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1.
Clin Rheumatol ; 37(4): 999-1009, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29214548

RESUMO

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.


Assuntos
Artralgia/etiologia , Hipertensão Pulmonar/etiologia , Doenças Pulmonares Intersticiais/etiologia , Doença de Raynaud/etiologia , Escleroderma Sistêmico/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Avaliação de Sintomas
2.
Tissue Antigens ; 80(3): 254-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22742541

RESUMO

Systemic sclerosis (SSc) is a complex autoimmune disease which genetic component has not been yet completely understood. IL6 encodes a cytokine with a crucial role in the development of autoimmunity and fibrosis and its actions mainly are controlled by IL-6 receptor (IL-6R). We aimed to investigate whether the functional genetic variants rs8192284 and rs2228044 previously associated with several autoimmune diseases, located within the IL-6 receptor (IL-6R) subunits IL6R and IL6ST genes, respectively, are involved in the susceptibility to SSc and/or its major clinical subphenotypes. A Spanish cohort including 1013 SSc patients and 1375 controls was genotyped using the TaqMan® allelic discrimination technology. SSc patients were subdivided according to the major clinical forms, autoantibody status and presence of fibrotic lung affection. Our data showed no influence of the selected variants in global SSc susceptibility (rs8192284: P=0.67, odds ratios (OR)=0.98; rs2228044: P=0.99, OR=1.00). Similarly, the clinical/autoantibody subphenotype analyses did not yielded significant results. Our data suggest that the analyzed polymorphisms may not play a significant role in the SSc susceptibility.


Assuntos
Receptor gp130 de Citocina/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptores de Interleucina-6/genética , Escleroderma Sistêmico , Estudos de Casos e Controles , Frequência do Gene/genética , Humanos , Escleroderma Sistêmico/genética
3.
Genes Immun ; 13(6): 458-60, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22551723

RESUMO

There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of ≤ 1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN ≥ 2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.


Assuntos
Deleção de Genes , Receptores de IgG/genética , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/imunologia , Autoanticorpos/sangue , Sequência de Bases , Estudos de Casos e Controles , Centrômero/imunologia , Variações do Número de Cópias de DNA , Sondas de DNA/genética , DNA Topoisomerases Tipo I/imunologia , Europa (Continente) , Grupo com Ancestrais do Continente Europeu/genética , Proteínas Ligadas por GPI/genética , Dosagem de Genes , Estudos de Associação Genética , Humanos , Fatores de Risco , Esclerodermia Difusa/genética , Esclerodermia Difusa/imunologia , Esclerodermia Limitada/genética , Esclerodermia Limitada/imunologia
4.
Genes Immun ; 13(2): 191-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22012429

RESUMO

Regulatory T cells (T(regs)) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor α (IL2RA) is an important T(reg) marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P(FDR)=2.07 × 10(-4), odds ratio=1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc.


Assuntos
Doenças Autoimunes/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Escleroderma Sistêmico/genética , Adulto , Doenças Autoimunes/imunologia , Loci Gênicos , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/imunologia
5.
BMJ ; 343: d6783, 2011 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-22108262

