 17 cases: the SSc was limited in 10 cases and diffuse in 7 cases The median age at the diagnosis of cancer was 54 years (range: 40-71). The median duration between SSc onset and breast cancer diagnosis was 11.5 months (range: 0-288). The duration between SSc onset and breast cancer diagnosis was < or = 12 months in 27 of 44 patients (61.4%), and in 11 (25%) of them the diagnosis of both diseases was made simultaneously. It was clearly mentioned for 35 patients whether the diagnosis of breast cancer was made before or after the onset of SSc. The diagnosis of breast cancer was made before SSc onset in 17 of 35 patients (48.6%) and after SSc onset in 18 of 35 patients (51.4%). For 33 patients, the follow-up was available: 18 (54.5%) died, 11 (33.3%) of them within the 1st year after the diagnosis of the cancer. For none of the patients did the anticancer treatment improve the SSc. The close temporal relationship between SSc onset and breast cancer diagnosis is highly suggestive of a pathophysiological link. SSc is probably not a paraneoplastic disease since the anticancer treatment has no influence on the evolution of SSc. However, it can be suggested that SSc could be a disease facilitating breast cancer and/or metastases development.

Adult↗
PubMed2006

Variations of neuronal nitric oxide synthase in systemic sclerosis skin.

OBJECTIVE: In systemic sclerosis (SSc), derangement of the peripheral nervous system is linked to vascular tone dysfunction. Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS, NOS-I) might play a dynamic role in the control of vascular tone. This study was performed to verify, by immunohistochemical and biochemical analyses, the presence and expression of nNOS and protein gene product 9.5 (PGP 9.5) in SSc skin, in different subsets and various phases of the disease. METHODS: Biopsy samples of clinically involved skin from 32 SSc patients (12 with limited cutaneous SSc [lcSSc] and 20 with the diffuse form [dcSSc]) and skin samples from 6 healthy controls were either immunostained with anti-PGP 9.5 and anti-nNOS antibodies or analyzed by semiquantitative reverse transcription-polymerase chain reaction and Western blotting. RESULTS: Immunohistochemical and biochemical data showed a decrease in PGP 9.5 and nNOS innervation and in their messenger RNA (mRNA) levels in lcSSc and dcSSc skin. In the edematous phase of SSc, a light alteration in cutaneous innervation was initiated and slowly progressed into the sclerotic phase, becoming most evident in the atrophic phase. Levels of nNOS mRNA were significantly lower between the edematous phase and the sclerotic phase in both dcSSc and lcSSc skin, which was attributable to the earlier occurrence of more severe pathologic alterations. CONCLUSION: Total cutaneous innervation and nNOS innervation slowly disappear in the skin of SSc patients. Expression of nNOS depends on the severity of tissue damage in SSc, and increased synthesis of NO also contributes to this process. It remains to be determined whether the changes in cutaneous innervation are due to the disease itself or whether these changes contribute to the pathogenesis and evolution of SSc.

Female↗
PubMed1995

Elevated levels of eosinophil major basic protein in the sera of patients with systemic sclerosis.

OBJECTIVE: To examine eosinophil activation, as reflected by evidence of eosinophil degranulation in the blood and affected tissues, in patients with diffuse and limited cutaneous forms of systemic sclerosis (SSc). METHODS: Levels of the eosinophil-derived major basic protein (MBP), a marker of eosinophil degranulation, were determined in sera from 46 SSc patients, from patients with rheumatoid arthritis and giant cell arteritis, and from healthy volunteers, and in bronchoalveolar lavage fluid from 4 SSc patients. Extracellular tissue deposition of MBP was evaluated in biopsy specimens from affected skin or lung of 11 SSc patients. RESULTS: Patients with diffuse cutaneous SSc (dcSSc) had elevated serum MBP levels compared with normal individuals (mean +/- SD 762 +/- 271 ng/ml versus 534 +/- 144 ng/ml; P = 0.0004). MBP levels were positively correlated with the extent of cutaneous involvement, and negatively correlated with pulmonary function and duration of disease (r = -0.20). By immunohistochemical analysis, modest extracellular MBP deposition could be demonstrated in involved skin in 7 of 10 biopsy specimens, and MBP staining was prominent in affected lung tissues in 2 patients. CONCLUSION: Eosinophil degranulation appears to be increased in some patients with dcSSc, as indicated by elevated serum levels of MBP and extracellular accumulation of MBP in the lung. Eosinophil granule proteins may contribute to the development of cutaneous and pulmonary fibrosis in SSc.

