Sclerosis Patients Research Articles

PP119-SUN: Outstanding abstract: Weight Gain in Amyotrophic Lateral Sclerosis (ALS) Patients Occurs Even with Stable Calorie Intake

PP119-SUN: Outstanding abstract: Weight Gain in Amyotrophic Lateral Sclerosis (ALS) Patients Occurs Even with Stable Calorie Intake

IL-23 Plasma level measurement in relapsing remitting multiple sclerosis (RRMS) patients compared to healthy subjects

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Interleukin-23 (IL-23), a member of the IL-12 cytokine family is a heterodimeric cytokine composed of the IL-12p40 subunit, and with a novel p19 subunit, its ability to enhance the expansion of T helper type 17 (Th17) cells indicates the responsibility for many of the inflammatory autoimmune responses.Objective: The objective of the project is to measure IL-23 level in plasma of multiple sclerosis (MS) patients in comparison with healthy control subjects.Methods: In a case-control study, plasma was collected from healthy subjects as control group (n = 40) and patients with relapsing remitting multiple sclerosis (RRMS) (n = 40). The plasma level of IL-23 was assessed by ELISA method. Statistical analysis was performed with SPSS (Ver. 16).Results: Plasma level of IL-23 in MS patients was significantly increased compared to control subjects (p Value < 0.001).Conclusions: Our findings revealed the increased IL-23 level in patients’ group. In conclusion, the inhibition of IL-23 might be a novel and promising therapeutic strategy, especially in the therapy of autoimmune inflammatory diseases. IL-23 plays a pivotal role in development of MS and might be a specific marker and therapeutic target for MS.

Molecular analysis of polimorphisms in HLA-CLASS II DRB1* and IL7Rα possibly associated with multiple sclerosis susceptibility in a population sample of Rio de Janeiro

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system (CNS) that affects mainly young adults. MS seems to be a polygenic and multifactorial disease, and genetic susceptibility has been associated mainly with the major histocompatibility complex (MHC), which in humans is the human leukocyte antigen (HLA). Among non-HLA genes is the alpha chain of interleukin 7 receptor gene (IL7Rα) at the 5p12-14 locus, also known as CD127. The aim of this study was to evaluate the correlations between polymorphism in the IL7Rα (rs6897932C) gene, HLA-class II DRB1* haplotypes and susceptibility to multiple sclerosis in patients with Recurrent Remitting form (RRMS). METHOD: In this study, peripheral blood samples were taken from 50 patients diagnosed using the diagnostic criteria for MS according to Polman (MacDonald) et al (2011). The patients were monitored at the Clinic of Neurology, Hospital Universitário Clementino Fraga Filho, along with 100 healthy control subjects matched for ancestry, sex and age. After DNA extraction by organic method, polymorphism +244 *C (rs6897932) was assessed by PCR followed by capillary electrophoresis on the ABI PRISM® 3500 Genetic Analyzer (Applied Biosystems, USA) platform. RESULTS: The results indicated a significant association between the CC haplotype and RRMS (p=0.02 , OR=2.14), as well as an association between the *C allele (CC and CT) and RRMS (p=0.042, OR=2.15). The same C allele was more frequent in the sample, both in patients (0.82), and in the control group (0.71). The sample, control group and patients included, was in Hardy- Weinberg equilibrium. The correlation between the presence of the CC genotype and HLA-DRB1* 15:01 was significant (OR=3.6, p=0.034). CONCLUSION: These results reinforce the polygenic/multifactorial characteristic or genetic heterogeneity of MS, indicating a relationship between putative polymorphism +244*C (CC genotype) in the IL7Rα gene and susceptibility to MS in the sample.

P914: Tracking disease progression in amyotrophic lateral sclerosis (ALS) patients using MUNE and macro-EMG

P914: Tracking disease progression in amyotrophic lateral sclerosis (ALS) patients using MUNE and macro-EMG