RESUMO

OBJECTIVE: To investigate the effect of an additional review based on reporting guidelines such as STROBE and CONSORT on quality of manuscripts. DESIGN: Masked randomised trial. Population Original research manuscripts submitted to the Medicina Clínica journal from May 2008 to April 2009 and considered suitable for publication. CONTROL GROUP: conventional peer reviews alone. Intervention group: conventional review plus an additional review looking for missing items from reporting guidelines. Outcomes Manuscript quality, assessed with a 5 point Likert scale (primary: overall quality; secondary: average quality of specific items in paper). Main analysis compared groups as allocated, after adjustment for baseline factors (analysis of covariance); sensitivity analysis compared groups as reviewed. Adherence to reviewer suggestions assessed with Likert scale. RESULTS: Of 126 consecutive papers receiving conventional review, 34 were not suitable for publication. The remaining 92 papers were allocated to receive conventional reviews alone (n=41) or additional reviews (n=51). Four papers assigned to the conventional review group deviated from protocol; they received an additional review based on reporting guidelines. We saw an improvement in manuscript quality in favour of the additional review group (comparison as allocated, 0.25, 95% confidence interval -0.05 to 0.54; as reviewed, 0.33, 0.03 to 0.63). More papers with additional reviews than with conventional reviews alone improved from baseline (22 (43%) v eight (20%), difference 23.6% (3.2% to 44.0%), number needed to treat 4.2 (from 2.3 to 31.2), relative risk 2.21 (1.10 to 4.44)). Authors in the additional review group adhered more to suggestions from conventional reviews than to those from additional reviews (average increase 0.43 Likert points (0.19 to 0.67)). CONCLUSIONS: Additional reviews based on reporting guidelines improve manuscript quality, although the observed effect was smaller than hypothesised and not definitively demonstrated. Authors adhere more to suggestions from conventional reviews than to those from additional reviews, showing difficulties in adhering to high methodological standards at the latest research phases. To boost paper quality and impact, authors should be aware of future requirements of reporting guidelines at the very beginning of their study. Trial registration and protocol Although registries do not include trials of peer review, the protocol design was submitted to sponsored research projects (Instituto de Salud Carlos III, PI081903).


Assuntos
Guias como Assunto , Revisão da Pesquisa por Pares , Publicações Periódicas como Assunto , Autoria/normas , Controle de Qualidade , Reprodutibilidade dos Testes
6.
Ann Rheum Dis ; 70(3): 454-62, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21131644

RESUMO

OBJECTIVE: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. METHODS: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. RESULTS: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected)=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected)=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected)=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). CONCLUSION: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.


Assuntos
Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Escleroderma Sistêmico/genética , Autoanticorpos/sangue , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Escleroderma Sistêmico/imunologia
7.
Hum Mol Genet ; 18(11): 2071-7, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19286670

RESUMO

The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.


Assuntos
Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT4/genética , Escleroderma Sistêmico/genética , Estudos de Casos e Controles , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/etnologia , Feminino , Genótipo , Humanos , Masculino , Fenótipo , Escleroderma Sistêmico/etnologia , Escleroderma Sistêmico/patologia
8.
Ann Rheum Dis ; 68(10): 1618-20, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19054816

RESUMO

OBJECTIVE: To conduct a replication study to investigate whether the -945 CTGF genetic variant is associated with systemic sclerosis (SSc) susceptibility or specific SSc phenotype. METHODS: The study population comprised 1180 patients with SSc and 1784 healthy controls from seven independent case-control sets of European ancestry (Spanish, French, Dutch, German, British, Swedish and North American). The -945 CTGF genetic variant was genotyped using a Taqman 5' allelic discrimination assay. RESULTS: An independent association study showed in all the case-control cohorts no association of the CTGF -945 polymorphism with SSc susceptibility. These findings were confirmed by a meta-analysis giving a pooled OR = 1.12 (95% CI 0.99 to 1.25), p = 0.06. Investigation of the possible contribution of the -945 CTGF genetic variant to SSc phenotype showed that stratification according to SSc subtypes (limited or diffuse), selective autoantibodies (anti-topoisomerase I or anticentromere) or pulmonary involvement reached no statistically significant skewing. CONCLUSION: The results do not confirm previous findings and suggest that the CTGF -945 promoter polymorphism does not play a major role in SSc susceptibility or clinical phenotype.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/genética , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Fenótipo , Regiões Promotoras Genéticas/genética
9.
Ann Rheum Dis ; 68(2): 253-6, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18713787

RESUMO

OBJECTIVES: Multiple studies indicate the role of the interleukin (IL)-17/IL-23 axis in autoimmune diseases, including systemic sclerosis (SSc). The aim of the current study was to investigate the possible implication of the IL23R gene in SSc susceptibility and/or clinical phenotype. METHODS: An initial case-control study in 143 Dutch patients with SSc and geographically matched healthy individuals (n = 246) was carried out and followed by a replication study in a cohort of 365 Spanish patients with SSc and 515 healthy individuals. Seven single nucleotide polymorphisms (SNPs) spanning the IL23R gene were selected and genotyped using a Taqman assay. RESULTS: Using a Dutch cohort of patients with SSc and controls we observed an association between two (rs11209032, rs1495965) of the seven tested SNPs and disease susceptibility (allelic p values: p = 0.02 and p = 0.01 respectively). However, a replication study in an independent Spanish cohort did not confirm these findings and reveal no association of any of the IL23R-tested SNP with disease susceptibility or clinical phenotype. Similarly, a meta-analysis considering both populations did not reveal any significant association. In addition, no association was observed between IL23R genetic variants and SSc clinical phenotypes. CONCLUSIONS: Our results suggest that the IL23R gene is not associated with SSc susceptibility or clinical phenotype.