Adult↗
PubMed2001

Anti-agalactosyl IgG antibodies in sera from patients with systemic sclerosis.

OBJECTIVE: To determine the prevalence and clinical correlations of anti-agalactosyl IgG antibodies (anti-AG IgG) in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc; n = 49), diffuse cutaneous SSc (dSSc; n = 21), rheumatoid arthritis (RA; n = 10), systemic lupus erythematosus (SLE; n = 20), and healthy individuals (n = 20) were examined by lectin-enzyme immunoassay using human agalactosyl IgG as antigen. RESULTS: Anti-AG IgG were detected in 52 (74%) of 70 patients with SSc, which was much higher than the frequency of rheumatoid factor positivity in SSc (16%). Levels of anti-agalactosyl IgG antibodies were significantly higher than in healthy controls or patients with SLE, but lower than patients with RA. Levels of anti-AG IgG in patients with dSSc were significantly higher than in lSSc. SSc patients with anti-topoisomerase I antibodies had significantly higher levels of anti-AG IgG than SSc patients with anticentromere antibodies. Concerning clinical correlation, patients with pulmonary fibrosis showed elevated levels of anti-AG IgG compared to those without pulmonary fibrosis. Patients with decreased %VC or %DLCO showed increased levels of anti-AG IgG. Elevated levels of anti-AG IgG were associated with the presence of contracture of phalanges or cutaneous calcinosis, but not the presence of arthritis/arthralgia. CONCLUSION: The results suggest that anti-agalactosyl IgG antibody is frequently detected in SSc and is a serological indicator for more severe SSc.

Adolescent↗
PubMed2006

[Clinical associations of C-reactive protein in systemic sclerosis].

AIM: To evaluate incidence of C-reactive protein (CRP) rise and CRP associations with clinical manifestations in systemic sclerosis (SS). MATERIAL AND METHODS: CRP concentrations in blood serum were estimated with solid phase enzyme immunoassay in 21 SS patients (8 patients with diffuse SS--dSS and 13 patients with limited SS--lSS). Two patients with ISS had documented rheumatoid arthritis (RA)--SS/RA. Forty two healthy donors with normal levels of CRP served control. RESULTS: CRP was elevated in 10 (48%) of 21 SS patients. Mean CRP content was 9.87 +/- 7.73 mg/l (about 3 times higher than in the control group, p < 0.0001) in 20 eligible patients. A mean CRP level did not differ between ISS and dSS patients. RA patients had higher levels of CRP (p = 0.001). CRP was elevated in 4 of 5 (80%) patients with digital ulcers and only in 5 (27%) of 15 patients without ulcers, but the difference was insignificant as well as those in mean CRP in these subgroups. Content of von Willebrand factor antigen (Ag:vW) was high in 7 (33%) patients (mean 1.70 +/- 0.84 IU/ml) this being significantly higher than in the control group (p < 0.0001). CPR concentration closely correlated with that of Ag:vW (r = 0.52; p = 0.017). Close association was found between CRP level and ESR (r = 0.75; p < 0.001) and titer of antinuclear factor (r = 0.52; p = 0.035). CONCLUSION: A moderate rise of CRP level in about 50% cases of SS is associated with arthritis and cutaneous ulcers. A positive correlation between CRP content and Ag:vW in blood suggests that CPB concentrations may reflect severity of vascular damage in SS.

Adult↗
PubMed1994

Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide.

