SAT0326 SYSTEMIC SCLEROSIS WITHOUT ANTINUCLEAR ANTIBODIES: A MULTI-CENTER STUDY OF EUSTAR COHORT IN CHINA

Background:The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation and malfunction in patients with systemic sclerosis (SSc)[1]. A variety of ANAs[2], including anti-centromere antibody, anti-topoisomerase I antibody, and anti-RNA polymerase III antibody, are associated with unique sets of disease manifestations and widely used in routine clinical practice for diagnosis, clinical subgrouping, risk stratification and prediction of future organ involvements and prognosis in SSc patients[3,4].Objectives:This study aimed to investigate the clinical features of SSc patients with negative ANAs in a European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) and Chinese Rheumatism Data Center (CRDC) multi-center cohort in China.Methods:Patients were prospectively recruited between April 2008 and June 2019 based on the EUSTAR database and CRDC multi-center cohort from 154 clinical centers nationwide, all of whom fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Antinuclear antibody testing result was intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those with negative ANAs. T-test and chi-square analysis were performed in the comparisons.Results:Antinuclear antibodies were detected in 2129 out of 2809 systemic sclerosis patients enrolled in the multi-center cohort and 4.2% of them were negative. There was significant difference between patients with negative and positive ANAs based on gender (29/60 vs 294/1746, p<0.001). The presence of Raynaud’s phenomenon is less common (71.8% vs 99.8%, p<0.001) in the ANA-negative patients. In addition, compared with ANA-positive patients, the incidence of certain critical organ involvements, including gastroesophageal reflux (5.6% vs 18.5%, p=0.002), interstitial lung disease (65.2% vs 77.9%, p=0.015) and pulmonary arterial hypertension (11.5% vs 29.0%, p=0.006) were significantly lower in ANA-negative patients than in the positive group. The proportion of IgG elevation, an indicator of disease activity and severity of inflammation, was significantly lower in the ANA-negative patients than that in the positive group (14.3% vs 41.2%, p<0.001), while no significant differences were found in other inflammatory indicators and skin scores.Conclusion:This study describes the clinical features of SSc patients with negative ANAs, which have been rarely mentioned or focused in existing studies. Antinuclear antibody is proved to be strongly associated with the clinical manifestations of systemic sclerosis patients and ANA-negative SSc patients tend to be in relatively milder conditions, including a less common involvement of critical organs and a more temperate inflammatory severity.References:[1]Seri, Jeong, Dahae, et al. Diagnostic value of screening enzyme immunoassays compared to indirect immunofluorescence for anti-nuclear antibodies in patients with systemic rheumatic diseases: A systematic review and meta-analysis. [J]. Seminars in arthritis and rheumatism, 2018.[2]Hesselstrand, R. The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis[J]. Rheumatology, 2003, 42(4):534-540.[3]Behmanesh F, Amin R, Khajedaluee M, et al. Autoantibody Profile in Systemic Sclerosis[J]. Acta Medica Iranica, 2010, 48(1):12-20.[4]Hachulla E, Dubucquoi S. Nuclear auto-antibodies: a useful tool for the diagnosis, the classification and the prognosis of systemic sclerosis. [J]. La Revue de Médecine Interne, 2004, 25(6):442-447.Disclosure of Interests:None declared

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Systemic Sclerosis Patients With Negative Antinuclear Antibodies Have Distinctive Clinical Manifestations: a Multicenter CRDC Cohort in China

10.21203/rs.3.rs-147806/v1 ◽

2021 ◽

Author(s):

Min Hui ◽

Jiaxin Zhou ◽

Liyun Zhang ◽

Xinwang Duan ◽

Mengtao Li ◽

...