The verbal fluency index: Dutch normative data for cognitive testing in ALS

Objective: Executive dysfunction occurs in 30–50% of amyotrophic lateral sclerosis (ALS) patients and is most frequently assessed with the verbal fluency test. The verbal fluency index (VFI) has been developed to correct for slowness of speech in ALS, and reflects the average thinking time per word. However, its use as a marker of cognitive impairment is hindered by the absence of valid norm scores. Therefore, we provide normative data for the VFI. Methods: Dutch volunteers were demographically matched to the Dutch ALS population and completed the verbal fluency index (one-minute and three-minute spoken letter fluency). Multiple stepwise linear regression was performed to assess the influence of demographic variables, past medical history and medication use. Results: 273 volunteers participated in this study. Educational level was negatively correlated to one-minute and three-minute VFI performance (r = –0.3 and r = –0.4, p < 0.001, respectively). No correlations for age, gender, medication and past medical history were found. A formula for standardized z-scores, corrected for educational level, for the one-minute and three-minute VFI was calculated. Conclusions: We provide Dutch normative data for the spoken verbal fluency index, which can be used internationally, but validation in other languages is recommended. The findings illustrate the importance of valid disease-specific norm scores for time-dependent cognitive tests in ALS.

Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models.

Bioenergetic abnormalities and metabolic dysfunction occur in amyotrophic lateral sclerosis (ALS) patients and genetic mouse models. However, whether metabolic dysfunction occurs early in ALS pathophysiology linked to different ALS genes remains unclear. Here, we investigated AMP-activated protein kinase (AMPK) activation, which is a key enzyme induced by energy depletion and metabolic stress, in neuronal cells and mouse models expressing mutant superoxide dismutase 1 (SOD1) or TAR DNA binding protein 43 (TDP-43) linked to ALS. AMPK phosphorylation was sharply increased in spinal cords of transgenic SOD1G93A mice at disease onset and accumulated in cytoplasmic granules in motor neurons, but not in presymptomatic mice. AMPK phosphorylation also occurred in peripheral tissues, liver and kidney, in SOD1G93A mice at disease onset, demonstrating that AMPK activation occurs late and is not restricted to motor neurons. Conversely, AMPK activity was drastically diminished in spinal cords and brains of presymptomatic and symptomatic transgenic TDP-43A315T mice and motor neuronal cells expressing different TDP-43 mutants. We show that mutant TDP-43 induction of the AMPK phosphatase, protein phosphatase 2A (PP2A), is associated with AMPK inactivation in these ALS models. Furthermore, PP2A inhibition by okadaic acid reversed AMPK inactivation by mutant TDP-43 in neuronal cells. Our results suggest that mutant SOD1 and TDP-43 exert contrasting effects on AMPK activation which may reflect key differences in energy metabolism and neurodegeneration in spinal cords of SOD1G93A and TDP-43A315T mice. While AMPK activation in motor neurons correlates with progression in mutant SOD1-mediated disease, AMPK inactivation mediated by PP2A is associated with mutant TDP-43-linked ALS.

Clinical and paraclinical findings in natalizumab-associated infratentorial progressive multifocal leukoencephalopathy patients: Table 1

Natalizumab (NAT)-treated relapsing remitting multiple sclerosis (RRMS) patients have a marked progressive multifocal leukoencephalopathy (PML) risk, with an overall incidence of 3.4 per 1000 NAT treated patients (95%− CI 3.08 to 3.74).1 In HIV-positive PML patients a supratentorial manifestation occurred in 93.8%. An infratentorial PML manifestation is less frequent, occurring in 11–58.3% of the HIV-positive PML patients.2 ,3 Within the infratentorial brain structures, the pons is most commonly affected.2 Irie et al reported a infratentorial PML manifestation in one patient with renal failure. They found an overall survival of ≤4 months after onset of infratentorial PML symptoms.4 Up to now no clinical studies regarding NAT-PML with a predominant infratentorial manifestation have been published. Our study aimed to investigate differences in clinical data and disease course between NAT-PML patients with or without initial infratentorial involvement. NAT-PML patients treated in two German university hospitals (Bochum n=21, Hannover n=3,) until 1 November 2013 were included in this retrospective study (ethic committees: Bochum 4566–13, Hannover: 2100−2013). Treatment of NAT-PML was standardised including plasma exchange, mirtazapine and mefloquine treatment. Patients were followed for 14.6±12.4 months (mean±SD), basic characteristics and clinical data were collected by medical records. Extended Disability Status Scale (EDSS) and Karnofsky Index (KI) were performed at onset, after the immune reconstitution inflammatory syndrome (IRIS), and after 6 months post-NAT-PML diagnosis, 1,5-Tesla MRI scans were obtained. Compared with our preceding work,5 we focused on the speciality of infratentorial PML manifestations and included a larger patient population. Statistical analysis was performed using SPSS …

