Relationship between clinical phenotype and autoantibodies in systemic sclerosis / 西安交通大学学报(医学版)

【Objective】 To detect autoantibodies in Chinese systemic sclerosis (SSc) patients and analyze the relationship between clinical phenotype and autoantibodies in SSc. 【Methods】 We sequentially included 93 SSc patients. Their general information and clinical data were gathered. The differences in clinical characteristics among autoantibody negative and positive groups were analyzed statistically. 【Results】 Anti-nuclear antibodies were detected in 82 (88.2%) SSc patients. The positive rate of autoantibodies was detected in 26 cases (28.0%) of anti-Scl-70 antibody, 24 cases (25.8%) of anti-SSA/Ro-52 antibody, 19 cases (20.4%) of anti-U1-snRNP antibody, and 16 cases (17.2%) in anti-CENP-B antibody, respectively. The patients with positive anti-SSA/Ro-52 antibody had a significantly higher morbidity rate of pulmonary arterial hypertension (P=0.016). Patients with anti-Scl-70 antibody showed a higher incidence rate of digital tip ulcers or gangrene (P=0.004) and cardiac damage (P=0.014). The patients with anti-U1-snRNP antibody had a higher prevalence of pulmonary arterial hypertension (P=0.047) and Raynaud’s phenomenon (P=0.019), and showed an increased trend in the occurrence of interstitial lung disease (P=0.058). Those with anti-CENP-B antibody had a lower IgG level (P=0.049) and higher ALP (P=0.010) and γ-GT (P=0.003). The incidence of autoimmune liver disease was increased in anti-CENP-B positive patients (P=0.001). 【Conclusion】 Different autoantibodies in SSc are associated with clinical phenotype, and may contribute to the diagnosis, evaluation, and prognostic judgment of the disease.

Clinical significance of PM-Scl antibody detection in systemic scleroderma / 国际检验医学杂志

Objective To analyze and discuss the expression of serum polymyositis‐scleroderma(PM‐Scl) antibody and its clinical significance in patients with systemic scleroderma(SSc) .Methods 315 hospitalized patients diagnosed with scleroderma by typical clinical manifestations or skin pathology from 2009 to 2012 were enrolled in the study .All patients were grouped into PM‐Scl antibody positive(PM‐Scl + ) group(90 cases) ,Scl‐70 antibody positive(Scl‐70+ ) group(70 cases) ,anti‐centromere antibody positive( ACA+ ) group(75 cases) and antibody negative group(80 cases) according to autoantibody spectrum .The severity of skin and visceral damage among all the groups were analyzed and compared .Results Patients in PM‐Scl+ group were characterized with different clinical manifestations .Compared with the other 3 groups ,the incidence of myositis in PM‐Scl+ group was significantly higher( all P< 0 .05) ;patients in Scl‐70+ group had higher incidence of visceral organ damage than PM‐Scl+ group(all P < 0 .05) .The incidence of skin lesions ,Raynaud′s phenomenon and capillary expansion in ACA+ group were higher than that of PM‐Scl+ ,while the incidence of interstitial lung disease ,heart disease and kidney disease were lower(all P< 0 .05) .Conclusion It is helpful for clinicists′ further understanding of common autoantibodies in Ssc patients and making correct assessment of the disease through analyzing the expression of PM‐Scl antibody .

The detection of scleroderma-related autoantibodies and its clinical significance in 135 Chinese patients with systemic sclerosis / 中华微生物学和免疫学杂志

Objective To detect the expression of scleroderma-related autoantibodies, such as anti-Scl-70, anli-centromere antibody ( ACA)and anti-RNA polymerase Ⅲ ( ARA) , and their relationship with clinical features in Chinese systemic sclerosis (SSc) patients. Methods One hundred and thirty-five Chinese SSc patients from the clinical database of the Scleroderma Trials and Research Group proposed by European League Against Rheumatism's Scheroderma Trial and Research Group( EUSTAR) were consecutively enrolled. The expression of ARA, anti-Scl-70 and ACA were detected through linear immunoblotting, double immunodiffusion and indirect irnmunofluorescence, respectively. The relevance between the existing of autoantibodies and clinical manifestations was analyzed statistically. Results Among the 135 Chinese SSc patients, the prevalence of anti-Scl-70, ACA, ARA were 49. 6% , 13.3 % and 8.9% respectively. Patients with anti-Scl-70 antibody had significantly shorter disease course [(71 ±59) month vs (90 ± 103) month, P = 0.041] , higher proportion of interstitial lung disease ( P = 0. 031) but lower of pulmonary arterial hypertension (P =0.042). Modified Rodnan's skin score (P=0.008) and prevalence of facial and cervical cutaneous sclerosis (P = 0. 002) , distal (to elbow/knee ) cutaneous sclerosis ( P = 0. 004 ) and digital pitting scarring/disappear of digital pad were all significantly higher in anti-Scl-70 positive group. Patients with AC A had longer disease course ( P = 0. 036) , lower IgM level ( P = 0. 045) and were less prevalent of interstitial lung disease ( P =0. 045). Patients with ARA had higher serum creatinine and urea nitrogen level ( P ＜ 0.001) although otherwise features had unremarkable differences. Conclusion Scleroderma-related autoantibodies have relevance with different clinical manifestation and detection of these autoantibodies may be helpful to the diagnosis of SSc, organ involvement evaluation and predicting outcomes. The clinical relevances of autoantibodies in Chinese SSc patients may differ from other areas or races.