Keyword(s):

Systemic Sclerosis ◽

Data Center ◽

Antinuclear Antibodies ◽

Laboratory Data ◽

Clinical Manifestations ◽

Organ Involvement ◽

Multicenter Cohort ◽

Significant Difference ◽

Critical Organ ◽

Pulmonary Arterial

Abstract Objective: The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc). A variety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice for diagnosis, clinical subgrouping, and prediction of future organ involvement and prognosis in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in a Chinese Rheumatism Data Center (CRDC) multicenter cohort in China.Methods: Based on the CRDC database, patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs.Results: Antinuclear antibodies were detected in 2129 of 2809 patients enrolled in the study; 4.2% patients were negative. There was a significant difference between patients negative and positive for ANAs based on sex (29/60 vs 294/1746, p＜0.001). The presence of Raynaud’s phenomenon was less common (71.8% vs 91.8%, p＜0.001) in the ANA-negative patients. In addition, the incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs 18.5%, p=0.002), interstitial lung disease (65.2% vs 77.9%, p=0.015) and pulmonary arterial hypertension (11.5% vs 29.0%, p=0.006), was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal ESR (32.4% vs 47.6%, p=0.013) and IgG elevation (14.3% vs 37.0%, p=0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients.Conclusion: Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease.

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Anti-RNA Polymerase III Antibody Prevalence and Associated Clinical Manifestations in a Large Series of French Patients with Systemic Sclerosis: A Cross-sectional Study

The Journal of Rheumatology ◽

10.3899/jrheum.090677 ◽

2009 ◽

Vol 37 (1) ◽

pp. 125-130 ◽

Cited By ~ 41

Author(s):

OLIVIER MEYER ◽

LUC DE CHAISEMARTIN ◽

PASCALE NICAISE-ROLAND ◽

JEAN CABANE ◽

FLORENCE TUBACH ◽

...

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Topoisomerase I ◽

Rna Polymerase Iii ◽

Laboratory Data ◽

Clinical Manifestations ◽

The United States ◽

Cutaneous Disease ◽

Polymerase Iii ◽

Renal Crisis

Objective.To determine the prevalence of anti-RNA polymerase III autoantibodies in French patients with systemic sclerosis (SSc) and to identify the associated clinical manifestations.Methods.Consecutive patients with SSc seen in 3 tertiary centers in Paris were included. Sera samples were collected together with the relevant clinical and immunological data. Anti-RNA polymerase III antibodies were detected by ELISA at a central laboratory. Data on other antibodies were abstracted from the medical records.Results.We included 319 patients: 84% women, 36% with a diffuse cutaneous subtype, 44% with pulmonary fibrosis, 5% with pulmonary hypertension, 4% with renal crisis, among whom 29 (9.4%) had anti-RNA polymerase III antibodies. These antibodies were more prevalent in patients with diffuse than with limited cutaneous disease (14.3% vs 6.0%; OR 2.6, 95% CI 1.2–5.48, p = 0.016). Renal crisis was more prevalent in patients with than in those without anti-RNA polymerase III antibodies (14% vs 3%; OR 5.0, 95% CI 1.4–17.3, p = 0.012). Renal crisis occurred in 2.2% of patients with anti-topoisomerase I and 3.9% of patients with anticentromere antibodies. Of the patients with anti-RNA polymerase III antibodies, 24 (83%) had no other systemic sclerosis-specific autoantibodies.Conclusion.The prevalence of anti-RNA polymerase III antibodies in French patients appeared to be lower than in the United States and similar to that in continental Europe. These antibodies were consistently associated with diffuse cutaneous disease and were the most common immunological marker for renal crisis. Anti-RNA polymerase III determination can help to risk-stratify SSc patients at high risk for this severe manifestation.

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Late onset systemic sclerosis with seronegativity: a rare presentation of an uncommon disease

Reumatismo ◽

10.4081/reumatismo.2019.1170 ◽

2019 ◽

Vol 71 (3) ◽

pp. 166-170

Author(s):

D. Saxena ◽

D. Jain ◽

M. Yadav ◽

K. Giri ◽

T. Yadav ◽

...