Assuntos
Receptores de Interleucina/genética , Escleroderma Sistêmico/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único
10.
Rheumatology (Oxford) ; 42(1): 71-5, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12509616

RESUMO

OBJECTIVE: To determine survival and mortality in a cohort of Spanish patients with scleroderma (systemic sclerosis, SSc) and to analyse whether survival is influenced by demographic, clinical or immunological variables or the extent of skin involvement. METHODS: The study included 79 patients diagnosed with SSc and taking part in a study to determine the extent of sclerosis, visceral involvement and immunological alterations. We studied the number of observed and expected deaths (the expected number being based on age- and sex-specific rates in the background population) and derived standardized mortality ratios with their 95% confidence intervals (CI). Cumulative survival after onset of the first symptom was estimated according to the Kaplan-Meier method. The Cox method was used to identify the prognostic factors. RESULTS: The mortality rate was 0.0249 deaths per person-year. Survival at 15 yr was 0.62 (95% CI 0.410-0.778). The standardized mortality ratio was 429.4% (95% CI 222-750). On crude analysis, lung involvement [forced vital capacity (FVC) <70%, pulmonary hypertension], SSc renal crisis, an active capillaroscopic pattern, pericardial effusion and age over 60 yr at diagnosis were associated with shorter survival. On multivariate analysis, only age at diagnosis over 60 yr, FVC <70% and SSc renal crisis were independent prognostic factors. CONCLUSIONS: The mortality rate associated with SSc showed a four-fold increase compared with the background population. Lung involvement and sclerodermal renal crisis were found to be independently associated with reduced survival.


Assuntos
Escleroderma Sistêmico/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Intervalos de Confiança , Feminino , Seguimentos , Humanos , Rim/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fibrose Pulmonar/fisiopatologia , Estudos Retrospectivos , Risco , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Fatores Sexuais , Pele/patologia , Espanha , Taxa de Sobrevida
11.
Lupus ; 10(9): 628-31, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11678451

RESUMO

The objective of this study was to investigate the presence of nailfold capillary abnormalities and extrahepatic signs of connective tissue disease in patients with primary biliary cirrhosis (PBC), as compared to patients with other chronic liver diseases. We evaluated 22 patients with PBC and 15 patients with other chronic liver diseases as a control group. Nailfold capillaroscopy was performed by two observers blinded to clinical findings using a Wild M3 stereomicroscope with an Intralux 5000 Volpi cold light lamp. We detected nailfold capillary abnormalities in 20 out of 22 (91%) PBC patients. Twelve of these 20 patients (54%) showed capillary alterations characteristic of systemic sclerosis. In the control group only two out of 15 patients (13%) presented alterations and in both cases they were a non-specific type. The presence of nailfold capillary abnormalities was significantly greater in PBC patients than in the control group (P < 0.001). Eleven out of the 22 PBC patients (50%) had extrahepatic signs of connective tissue disease and most of them were related to systemic sclerosis; patients with other chronic liver diseases did not present rheumatic manifestations (P < 0.001). In PBC patients there was a significant association between systemic sclerosis capillary pattern and rheumatic manifestations (P < 0.03). The high prevalence of nailfold capillary abnormalities characteristic of systemic sclerosis in patients with PBC and the correlation with sclerodermal manifestations suggests that this capillaroscopic finding could be a useful indicator to investigate rheumatic manifestations in these patients.