OBJECTIVE: Pulmonary fibrosis is a common feature of systemic sclerosis (SSc) and a major cause of morbidity and mortality. Since alveolitis may be an essential step in the development of pulmonary fibrosis, we investigated the use of immunosuppressive drug therapy to improve pulmonary function in patients with SSc. METHODS: Eighteen patients with progressive pulmonary dysfunction, diminished vital capacity (VC), and/or decreased static lung compliance (Cst) were treated with cyclophosphamide and corticosteroids for 1 year. Eight patients had diffuse cutaneous SSc and 10 had limited cutaneous SSc. The median disease duration was 2.5 years (range 0.5-17 years). RESULTS: VC increased in 14 of 18 patients and the median VC rose from 74% to 80% of predicted. Cst improved in 8 of 12 patients and the median Cst increased from 59% to 66% of predicted. Pulmonary nonfibrotic opacities disappeared in 9 of 12 patients. The erythrocyte sedimentation rate (ESR) and serum concentrations of orosomucoid, C-reactive protein, and aminopropeptide type III collagen all improved. The patients were divided into 2 groups based on the presence or absence of elevations in acute-phase protein levels and ESR before therapy. Among the 12 patients with biochemical signs of inflammation, VC increased in 11, and Cst improved or was unchanged in 7 of the 8 who were tested. The median VC in this subgroup increased from 73% to 80% of predicted and the median Cst increased from 57% to 60% of predicted. In the group of 18 patients overall, the skin score decreased, while esophageal and renal function remained stable. CONCLUSION: Cyclophosphamide may have a beneficial effect on pulmonary fibrosis in patients with SSc and elevated levels of acute-phase proteins. Controlled trials of cyclophosphamide in pulmonary SSc should be performed and should focus on such patients.

Adult↗
PubMedDate not supplied

Combined treatment with calcipotriol ointment and low-dose ultraviolet A1 phototherapy in childhood morphea.

Various therapies for morphea have been used with limited success, including ones with potentially hazardous side effects. When morphea occurs in childhood it may lead to progressive and long-lasting induration of the skin and subcutaneous tissue, growth retardation, and muscle atrophy. We report an open prospective study in which the efficacy of a combined treatment with calcipotriol ointment and low-dose ultraviolet A1 (UVA1) phototherapy in childhood morphea was investigated. Nineteen children (mean age 8.5 years, range 3-13 years) with morphea were exposed to UVA1 (340-400 nm) phototherapy at a dose of 20 J/cm(2) four times a week for 10 weeks. Forty phototherapy sessions resulted in a cumulative dose of 800 J/cm(2) UVA1. In addition, calcipotriol ointment (0.005%) was applied twice a day. After 10 weeks, palpation and inspection showed a remarkable softening and repigmentation of formerly affected skin resulting in a highly significant (p < 0.001) decrease of the mean clinical score from 7.3 +/- 0.9 at the beginning to 2.4 +/- 0.9 (relative reduction 67.1%) at the end of combined therapy. Our results indicate that a combined therapy with calcipotriol ointment and low-dose UVA1 phototherapy is highly effective in childhood morphea. Further controlled studies are necessary to investigate whether this combined therapy is superior to UVA1 phototherapy alone.

Adolescent↗
PubMed2005

[Efficacy of anti-thymocyte globulin and cyclosporin A combined therapy in aplastic anemia complicated with limited cutaneous systemic sclerosis].

We reported here on a case of limited cutaneous systemic sclerosis (lcSSc) with aplastic anemia treated by anti-thymocyte globulin and cyclosporin A. The use of this therapy resulted not only in marrow recovery but also in resolution of the skin sclerosis. A 68 year-old woman was diagnosed as lcSSc accompanied by Hashimoto's thyroiditis and primary biliary cirrhosis. Treatment by D-penicillamine was started. After 11 months, She complained of nasal bleeding and subcutaneous bleeding. Her laboratory data revealed pancytopenia. White blood cell count, hemoglobin concentration and platelet count were decreased at 2300/microl, 8.2 g/dl, and 3000/microl respectively. Bone marrow was severely hypoplastic, suggesting aplastic anemia. The etiology of hypopastic marrow was considered to be D-penicillamine which had been frequently reported to cause hematopoietic cell suppression. We immediately started methylprednisolone pulse therapy combined with G-CSF and cyclosporin A, which showed little effectiveness. Next we tried the anti-thymocyte globulin therapy combined with G-CSF and cyclosporin A. Her blood cell counts gradually improved. After 4 months, she did not need the blood transfusion anymore. Furthermore, the sclerosis of her skin began to improve gradually, and the titer of anti-centromere antibody also decreased. Thus, anti-thymocyte globulin and cyclosporin A combined therapy can be considered among the therapies of systemic sclerosis.

Aged↗
PubMed1997

Relationship between cutaneous and pulmonary involvement in systemic sclerosis.