Interrelationship between brachial artery function and renal small artery sclerosis in chronic kidney disease

Chronic kidney disease (CKD), characterized by senile inflammation, is a risk factor for cardiovascular disease. Conduit artery function and small artery structure relate to cardiovascular disease. We examined the correlations, determinants and interrelationships of arterial indices in association with CKD in a cross-sectional study of 139 patients (60% male; mean age 44 years) with CKD (stages 3-5, 39%) who underwent a renal biopsy. Conduit artery function and small artery sclerosis were assessed by brachial artery flow-mediated dilatation (FMD) and semiquantitative evaluation of small artery intimal thickening (SA-IT), respectively. The estimated glomerular filtration rate correlated with FMD (r=0.31, P=0.0002) and inversely correlated with SA-IT (r=-0.54, P<0.0001). Multiple regression analysis showed that FMD was inversely correlated with SA-IT and vice versa. In addition, high-sensitivity C-reactive protein (hs-CRP) was significantly correlated with SA-IT, but not FMD. Multiple logistic analysis revealed that higher hs-CRP concomitant with decreased FMD was further associated with the risk of severe SA-IT compared with their individual effects. These findings suggest that both conduit artery and small artery disease develop with mutual interaction in parallel with decreased kidney function. Coexistence of inflammation and conduit artery dysfunction may be closely related to renal small artery sclerosis in patients with CKD.

Nonalcoholic Fatty Liver Disease Is Associated with Aortic Valve Sclerosis in Patients with Type 2 Diabetes Mellitus

BackgroundRecent epidemiological data suggest that non-alcoholic fatty liver disease (NAFLD) is closely associated with aortic valve sclerosis (AVS), an emerging risk factor for adverse cardiovascular outcomes, in nondiabetic and type 2 diabetic individuals. To date, nobody has investigated the association between NAFLD and AVS in people with type 2 diabetes, a group of individuals in which the prevalence of these two diseases is high.Methods and ResultsWe recruited 180 consecutive type 2 diabetic patients without ischemic heart disease, valvular heart disease, hepatic diseases or excessive alcohol consumption. NAFLD was diagnosed by liver ultrasonography whereas AVS was determined by conventional echocardiography in all participants. In the whole sample, 120 (66.7%) patients had NAFLD and 53 (29.4%) had AVS. No patients had aortic stenosis. NAFLD was strongly associated with an increased risk of prevalent AVS (odds ratio [OR] 2.79, 95% CI 1.3–6.1, p<0.01). Adjustments for age, sex, duration of diabetes, diabetes treatment, body mass index, smoking, alcohol consumption, hypertension, dyslipidemia, hemoglobin A1c and estimated glomerular filtration rate did not attenuate the strong association between NAFLD and risk of prevalent AVS (adjusted-OR 3.04, 95% CI 1.3–7.3, p = 0.01).ConclusionsOur results provide the first demonstration of a positive and independent association between NAFLD and AVS in patients with type 2 diabetes mellitus.

Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial

Patients who develop relapsing-remitting multiple sclerosis (MS) present with a first clinical demyelinating event. In this double-blind, multicentre, randomised, phase 3 study we investigated the effect of oral cladribine on conversion to clinically definite MS in patients with a first clinical demyelinating event, when given at the same doses shown to be effective in relapsing-remitting MS. Between Oct 21, 2008, and Oct 11, 2010, we recruited patients aged 18-55 years, inclusive, from 160 hospitals, private clinics, or treatment centres in 34 countries. Eligible patients had a first clinical demyelinating event within 75 days before screening, at least two clinically silent lesions of at least 3 mm on a T2-weighted brain MRI scan, and an Expanded Disability Status Scale score of 5.0 or lower. Patients with a first clinical demyelinating event ≤75 days before screening were randomly assigned (1:1:1) to receive cladribine tablets at cumulative doses of 5.25 mg/kg or 3.5 mg/kg or placebo. Randomisation was done with a central web-based randomisation system and was stratified by geographic region. Masking was maintained using a two-physician model. The primary endpoint of this 96-week study was time to conversion to clinically definite MS according to the Poser criteria. This study is registered with ClinicalTrials.gov, number NCT00725985. Of 903 participants assessed for eligibility, 616 patients received cladribine 5.25 mg/kg (n=204), cladribine 3.5 mg/kg (n=206), or placebo (n=206). At trial termination on Oct 25, 2011, cladribine was associated with a risk reduction versus placebo for time to conversion to clinically definite MS (hazard ratio [HR] for 5.25 mg/kg=0.38, 95% CI 0.25-0.58, p<0.0001; HR for 3.5 mg/kg=0.33, 0.21-0.51, p<0.0001). Adverse events were reported in 165 (81%) patients in the cladribine 5.25 mg/kg group, 168 (82%) patients in the cladribine 3.5 mg/kg group, and 162 (79%) patients in the placebo group. We noted no increase in risk of adverse events with active treatment versus placebo apart from lymphopenia, which was a severe event in 10 (5%) patients in the 5.25 mg/kg group and four (2%) patients in the 3.5 mg/kg group. Both doses of cladribine significantly delayed MS diagnosis compared with placebo. The safety profile of cladribine was similar to that noted in a trial in patients with relapsing-remitting MS. Further research could clarify the potential effects of oral cladribine treatment in the early stages of MS. Merck Serono SA Geneva, a subsidiary of Merck KGaA, Darmstadt, Germany.