Assuntos
Capilares/patologia , Doenças do Tecido Conjuntivo/patologia , Cirrose Hepática Biliar/patologia , Adulto , Idoso , Alcoolismo/patologia , Anticorpos Antinucleares/sangue , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/imunologia , Feminino , Hepatite C/patologia , Humanos , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/imunologia , Pessoa de Meia-Idade , Unhas/irrigação sanguínea , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia
12.
Scand J Gastroenterol ; 35(7): 705-10, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10972173

RESUMO

BACKGROUND: Manometric assessment of the gastro-esophageal junction (GEJ) is deceptive in that ignores key dynamic properties of the junction, such as resistance to flow and compliance. Our aim was to investigate the mechanical properties of the GEJ comprising intraluminal pressure (measured by manometry), resistance to flow and compliance (measured by resistometry). METHODS: We studied 8 healthy subjects, 11 patients with achalasia and 11 patients with scleroderma. We used a pneumatic resistometer, previously developed and validated in our laboratory. The resistometer consists of a flaccid polyurethane 5-cm cylinder connected to an electronically regulated nitrogen-injection system; the instrument records nitrogen flow through the cylinder while maintaining a constant pressure gradient between its proximal and distal ends. By placing the cylinder successively in the proximal stomach and along the GEJ we measured the GEJ-gastric resistance gradient (GEJ resistance minus gastric resistance) and were able to calculate the cumulative resistance (sum of resistance exerted at each pressure level), peak resistance (at any injection pressure), nil resistance point (injection pressure in mmHg at which GEJ resistance equals gastric resistance), and compliance slope (flow/pressure relationship). RESULTS: We found that GEJ resistance to flow (cumulative resistance, peak resistance, and nil resistance point) is significantly increased in achalasia and decreased in scleroderma (P < 0.05 versus health) while GEJ compliance is diminished in achalasia (P < 0.05 versus health) and normal in scleroderma. CONCLUSION: Achalasia is a disease characterized by increased GEJ resistance and rigidity. By contrast, although scleroderma is characterized by decreased GEJ resistance, GEJ compliance may be normal.


Assuntos
Acalasia Esofágica/fisiopatologia , Junção Esofagogástrica/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade
13.
Arthritis Rheum ; 43(4): 894-900, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10765936

RESUMO

OBJECTIVE: To elucidate whether oxidative injury occurs in systemic sclerosis (SSc) and whether it affects the erythrocyte membrane (EM) properties. METHODS: EM fluidity and lipid composition (cholesterol:phospholipid molar ratio [C:PL], fatty acid composition) were studied in 52 patients with SSc and in 53 subjects without SSc (32 with primary Raynaud's phenomenon [RP] and 21 healthy subjects [controls]). Fluidity was measured as the fluorescence anisotropy of the hydrophobic fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene). Lipid peroxidation products were determined as thiobarbituric acid-reactive substances (TBARS). RESULTS: EM fluidity was significantly lower in SSc patients than in primary RP patients and controls (P < 0.001). The EM C:PL molar ratio was significantly higher in SSc patients than in primary RP patients and controls (P < 0.05). Levels of EM polyunsaturated n6 fatty acids (PUFA n6) were significantly lower in SSc patients than in primary RP patients and controls (P < 0.001). TBARS were significantly increased in SSc patients compared with primary RP patients and controls (P < 0.001). Multiple regression analyses indicated that the reduced EM fluidity was partly due to its greater C:PL molar ratio, lower PUFA n6 content, and higher TBARS levels. EM fluidity was lower among patients with nailfold capillary loss (P < 0.001) and digital ischemic ulcers (P < 0.05). EM lipid peroxidation products were higher among patients with pulmonary involvement (bibasal pulmonary fibrosis [P < 0.05] and reduced levels of diffusing capacity for carbon monoxide [P < 0.001]) and among patients who were positive for anti-topoisomerase I antibodies (P < 0.05) or negative for anticentromere antibodies (P < 0.001). CONCLUSION: Our findings support the idea that oxidative injury occurs in SSc and that, through lipid peroxidation, it induces structural and functional changes of the EM that may contribute to the development of the microvascular abnormalities that are seen in the disease.