Keyword(s):

Systemic Sclerosis ◽

Topoisomerase I ◽

Antinuclear Antibodies ◽

Late Onset ◽

Rna Polymerase Iii ◽

Connective Tissue Disorder ◽

Internal Organs ◽

Rare Presentation ◽

Multisystem Involvement ◽

Uncommon Disease

Systemic sclerosis (SSc) is an uncommon connective tissue disorder characterized by multisystem involvement with fibrosis of skin and internal organs. Antibody formation is one of the hallmarks of SSc. Antinuclear antibodies (ANA) are positive in 97% of patients with SSc. We report a rare case where the patient was negative for ANA, Anti-topoisomerase I, Anti-centromere and Anti-RNA polymerase III antibodies.

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AB0557 CO-EXISTENCE OF SYSTEMIC SCLEROSIS HALLMARK AUTOANTIBODIES ASSOCIATES WITH DISTINCT CLINICAL PHENOTYPE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3500 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1575.2-1575

Author(s):

C. Campochiaro ◽

K. Clark ◽

L. Host ◽

A. Sari ◽

S. Nihtyanova ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Clinical Features ◽

Topoisomerase I ◽

Clinical Phenotype ◽

Rna Polymerase Iii ◽

Scleroderma Renal Crisis ◽

Fisher Exact Test ◽

Pulmonary Arterial

Background:Systemic sclerosis (SSc) is typically manifests with distinct SSc-specific antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA), anti-RNA polymerase III (ARA), anti-U3RNP (u3RNP), anti-U1RNP (U1RNP), anti-PmScl (PmScl), anti-Ku (Ku) and anti-Th/T0 (Th/T0), each being characterised by different clinical features and prognosis. The presence of >1 SSc-Abs is rare with minimum data about these patients’ clinical phenotype.Objectives:To describe and compare the clinical features of SSc patients with >1 SSc-AbMethods:The autoantibody profiles of 2799 SSc patients from February 2001 to June 2017 were retrospectively reviewed. Patients with >1 SSc-Abs were identified. Clinical features were collected and compared to historical cohorts of SSc patients with single SSc-Ab positivity. Patients were excluded if treated prior to their immunology test with rituximab, iv immunoglobulins or stem cell transplantation. Statistical analysis was performed using Fisher exact test.Results:72 patients (2.6%) with >1 SSc-Ab were identified. Full clinical data were available for 63 patients. 60 patients (2.1%) had double Ab positivity and 3 patients had triple Ab positivity (0.1%). 13 Ab combinations were present. U1RNP and ATA was the most frequent combination (35%), patients were significantly younger (51.38 years) than both U1RNP (58.64 years, p=0.050) and ATA (62.03 years, p=0.002) patients and more commonly of diffuse subset (dcSSc) (p=0.001 and p=0.041 respectively). Compared to ATA patients overlap features were more frequent (43% vs 15%, p=0.004) including inflammatory arthritis (p=0.025) and myositis (p=0.013) (Table 1). U1RNP and ACA had a significantly higher prevalence of pulmonary arterial hypertension compared to U1RNP (p=0.039) and ACA (p=0.022) patients, and compared to ACA patients they were younger (57.88 vs 68.75, p=0.015) with a higher incidence of myositis (p=0.001). U1RNP and ARA patients were more frequently dcSSc subtype compared to U1RNP patients (75% vs 21%, p=0.040). U1RNP and PmScl patients had a higher prevalence of myositis compared to U1RNP patients (p=0.006). ATA and ACA patients behaved similarly to ATA patients with a significantly higher prevalence of lung fibrosis (p=0.006) and myositis (p=0.041) compared to ACA. ACA and PmScl (7%) had higher prevalence of myositis compared to ACA patients (p=0.04).Table 1. Frequency of clinical features in some of the double antibody group combinations, compared to our cohort of patients with only one of the SSc specific antibody. Significant p values (<0.05) highlighted in bold. ILD (interstitial lung disease), PAH (pulmonary arterial hypertension), SRC (scleroderma renal crisis).Conclusion:Coexistence of hallmark autoantibodies is exceedingly rare in SSc patients. When combined, both SSc-Abs have the potential to synergistically interact and modify the clinical phenotype.Disclosure of Interests:Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Kristina Clark: None declared, Lauren Host: None declared, Alper Sari: None declared, Svetlana Nihtyanova: None declared, Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Voon Ong: None declared