The MoSt Project––More Steps in multiple sclerosis: a Delphi method consensus initiative for the evaluation of mobility management of MS patients in Italy

The aim of the study was to identify the main factors that impact mobility impairment in multiple sclerosis (MS) patients in Italy. Clinicians from a large number of Italian MS centers took part in a Delphi process aimed at obtaining consensus statements among the participants. Large consensus was obtained for statements grouped under the following main MS themes: identification of the most useful scales to evaluate mobility, integration of objective evaluation with patient perceptions, impact of walking impairment on daily life, management of the disabled patient using a rehabilitative and pharmacological approach. The consensus statements developed by a large number of experts may be used as a practical reference tool to help physicians treat MS patients with motor impairment.

Brain atrophy as a non-response predictor to interferon-beta in relapsing–remitting multiple sclerosis

Background:Several predictors for treatment failure to interferon-beta (IFN-beta) have been proposed; however, brain atrophy has not been well studied.Methods:In this prospective and longitudinal study, all consecutive relapsing–remitting multiple sclerosis (RRMS) patients treated with sc IFN-beta-1a were included. Confirmed disability progression or a new relapse between weeks 48 and 144 after beginning with IFN-beta was considered as treatment non-response. EDSS progression, relapses, number of active lesions at 1 year (new or enlarging T2-weighted plus gadolinium-enhancing lesions, categorized in > 2 or ≤ 2), and brain parenchymal fraction (%BVC) volume change within the initial year of treatment were used as predictive factors. Cox regression model was adjusted for age, gender, and disease duration.Results:Seventy-one patients were included (71·8% female) with a follow-up of 144 weeks. Thirty-four (48%) fulfilled criteria of non-response to IFN-beta treatment. The model showed: (1) relapses+disability progression: HR = 4·6, 95% IC: 3·1–6·7 (P < 0·001); (2) relapses+BVC decrease: HR = 4·1, 95% IC: 3·2–7·3 (P = 0·001); (3) relapses+disability progression+new active lesions: HR = 10·1, 95% IC: 7·1–15·2 (P < 0·001); and (4) relapses+disability progression+new active lesions+BVC decrease: HR = 14·4, 95% IC: 11·4–21·2 (P < 0·001).Conclusions:Adding BVC measures to previously described predictive failure factors may increase sensitivity to early identify non-responder patients to IFN-beta-1a in the second and third years of therapy.

Intensity Based Methods for Brain MRI Longitudinal Registration. A Study on Multiple Sclerosis Patients

Registration is a key step in many automatic brain Magnetic Resonance Imaging (MRI) applications. In this work we focus on longitudinal registration of brain MRI for Multiple Sclerosis (MS) patients. First of all, we analyze the effect that MS lesions have on registration by synthetically eliminating some of the lesions. Our results show how a widely used method for longitudinal registration such as rigid registration is practically unconcerned by the presence of MS lesions while several non-rigid registration methods produce outputs that are significantly different. We then focus on assessing which is the best registration method for longitudinal MRI images of MS patients. In order to analyze the results obtained for all studied criteria, we use both descriptive statistics and statistical inference: one way ANOVA, pairwise t-tests and permutation tests.