Assuntos
Membrana Eritrocítica/fisiologia , Peroxidação de Lipídeos , Lipídeos/sangue , Fluidez de Membrana , Escleroderma Sistêmico/sangue , Radicais Livres/farmacologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Escleroderma Sistêmico/fisiopatologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
14.
J Am Soc Nephrol ; 11(3): 434-43, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10703667

RESUMO

Laminin is the main noncollagenous constituent of the basement membrane, and its serum levels could reflect the metabolic changes that occur in the basement membrane. Severe endothelial injury with thickening of basement membrane is a characteristic feature of thrombotic microangiopathy (TMA). With this background, the aim of the study was to investigate in a prospective way (1) the relationship among serum Lam-P1, the extent of renal histopathologic lesions, and the biochemical parameters commonly used as markers of TMA activity, and (2) the usefulness of serum Lam-P1 concentrations as a renal outcome prognostic index. To this end, 18 consecutive patients with active biopsy-proven TMA with renal involvement were studied. One hundred and twenty-one healthy control subjects, 20 patients with systemic scleroderma without renal involvement, and 35 patients with systemic lupus erythematosus (20 without nephropathy and 15 with diffuse proliferative type 4 lupus nephritis) were used as control groups. In addition, to analyze the influence of either renal failure or hemodialysis therapy on serum Lam-P1 levels, 91 patients on regular hemodialysis therapy and 81 patients with predialysis chronic renal failure of different etiologies were included in the study. Serum Lam-P1 was determined by RIA at admission, on days 10 and 30 of follow-up in all patients, and after 6 and 12 mo of follow-up in all surviving patients. Serum lactate dehydrogenase, haptoglobin, platelet count, hemoglobin, and serum creatinine were determined as markers of endothelial dysfunction and hemolysis. At admission, serum levels of Lam-P1 were significantly higher in patients with TMA than in healthy control subjects (3.39 +/- 0.56 U/ml versus 1.40 +/- 0.18 U/ml; P < 0.0001). In addition, patients with TMA had significantly higher serum Lam-P1 levels than the other groups included in the study. At the first control, Lam-P1 correlated with lactate dehydrogenase (P = 0.006) and hemoglobin (P = 0.002). During follow-up, platelet count and hemolysis indicators normalized in all patients, while serum Lam-P1 decreased only in patients with renal function recovery. In multivariate analysis, serum creatinine and Lam-P1 at day 10 were the only independent predictors of renal outcome (r2 = 0.94; P < 0.0001) and also correlated with indices of histopathologic damage (P < 0.001). Serum Lam-P1 normalized in all patients with chronic renal failure in the samples obtained at 6 and 12 mo of regular hemodialysis after solving active TMA, thus suggesting that histopathologic lesions, but not renal function itself, would be mainly responsible for the high Lam-P1 serum concentrations detected in TMA. In conclusion, serum Lam-P1 concentrations are increased in patients with active TMA. Furthermore, patients with poor renal outcome show a prolonged increase of serum Lam-P1 that is related to the extent of renal histologic lesions. Unlike the biochemical markers of hemolysis commonly used to assess TMA activity, the sequential determination of serum Lam-P1 provides valuable information about long-term renal prognosis in patients with TMA.


Assuntos
Laminina/sangue , Fragmentos de Peptídeos/sangue , Trombose/sangue , Adulto , Biomarcadores/sangue , Humanos , Rim/patologia , Microcirculação , Pessoa de Meia-Idade , Concentração Osmolar , Prognóstico , Estudos Prospectivos , Trombose/patologia
15.
Med Clin (Barc) ; 113(20): 761-4, 1999 Dec 11.
Artigo em Espanhol | MEDLINE | ID: mdl-10680138

RESUMO

BACKGROUND: To describe the outcome of the pregnancy in patients with scleroderma. PATIENTS AND METHODS: Patients with scleroderma and control group were included in this retrospective study. Two groups were different in pregnant patients with scleroderma: pregnancy before scleroderma (A1) and pregnancy after scleroderma (A2). The presence of clinical problems during pregnancy and the outcome of scleroderma were collected in a questionnaire. Differences in the frequencies of complications were analyzed using the U Mann-Whitney, the chi-square or Fisher's exact test when necessary. RESULTS: The frequency of global fetal complications was increased in patients group, but there was no significantly increased frequency when variables were analyzed independently: number of births, miscarriages, fetal deaths, preterm births and low weight full term babies. There was no increased frequency of renal crisis, hypertension or eclampsia. Differences between diffuse and limited subsets were no observed. Improvement of scleroderma was seen in only 3 patients and worsening of skin thickening was experienced by 2 patients. CONCLUSIONS: The pregnant scleroderma patients are a group with high risk pregnancies and therefore well-supervised pregnancies are necessary.