OBJECTIVE: Pulmonary disease may shorten survival in patients affected by systemic sclerosis (SSc). However, pulmonary involvement may commonly be silent, whereas skin fibrosis is usually the clinical feature drawing most attention. We investigated the relationship between cutaneous and pulmonary involvement during SSc. METHODS: We studied 52 patients (mean age 50.2 +/- 13.7 years) affected by SSc (mean duration of disease 13.8 +/- 9.5 years). Twenty-eight had the diffuse form of the disease (dSSc) and 24 the limited form (lSSc). All patients underwent pulmonary function studies, high resolution computed tomography (HRCT) of the lungs, and complete echocardiographic examination. Pulmonary artery systolic pressure was measured by Doppler echocardiography. Pulmonary interstitial fibrosis and skin fibrosis were evaluated using a point system. RESULTS: Mean percentages of predicted values of forced vital capacity and total lung capacity were significantly reduced in patients with dSSc compared to lSSc (80.0 +/- 18.9 vs 98.4 +/- 16.8%, p < 0.001; and 81.3 +/- 13.9 vs 92.1 +/- 14.2%, p < 0.01, respectively). The overall HRCT score was 6.1 +/- 4.9, with no significant differences between disease subgroups. However, a HRCT score of 10 or more was present in 10 patients with dSSc vs 2 patients with lSSc (p = 0.02). Pulmonary hypertension was present in 27 patients, 15 with lSSC and 12 with dSSc (p = NS). No significant correlation was observed between skin score and lung volumes, carbon monoxide diffusing capacity, HRCT score, or pulmonary artery systolic pressure for all patients and subgroups. CONCLUSION: Extent and severity of cutaneous and pulmonary involvement in SSc are not directly correlated. Nevertheless, different patterns of pulmonary involvement between SSc subgroups were observed. Restrictive lung disease was more frequent in patients with dSSc, while a trend to higher prevalence of pulmonary hypertension was observed in patients with lSSc.

Adult↗
PubMed2003

[Extracorporeal photopheresis in progressive systemic sclerosis: discrimination of responders and non-responders].

BACKGROUND: The benefit of extracorporeal photopheresis (ExP) in progressive systemic sclerosis (PSS) is controversial. There is limited experience with the long-term use of ExP in PSS. The purpose of the present study was to distinguish between responders and non-responders by using ExP in PSS and to evaluate activation markers for PSS. PATIENTS AND METHODS: 20 subjects with PSS were treated for 12 months with ExP (interval: 1x/month) as an immunomodulating monotherapy (11/20) or combination therapy (9/20). The course of PSS was assessed by both specially designed clinical score and serological parameters (CRP, ANA, beta-galactosidase, P-III-P, CD4/CD8-ratio, TNF-alpha, 11-2-R, 11-6). RESULTS: After 12 cycles of ExP, 30% of the subjects showed a partial remission and 25%, stable disease (55% responders) while 45% had a progression (non-responders). Although there was no correlation between the clinical course and the serological parameters, an increase of beta-galactosidase during therapy marked a progression of PSS in non-responders. Responders with a short PSS-course before ExP, moderate ANA titres, normal TNF-alpha levels and lack of Scl-70 had a good prognosis. CONCLUSIONS: About the half of the subjects with PSS profited by the long-term use of ExP. Thereby the mild immunomodulating effect of ExP seems to be insufficient to control markedly progressive courses of PSS.

Adult↗
PubMedDate not supplied

Association between the HLA-DRB1 gene and clinical features of systemic sclerosis in Korea.

OBJECTIVE: To determine whether HLA-DR alleles are associated with the development and clinical features of systemic sclerosis (SSc) in Koreans. METHODS: Seventy-nine patients (74 women and five men; 45 diffuse types and 34 limited types; mean age at diagnosis 43.9 years) fulfilling the American College of Rheumatology (ACR) classification criteria for SSc were enrolled. The controls were 144 healthy, disease-free Koreans. HLA-DRB1 genotypes were assessed by the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. RESULTS: The HLA-DRB1*15 allele was increased in anti-topoisomerase I autoantibody (anti-topo I)-positive SSc patients [p = 0.003, p corrected (p(corr)) = 0.039, odds ratio (OR) = 3.43, 95% confidence interval (CI) 1.45-8.13] compared with controls. The DRB1*11 allele was also observed more frequently in anti-topo I-positive SSc than in controls (13.3% vs. 4.2%) but not statistically significant (p = 0.053, p(corr) = 0.689). In patients with SSc, the DRB1*04 allele was associated with subcutaneous calcinosis (p = 0.048, OR = 4.56, 95% CI 1.07-19.37). Patients with overlap syndrome showed a negative association with the DRB1*04 allele (p = 0.036, OR = 0.26, 95% CI 0.08-0.91). CONCLUSION: The HLA-DRB1*15 allele was associated with the development of anti-topo I-positive SSc in Koreans. In addition, the DRB1*04 allele was associated with certain clinical features in SSc patients.