Spinal cord atrophy correlates with disease duration and severity in amyotrophic lateral sclerosis

Our objective was to investigate spinal cord (SC) atrophy in amyotrophic lateral sclerosis (ALS) patients, and to determine whether it correlates with clinical parameters.Forty-three patients with ALS (25 males) and 43 age- and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images covering the whole brain and the cervical SC to estimate cervical SC area and eccentricity at C2/C3 level using validated software (SpineSeg). Disease severity was quantified with the ALSFRS-R and ALS Severity scores. SC areas of patients and controls were compared with a Mann-Whitney test. We used linear regression to investigate association between SC area and clinical parameters. Results showed that mean age of patients and disease duration were 53.1 ± 12.2 years and 34.0 ± 29.8 months, respectively. The two groups were significantly different regarding SC areas (67.8 ± 6.8 mm² vs. 59.5 ± 8.4 mm², p < 0.001). Eccentricity values were similar in both groups (p = 0.394). SC areas correlated with disease duration (r = − 0.585, p < 0.001), ALSFRS-R score (r = 0.309, p = 0.044) and ALS Severity scale (r = 0.347, p = 0.022). In conclusion, patients with ALS have SC atrophy, but no flattening. In addition, SC areas correlated with disease duration and functional status. These data suggest that quantitative MRI of the SC may be a useful biomarker in the disease.

Serum chemokine levels as prognostic markers in patients with early systemic sclerosis: a multicenter, prospective, observational study

Objective To assess the utility of serum chemokine levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease.Methods Seventy Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicenter, observational study. Concentrations of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in serum samples from all patients were measured using cytometric beads array. In 33 patients, chemokine levels were measured each year for 4 years. The ability of baseline chemokine levels to predict changes in clinical features were evaluated statistically by multiple regression analysis.Results At their first visit, serum levels of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 were significantly elevated in patients with SSc compared with healthy controls. There were significant associations between CCL2 and CXCL8 levels and between CXCL9 and CXCL10 levels in patients. The initial serum CXCL8 levels were significantly associated with the HAQ-DI at the fourth year while the %VC of baseline tended to be negatively associated with HAQ-DI at the fourth year. Initial chemokine levels were not associated with other clinical features including skin thickness score and the respiratory function.Conclusion Serum CXCL8 level may serve as a prognostic indicator of the physical dysfunction in SSc. Further longitudinal studies of larger populations are needed to confirm these findings.

Protein kinase C-η polymorphism rs2230500 does not confer disease susceptibility to multiple sclerosis or neuromyelitis optica

Objectives To determine whether the non-synonymous 1425G/A polymorphism (rs2230500), an Asian-specific single nucleotide polymorphism that increases the kinase activity and affects the function of immune cells, of the protein kinase C-η gene (PRKCH) confers the risk of developing idiopathic demyelinating diseases of the central nervous system in a Japanese population. Methods Blood samples were collected from 96 multiple sclerosis (MS) patients, 52 neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) patients and 151 healthy controls. The polymorphism rs2230500 was genotyped by sequencing. Results No significant association was observed between the PRKCH rs2230500 polymorphism and the risk of either MS or NMO/NMOSD. Clinical characteristics were also unaffected by the rs2230500 status. Conclusions Although the possibility that PRKCH has some effect on MS and NMO/NMOSD risk cannot be completely excluded because of the small study sample size, the polymorphism rs2230500 did not appear to confer disease susceptibility to MS or NMO/NMOSD in this Japanese population.

The Effects of Human Wild-Type and Fals Mutant L144P SOD1 on Non-Vascular Smooth Muscle Contractions / EFEKTI HUMANE NORMALNE I FALS MUTIRANE L144P SOD1 NA NEVASKULARNE KONTRAKCIJE GLATKIH MIŠIĆA

Summary Background: Mutated copper, zinc-containing superoxide dismutase (SOD1) may self-aggregate, an event that could also be an initial cause of motor neuron malfunction leading to disease onset. The effects of human mutated SOD1 pro- tein from the blood of familial amyotrophic lateral sclerosis (FALS) patients bearing Leu144Phe (L144F) mutation were compared to wild-type (WT) human SOD1 derived from healthy examinees, for enzymatic activity and the effects on isometric contractions of non-vascular smooth muscle. Methods: We isolated WT and L144F SOD1 enzymes from eight patients with FALS, L144F mutation in exon 5 and eight healthy controls. We then investigated SOD1 activities in the obtained samples by the adrenaline method and pro- filed them electrophoretically. Finally, we applied WT and L144F SOD1 on the isolated rat uterus. Results: L144F SOD1 showed lower superoxide-dismutating activity compared to WT human SOD1. We found that, in contrast to WT human SOD1, mutated L144F does not induce smooth muscle relaxation. Conclusions: Our data suggest that the lack of relaxation of muscle tonus in the presence of mutated SOD1 may have pathogenic feedback effects in FALS.