Assuntos
Complicações na Gravidez/etiologia , Esclerodermia Localizada/complicações , Escleroderma Sistêmico/complicações , Adulto , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Humanos , Incidência , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Estudos Retrospectivos , Estatísticas não Paramétricas , Inquéritos e Questionários
17.
Ann Rheum Dis ; 56(12): 723-8, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9496151

RESUMO

OBJECTIVE: To identify survival prognostic factors and markers of morbidity among patients with systemic sclerosis (SSc). PATIENTS AND METHODS: The study included 72 patients diagnosed with SSc. According to the extent of skin involvement, three groups of patients were established: group 1, without sclerosis and with sclerosis of fingers and neck; group 2, with sclerosis of face and distal to elbows and knees; group 3, with generalised sclerosis including the trunk. All patients were included in a study protocol to determine visceral involvement. Cumulative survival after first symptom has been estimated according to the Kaplan-Meier method. The association between a hypothetical prognostic factor and cumulative survival after first symptom was assessed by log rank test. The association between a hypothetical risk factor and the prevalence of severe morbidity was assessed by the odds ratio. Multiple logistic regression models were used to identify the main predictors of severe morbidity. RESULTS: Survival was estimated to be 85% 10 years after first SSc symptom. Survival was higher among SSc patients with skin involvement distal to elbows and knees than among the rest of patients; a forced vital capacity (FVC) on spirometry lower than 70% of expected value was associated with a shorter survival, even after adjustment for diffuse SSc. Skin involvement proximal to elbows or knees was associated with a higher prevalence of severe morbidity (OR = 46.57; p < 0.001). According to a multiple logistic regression, severe morbidity was higher among patients with skin involvement proximal to knees or elbows (OR = 40.92; p < 0.001) or among patients with pulmonary hypertension detected by Doppler echocardiography (OR = 23.66 p < 0.001). CONCLUSIONS: In patients with SSc the extent of skin sclerosis was found to be a determining factor on the prognosis. According to skin sclerosis extent two main subsets of SSc patients with different survival incidence and degree of morbidity could be clearly established: limited SSc, formed by patients with no skin sclerosis or with sclerosis distal to elbows and knees and diffuse SSc, formed by patients with skin sclerosis distal and proximal to elbows and knees. Moreover, lung involvement (FVC < 70% on survival study and pulmonary hypertension on morbidity study) was an important and independent prognostic factor.


Assuntos
Escleroderma Sistêmico/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Morbidade , Prevalência , Prognóstico , Fatores de Risco , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/patologia , Espanha/epidemiologia , Taxa de Sobrevida , Capacidade Vital
18.
Br J Dermatol ; 135(4): 613-6, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8915158

RESUMO

We report a boy with overlap manifestations of systemic sclerosis and dermatomyositis (sclerodermatomyositis) whose disease showed a changing clinical pattern, and who had mechanic's hands, which are a cutaneous marker of myositis. Serological studies revealed antinuclear antibodies with a homogeneous nucleolar pattern. The anti-PM-Scl antibody was demonstrated by immunoblotting. HLA typing was positive for HLA-DR3/4. After a follow-up period of 11 years, no progression to severe systemic involvement was detected, and aggressive treatment was not administered. The recognition of subsets of patients with homogeneous clinical features and serological markers should permit the recognition of separate conditions among overlap syndromes. This would have prognostic and therapeutic implications.


Assuntos
Anticorpos Antinucleares/sangue , Dermatomiosite/imunologia , Dermatoses da Mão/imunologia , Escleroderma Sistêmico/imunologia , Criança , Dermatomiosite/patologia , Seguimentos , Dermatoses da Mão/patologia , Humanos , Masculino , Síndrome
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