Female↗
PubMed1998

Antigen specificity of antihistone antibodies in systemic sclerosis.

OBJECTIVES: The aim of the study was to determine the prevalence and clinical significance of antibodies to individual histone components in systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc; n = 42) and diffuse cutaneous SSc (dSSc; n = 28) were examined for IgG and/or IgM antibodies to individual histone components and complexes by enzyme linked immunosorbent assay (ELISA). RESULTS: The level of IgG antibody to total histones was significantly higher in lSSc and dSSc than in normal controls. The level of IgM antibody to total histones was significantly higher in lSSc, but not in dSSc, than in normal controls. IgG antibody to total histones tended to be increased in dSSc when compared with that in lSSc. On the other hand, IgM antibody to total histones tended to be increased in lSSc when compared with that in dSSc. Although SSc showed various antihistone specificities, H2B, H2A-H2B, (H2A-H2B)-dsDNA were main antigens recognised by IgG antibodies in both lSSc and dSSc. Although IgM antibodies to H2B and H2A-H2B were also detected in both lSSc and dSSc, serum samples from lSSc patients exhibited highest IgM reactivity with H1. CONCLUSION: SSc may be included among conditions in which heterogeneous antihistone antibodies are produced. IgM antibodies to the most accessible histone H1 may be related to mild clinical features (lSSc) and IgG antibodies to the inner core molecules of native histone such as H2B or complexes including H2B may be associated with severe clinical features (dSSc) in Ssc.

Adult↗
PubMed2001

Pulmonary function tests, high-resolution computerized tomography, alpha1-antitrypsin measurement, and early detection of pulmonary involvement in patients with systemic sclerosis.

OBJECTIVE: Pulmonary disease represents a major complication of systemic sclerosis (SSc). However, pulmonary involvement is commonly silent. In this study, we investigated the relationship between serum alpha1-antitrypsin and other means of assessing pulmonary involvement. METHODS: Twenty-two patients affected by SSc were studied (mean age 37.6+/-14.3 years, mean duration of disease 9.9+/-11.9 years). Fourteen had the diffuse form of disease (dSSc) and eight had the limited form (lSSc). All patients underwent pulmonary function tests, high-resolution computed tomography (HRCT) of the lungs, echocardiography, and serum assessment of alpha1-antitrypsin. RESULTS: Mean percentage of predicted values of forced vital capacity was lower in patients with dSSc than with lSSc (72.3+/-17.8 vs 74.5+/-8, P=NS). Mean percentage of predicted values of forced expiratory volume in 1-s forced vital capacity (FEV1/FVC) was lower in patients with lSSc (79.8+/-7.5 for lSSc vs 84.4+/-7.8 for dSSc, P= NS). The overall HRCT score was 5.6+/-5.9 with no significant difference between disease subgroups. Pulmonary hypertension was detected in two cases, both with dSSc. Alpha1-antitrypsin was significantly higher in patients than in controls (P < 0.01), with no significant difference between disease subgroups, and correlated significantly with ground glass opacities in H RCT (P < 0.05) and the detection of diffusion defects (r= -0.61, P<0.01). No significant correlation was observed between skin score or degree of dyspnea with HRCT score, lung volume, or carbon monoxide diffusing capacity. CONCLUSION: Restrictive lung disease was more pronounced in patients with dSSc. Alpha1-antitrypsin levels correlated significantly with ground glass opacities, an early finding of pulmonary involvement in SSc. Extent and severity of skin involvement and degree of dyspnea were not related to pulmonary involvement.

Adolescent↗