Compromiso pulmonar en esclerosis sistémica / Lung involvement in systemic sclerosis

El objetivo del estudio fue determinar las características clínicas de los pacientes con esclerodermia y compromiso pulmonar y evaluar si existen factores clínicos predictores de mayor riesgo de enfermedad intersticial. Se estudiaron en forma retrospectiva 40 pacientes con esclerodermia. Fueron divididos en 2 grupos: capacidad de difusión del monóxido de carbono (DLCO) normal (n = 22) y DLCO disminuida (n = 18, 45%). Los pacientes con DLCO disminuida no fueron diferentes en edad (51.1 más o menos 13.5 vs. 53.5 más o menos 9.3 años, p = 0.5182), sexo (varones 13.6%, p = 0.6088 ), presencia de Raynaud (86.6% vs. 85%, p = 0.6272), síndrome de ojo seco (6.2% vs. 10.5%, p = 1.0000) prevalencia de enfermedad difusa (94.1% vs. 83.3%, p = 0.6026) o de dilatación esofágica. El tiempo de evolución de la enfermedad no fue diferente. La sensibilidad de la disnea para detectar una DLCO alterada fue 46.6% con una especificidad del 90% y la de la caída de la saturación de O2 (SaO2) del 71.4% y 80% respectivamente. Los pacientes con DLCO baja tuvieron mayor prevalencia de anticuerpos anti-Scl 70 positivos (5/9 vs. 0/11, p = 0.0081) y de incapacidad ventilatoria restrictiva aunque en 56.7% de los pacientes con DLCO disminuida la capacidad pulmonar total (CPT) era normal. La presencia de hipertensión pulmonar medida por ecocardiograma Doppler fue idéntica (11/13 vs. 10/11, p = 1.0000). Los pacientes con DLCO disminuida tuvieron una prevalencia muy superior de tomografía computada de tórax con evidencias de compromiso intersticial (82.3% vs. 5.8%, p menor o igual a 0.0001). En conclusión, nuestros datos sugieren que la disminución de la DLCO es un hallazgo, muy frecuentemente asociado a TAC de tórax con compromiso intersticial y que no hay variables clínicas que permitan predecir su anormalidad.

The objective of this study was to determine clinical predictors of interstitial lung disease in patients with systemic sclerosis (SSc) and pulmonary involvement as defined by presence of a decreased diffusing capacity for carbon monoxide (DLCO). Forty subjects with SSc were retrospectively evaluated. Patients were categorized according to their level of DLCO (less than or more than or equal to 80% of predicted). Sensitivity of dyspnea to detect a decreased DLCO was 46.6% and specificity 90%, whereas oxygen desaturation showed a sensitivity of 71.4% and a specificity of 80%. Patients with decreased DLCO (n = 18) were not different in age (51.1 more or less than 13.5 vs. 53.5 more or less than 9.3 y, p = 0.5182), sex (male 13.6%, p = 0.6088), prevalence of Raynaud (86.6% vs. 85%, p = 0.6272), sicca syndrome (6.2% vs. 10.5% p = 1.0000) diffuse cutaneous involvement (94.1% vs. 83.3%, p = 0.6026) or esophageal dilatation. The duration of symptoms since diagnosis was no different. Prevalence of pulmonary hypertension assessed by Doppler echocardiography or abnormal nailfold capillaroscopic findings were identical in both populations. Patients with low DLCO had a significatly higher prevalence of anti topoisomerase antibodies. (5/9 vs. 0/11, p = 0.0081) and restrictive lung disease. Patients with low DLCO showed a significantly higher prevalence of abnormal HRCT findings suggestive of ILD (82.3% vs. 5.8%, p less than or equal to 0.0001). We conclude that a low DLCO is a frequent finding in SSc patients, strongly associated with HRCT signs of ILD. We have not found clinical factors predictive for a low DLCO.

Association of HLA - DR Genes with Systemic Sclerosis in Koreans / 대한류마티스학회지

OBJECTIVE: This study was conducted to elucidate the associations of HLA with systemic sclerosis (SSc) in Koreans. METHODS: HLA associations with SSc according to SSc-specific autoantibody status and clinical subsets (diffuse and limited) were investigated. HLA-A, B, and C antigens were typed by the serological method using microlymphocytotoxicity test, and HLA-DR by DNA typing method using PCR-reverse hybridization and PCR-SSCP in 56 Korean patients with SSc and 226 healthy controls. For SSc patients, anti-Scl-70 and anicentromere antibodies were tested by double immunodiffusion and indirect immunofluorescence, respectively. RESULTS: The results of HLA class I antigen typing showed that the frequencies of HLA-A24, B52 and B62 were increased, whereas those of A33, B44 and B58 were decreased in SSc patients compared to healthy controls. The frequency of HLA-DR2 was significantly increased, whereas that of HLA-DR13 was decreased in patients with SSc compared to controls. Among HLA-DR2 alleles, both HLA-DRB1*1501 and *1502 were increased in SSc patients compared to controls. According to clinical status, HLA-DRB1*1501 was increased in limited SSc patients and that of DRB1*1502 was increased both in diffuse and limited SSc patients compared to controls. According to autoantibody status, HLA- DRB1 1502 was significantly increased in anti-Scl-70-positive SSc patients and that of DRB1 1501 was increased in anti-Scl-70-negative SSc patients compared to controls. The association of HLA-DR2 alleles with SSc according to clinical subsets and anti-Scl-70 antibody status revealed that the frequency of HLA- DRB1 *1501 was significantly increased in anti-Scl-70-negative limited SSc patients compared to controls. CONCLUSIONS: These results suggest that different HLA-DR2 alleles are associated with different types of SSc in Koreans. HLA-DRB1 1502 shows strong association with anti-Scl-70-positive SSc, and DRB1 1501 with anti-Scl-70-negative limited SSc. It is concluded that the pathogenesis of SSc in Koreans is in part, based on the same genetic background.