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AB0566 NAILFOLD EXTENT OF REDUCED CAPILLARY DENSITY IS ASSOCIATED WITH DIGITAL ULCERS AND WITH AN INCREASED RISK OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4173 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1580.2-1580

Author(s):

R. De Angelis ◽

F. Salaffi

Keyword(s):

Systemic Sclerosis ◽

Laboratory Data ◽

Quantitative Measure ◽

Capillary Density ◽

Optical Probe ◽

Typical Feature ◽

Slight Reduction ◽

Digital Ulcers ◽

Increased Risk ◽

Significant Difference

Background:A growing evidence supports the role of microvasculopathy as a primary pathogenic event in systemic sclerosis (SSc). The most commonly used imaging technique to identify microangiopathy in SSc is high magnification videocapillaroscopy (NVC), and reduced capillary density and/or capillary loss, which is a typical feature of “scleroderma microangiopathy”, easily identified by NVC, has been associated with digital ulcers (DUs). Different approaches have been proposed to measure capillary density or capillary loss. Some of these were qualitative methods, others semi-quantitative, others only concerned a limited nailfold area, without ever evaluating the overall density, which is more suitable for quantitative estimate.Objectives:To assess the association between the extent of different values of nailfold capillary density and the presence of DUs and to identify the risk of developing DUs, based on quantitative parameters.Methods:The study involved 54 SSc selected patients (47 women and 7 men, mean age 59.5 years, 50 with limited and 4 with diffuse). The study population came from an ongoing database, that includes clinical and laboratory data of patients with definite SSc. A videocapillaroscope (VideoCap® 3.0, DS Medica, Milan, Italy) with a 200x optical probe was used. During examination, eight fingers (fingers 2–5 of each hand), 4 fields per finger, according to the standard literature were assessed. For each patient, a total of 32 images were collected, then classified as having either “normal”, “non-specific” or the “scleroderma pattern” (SP). Capillary density was defined as the number of capillaries/mm in the distal row, regardless of its shape and morphology. Avascular areas were defined by the absence of loops within a width/area extending over more than 500 microns. For each patient, the SP images were further graded with no/slight reduction of the capillary density (7-9 loops/mm) (NOR), with a well-defined reduction of capillary density (6-4 loops/mm) (RED) and with loss of capillaries (<4) plus avascular areas (AA). Then, the overall percentages were calculated (the number with SP, the number with NOR, with RED and with AA, respect to 32), thus obtaining the quantitative measures. All data were analysed using the MedCalc® version 18.6; 64-bit (MedCalc Software, Mariakerke, Belgium).Results:A total of 1728 images were analyzed. Patients with DUs were 16/54 (29.6%). All patients had a SP, but only five patients showed a SP along the entire nailfold. A comparison between patients with or without DUs showed a significant difference both for the overall extent of AA (p=0.032), and particularly for the overall extent of RED (p<0.001). No significant difference was found regarding the overall extent of the SP (p=0.085). Factor significantly associated with DUs in multivariate analysis was the overall extent of RED (p=0.0286). The ROC curve was very effective at discriminating the capillary feature able to distinguish patients with DUs from patients without DUs. The discriminatory power of the overall extent of RED was very good, with an AUC of 0.948 (95 % CI 0.852 ± 0.990). Then, we calculated the cut-off values of the overall extent of RED for presence/absence of DUs with the highest combination of sensitivity and specificity. The resulting cut-off value (Yourden index of 0.825) was >68.7 (sensitivity 92.31 %; specificity 90.24 %) with a LR+ of 9.46.Conclusion:Our data strongly support that the capillary density between 4 and 6 loops/mm is the best capillaroscopic quantitative measure associated with DUs and able to discriminate the probability of having DUs. If all SSc-specific antibodies and/or other laboratory/clinical parameters are not yet available, the overall capillary density can allow physicians to assess SSc patients easily, regarding DUs and risk for developing DUs.Disclosure of Interests:None declared