Population pharmacokinetics and pharmacodynamics of dalfampridine-ER in healthy volunteers and in patients with multiple sclerosis

Objective:Using data pooled from several studies of dalfampridine extended release (ER), a population pharmacokinetic model was developed for the purposes of characterizing the population pharmacokinetics and pharmacodynamics of dalfampridine-ER with respect to variability in pharmacokinetics, covariates affecting the pharmacokinetics, and whether the current therapeutic dosage represents an optimal dosage. Studies were conducted in healthy volunteers and multiple sclerosis (MS) patients over the course of development and registration of dalfampridine extended release tablets (dalfampridine-ER [Ampyra]; prolonged-, modified- or sustained-release fampridine [Fampyra] in some countries).Methods:The model used to best describe the population pharmacokinetics of dalfampridine-ER was an open, one-compartment model with first-order absorption, first-order elimination and an absorption lag time.Results:The population median estimated oral clearance was 36 L/h for a 50-year-old woman with a creatinine clearance of 105 mL/min and 42 L/h for a comparable man. The typical volume of distribution was 304 L for women and 403 L for men. The estimated absorption rate constant was 1.22 hours−1 in the fasted state and 2.22 hours−1 when given with food. The covariates identified as having a significant effect (p < 0.01) on model fit were food and gender on absorption rate, and gender, age and creatinine clearance on oral clearance. Only creatinine clearance and age are of clinical relevance. Concomitant medications did not affect any of the parameters in the model. Exposure–response relationships for both efficacy and safety were consistent with what has been observed in clinical trials. Limitations of this study include some reliance on unpublished data, and the limited effectiveness of the model for determining the likelihood of the efficacy and safety of dalfampridine-ER in clinical practice.Conclusions:The approved therapeutic dosage regimen of dalfampridine-ER 10 mg twice daily was identified as the optimum dosing regimen based on model-predicted exposure response relationships for efficacy and adverse events. A limitation of this study is the limited effectiveness of the models used to predict long-term efficacy and safety of dalfampridine-ER in clinical use.

The relationship between the internal capsule DTI parameters and cognition in relapsing remitting multiple sclerosis (RR MS) patients

The relationship between the internal capsule DTI parameters and cognition in relapsing remitting multiple sclerosis (RR MS) patients

The value of pattern capillary changes and antibodies to predict the development of systemic sclerosis in patients with primary Raynaud’s phenomenon

The aim of this study is to assess the prognostic value of major provisional criteria for the development of systemic sclerosis (SSc) in primary Raynaud's phenomenon (RP) patients. We retrospectively studied the chart of 497 patients with primary RP in whom anticentromere (ACA) and antitopoisomerase I (ATA) antibodies tests and a capillary reading were available. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratios (LHR+), negative likelihood ratios (LHR-), odds ratio (OR), and area under the receiver operating characteristics curve (AUC) of those criteria were assessed to predict the development of SSc. During the average follow-up of 2.3 ± 1.9 years, 159 (32 %) patients evolved to SSc, 245 (49.3 %) evolved to other connective tissue diseases, and 93 (18.7 %) patients did not progress. The SSc pattern predicted SSc satisfactorily (LHR+ 4.12, LHR- 0.07, OR 63, AUC 0.819; P < 0.001). ACA were not significantly associated with the development of SSc (LHR+ 1.19, LHR- 0.9, OR 1.32, AUC 0.538, P = 0.156). ATA were significantly associated with the development of SSc (LHR+ 9.32, LHR- 0.67, OR 15.13, AUC 0.777; P < 0.001). Both SSc pattern and ACA or ATA were significantly associated with the development of SSc (LHR+ 2.98, LHR- 0.70, OR 4.2, AUC 0.674; P < 0.001 vs. LHR+ 16, LHR- 0.68, OR 24, AUC 0.819; P < 0.001, respectively). SSc pattern or ATA as independent risk factors, as well as following two parameters together (SSc pattern and ATA or SSc pattern and ACA) were good predictors for the development of SSc.