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Gastric Antral Vascular Ectasia and Its Clinical Correlates in Patients with Early Diffuse Systemic Sclerosis in the SCOT Trial

The Journal of Rheumatology ◽

10.3899/jrheum.121087 ◽

2013 ◽

Vol 40 (4) ◽

pp. 455-460 ◽

Cited By ~ 45

Author(s):

Emily W. Hung ◽

Maureen D. Mayes ◽

Roozbeh Sharif ◽

Shervin Assassi ◽

Victor I. Machicao ◽

...

Keyword(s):

Systemic Sclerosis ◽

Topoisomerase I ◽

Rna Polymerase Iii ◽

Negative Association ◽

Upper Gastrointestinal Endoscopy ◽

Gastric Antral Vascular Ectasia ◽

Clinical Correlates ◽

Vascular Ectasia ◽

Diffuse Systemic Sclerosis ◽

Vascular Ectasias

Objective.To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; “watermelon stomach”) in early diffuse systemic sclerosis (SSc).Methods.Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests.Results.Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Scl70) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003).Conclusion.Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Scl70 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc.

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The −670G>A polymorphism in the FAS gene promoter region influences the susceptibility to systemic sclerosis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.088989 ◽

2008 ◽

Vol 68 (4) ◽

pp. 584-590 ◽

Cited By ~ 24

Author(s):

V Liakouli ◽

M Manetti ◽

A Pacini ◽

B Tolusso ◽

C Fatini ◽

...

Keyword(s):

Systemic Sclerosis ◽

Topoisomerase I ◽

Gene Promoter ◽

Serum Levels ◽

Scleroderma Renal Crisis ◽

Genotype Distribution ◽

Healthy Individuals ◽

Soluble Fas ◽

Significant Difference ◽

Pulmonary Arterial

Objective:To evaluate the role of the single-nucleotide polymorphism (SNP) at position −670 in the FAS gene promoter (FAS−670G>A) in influencing the susceptibility, clinical features and severity of systemic sclerosis (SSc).Methods:350 white Italian SSc patients (259 with limited cutaneous SSc (lcSSc) and 91 with diffuse cutaneous SSc (dcSSc)) and 232 healthy individuals were studied. Patients were assessed for the presence of autoantibodies (anticentromere, anti-topoisomerase I (anti-Scl-70) antibodies), interstitial lung disease (ILD), pulmonary arterial hypertension and scleroderma renal crisis. FAS−670G>A SNP was genotyped by PCR restriction fragment length polymorphism assay. Serum levels of soluble FAS (sFAS) were analysed by ELISA.Results:A significant difference in FAS−670 genotype distribution was observed between SSc patients and healthy individuals (p = 0.001). The frequency of the FAS−670A allele was significantly greater in SSc than in controls (p = 0.001). No significant difference in genotype distribution and allele frequencies was observed between lcSSc and dcSSc, although a greater frequency of the FAS−670A allele was found in dcSSc. The FAS−670AA genotype significantly influenced the predisposition to SSc (OR 1.97, 95% CI 1.35 to 2.88, p = 0.001) and to both lcSSc (OR 1.84, 95% CI 1.23 to 2.75, p = 0.003) and dcSSc (OR 2.37, 95% CI 1.41 to 3.99, p = 0.001). FAS−670A allele frequency was greater, although not significantly, in anti-Scl-70 antibody-positive dcSSc and ILD dcSSc. sFAS was significantly higher in patients and controls carrying the FAS−670AA genotype compared with those carrying the FAS−670GG genotype (p = 0.003 in SSc, p = 0.004 in controls).Conclusion:The FAS−670A allele is significantly associated with susceptibility to SSc, suggesting a role for a genetic control of apoptosis in the pathogenesis of the disease.

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Association between gene expression profiling of skin lesion and autoantibody in patients with systemic sclerosis

10.1101/2020.04.12.20063131 ◽

2020 ◽

Author(s):

Jun Inamo

Keyword(s):

Gene Expression ◽

Systemic Sclerosis ◽

Skin Lesion ◽

Topoisomerase I ◽

Cellular Response ◽

Rna Polymerase Iii ◽

Functional Enrichment ◽

Keratinocyte Differentiation ◽

Study Cohort ◽

Specific Autoantibody

AbstractObjectiveThe aim of this study was to investigate relevance between type of autoantibody and gene expression profile in skin lesion of systemic sclerosis (SSc), and identify specifically dysregulated pathways.MethodsSixty-one patients with SSc from the Genetics versus Environment in Scleroderma Outcome Study cohort and thirty-six healthy controls (HC) are included. Differentially expressed genes (DEGs) were extracted and functional enrichment and pathways analysis were conducted.ResultsCompared with HC, lists consisting of 2, 71, 10, 144 and 78 DEGs were created for patients without specific autoantibody, anti-centromere (ACA), anti-U1 RNP (RNP), anti-RNA polymerase III (RNAP) and anti-topoisomerase I (ATA) antibody, respectively. While part of enriched pathways overlapped, distinct pathways were identified except those without specific autoantibody: keratinocyte differentiation in ACA, NF-kB signaling and cellular response to transforming growth factor beta stimulus in RNAP, interferon alpha/beta signaling of RNP and cellular response to stress in ATA.ConclusionPathogenic pathways were identified according to type of autoantibodies by leveraging gene expression data of patients and controls from multi-center cohort. The current study will promote to explore new therapeutic target for SSc.Key messageDistinct pathways are associated with type of autoantibody in skin lesion of systemic sclerosis.

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Progression of Nailfold Microvascular Damage and Antinuclear Antibody Pattern in Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.121089 ◽

2013 ◽

Vol 40 (5) ◽

pp. 634-639 ◽

Cited By ~ 20

Author(s):

Alberto Sulli ◽

Barbara Ruaro ◽

Vanessa Smith ◽

Carmen Pizzorni ◽

Giuseppe Zampogna ◽

...

Keyword(s):

Systemic Sclerosis ◽

Median Time ◽

Antinuclear Antibody ◽

Antinuclear Antibodies ◽

Rapid Progression ◽

Slight Reduction ◽

Nailfold Videocapillaroscopy ◽

Microvascular Damage ◽

Antibody Pattern ◽

Active Disease

Objective.This study evaluates possible correlations between the pattern of antinuclear antibodies (ANA) on indirect immunofluorescence (IIF) testing and nailfold microangiopathy stage (early, active, and late stage) in systemic sclerosis (SSc). Patients with SSc were followed prospectively to monitor progression of microvascular damage.Methods.The ANA pattern on IIF was searched in 42 patients with SSc showing an early pattern of nailfold microangiopathy at baseline, and was followed using nailfold videocapillaroscopy (NVC) for a median time of 91 months.Results.Among patients whose microangiopathy showed a rapid progression from early to late pattern on NVC, the IIF pattern was fine-speckled + nucleolar (Scl-70+) in 44%, centromeric in 33%, nucleolar in 11%, and homogeneous in 11% of patients with SSc. Antitopoisomerase I antibodies were significantly more frequent (57%) in patients with late pattern of microangiopathy on NVC. The median time of progression from early to active disease was significantly lower in patients with both fine-speckled + nucleolar and nucleolar ANA positivity. The severity of microangiopathy was higher in patients with the nucleolar pattern on IIF. Patients already showing a slight reduction of capillary number at baseline were likely to have either the nucleolar or the fine-speckled + nucleolar pattern on IIF. Of note, 37% of patients still showing the early microangiopathy pattern on NVC at the end of the followup were ANA-negative.Conclusion.ANA-negative patients with SSc display a slower progression of nailfold microangiopathy characterized by the early pattern on NVC. Progression to the late NVC pattern (more advanced stage of microvascular damage) seems to be associated with a different autoantibody pattern on IIF (fine-speckled + nucleolar pattern being the most prevalent).

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