R Scorza

University of Catania, Catania, Sicily, Italy

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Publications (217)630.48 Total impact

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    ABSTRACT: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes.
    Annals of the rheumatic diseases. 10/2014;
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    ABSTRACT: Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases we performed a pan-meta-analysis of two genome-wide association studies (GWAS) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21,109 (6,835 cases and 14,274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319 L (P=3.31x10−11, OR=1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P=3.27x10−11, OR=1.20) and JAZF1 (P=1.11x10−8, OR=1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319 L was overexpressed in peripheral blood cells of SSc and SLE patients compared to healthy controls. With these, we add three (KIAA0319 L, PXK and JAZF1) and one (KIAA0319 L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.
    Human Molecular Genetics 05/2013; 22(19):4021-4029. · 7.69 Impact Factor
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    ABSTRACT: A case control study to evaluate the possible influence of FOXP3 polymorphisms (rs3761548 and rs2280883) in the susceptibility of systemic sclerosis in an Italian Caucasian population. Subgroup analysis was also performed to test association between these SNPs and specific disease phenotypes. The study groups consisted of 467 individuals: 228 patients (194 with limited cutaneous form and 34 with diffuse cutaneous form of the disease) and 239 healthy control subjects. Genotyping was performed by high resolution melting analysis. Genotype distribution and allele frequency of the FOXP3 polymorphisms were analyzed statistically, using χ(2) or Fisher exact test. Single-marker analysis of allelic and genotype frequencies revealed that SNP rs3761548 was not associated with systemic sclerosis susceptibility. Analysis of genotype and allele distributions of the rs2280883 genetic variant was associated, only in female subjects with systemic sclerosis, its limited subtype, and anti-centromere autoantibodies. Although these findings require replication in a larger set and other populations, FOXP3 rs2280883 may represent a novel susceptibility locus for systemic sclerosis in female subjects.
    Immunology letters 05/2013; · 2.91 Impact Factor
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    ABSTRACT: BACKGROUND: To determine the usefulness of Ca 15.3 as a candidate biomarker in systemic sclerosis (SSc) patients with interstitial lung disease (ILD). METHODS: Two-hundred-twenty-one SSc patients with Ca 15.3 determinations were considered; 168 had evidence of interstitial lung involvement on high-resolution computed tomography (HRCT); digitalized scans were available for scoring in 84 subjects. Discrimination between patients with or without ILD, was assessed by receiving operating characteristics (ROC) analysis; correlations between HRCT scores and Ca 15.3 were performed. Survival and serial pulmonary function tasting (PFT) data were used for prognostication. RESULTS: Ca 15.3 serum levels strongly correlated with HRCT scores (r=0.734, p<0.0001) which were predictors of survival at the 20% threshold (p=3.1∗10(-4)). Ca 15.3 had an area under ROC to detect the meaningful 20% fibrosis extent equal to 0.927 and abnormal Ca 15.3 values were capable of differentiating between patients at hi- or low-risk for progression in the group with undetermined disease extent (HR=3.209, confidence interval [CI95]=1.56-6.602, p=0.002). Ca 15.3 outperformed other PFT measures in providing a separation of survival estimates where HRCT scans are unavailable. The combined use of HRCT scores and Ca 15.3 in SSc-ILD patients was more discriminatory (HR=4.824, CI95=2.612-8.912, p<0.0001) than the staging system based on HRCT scores plus FVC (HR=2.657, CI95=1.703-4.147, p<0.0001) and characterized by lower prediction errors (0.2134 vs 0.2234). CONCLUSION: Ca 15.3 is a rapid and inexpensive candidate biomarker for SSc-ILD being proportional to the extent of lung injury and specific and sensitive in assessing meaningful extents of the disease with prognostic significance.
    European Journal of Internal Medicine 05/2013; · 2.30 Impact Factor
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    ABSTRACT: PURPOSE: To study, by a new, integrated, laser scanning confocal microscopy approach, the ocular surface morpho-functional unit in patients with primary Sjogren syndrome (SSI), non-Sjogren syndrome dry eye (non-SSDE), and meibomian gland disease (MGD). METHODS: Patients and age- and sex-matched control subjects (N = 60; 15 each) were consecutively enrolled in a prospective case-control study. Laser scanning confocal microscopy was used to obtain simultaneous optical sampling of the ocular surface components: cornea, bulbar and tarsal conjunctiva, MGs, and eyelid margin. RESULTS: For all superficial epithelia, except eyelid margins, there were reduced cell densities in each group compared with that in controls (p < 0.001). The lowest cell densities were in the SSI group (p < 0.001). Eyelid margin superficial cell density was decreased only in MGD (p < 0.001). Basal epithelial cell density at the corneal apex was increased in both SSI and non-SSDE compared with that in controls (p < 0.01). In the conjunctiva, it was decreased in each group compared with that in controls (p < 0.01). Subbasal dendritic cell density was significantly increased in both SSI and MGD compared with that in controls (p < 0.01). Conjunctival inflammatory cell density and MG inflammation were increased in each group compared with those in controls (p < 0.001), with the highest values in SSI. Subbasal nerve plexi had fewer fibers and higher bead density in each group compared with those in controls (p < 0.001). There was increased tortuosity in both SSI and MGD (p < 0.001). Patients with MGD had the lowest MG acinar density, the largest diameter of acini and acinar orifices, and the highest secretion reflectivity (p < 0.001). CONCLUSIONS: Laser scanning confocal microscopy can provide an in vivo, noninvasive, high-resolution overview of the ocular surface morpho-funcional unit. This confocal integrated approach may be useful in both research and clinical settings.
    Optometry and vision science: official publication of the American Academy of Optometry 05/2013; · 1.53 Impact Factor
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    ABSTRACT: Objective Pulmonary arterial hypertension (PAH), a common complication of limited cutaneous systemic sclerosis (lcSSc), is associated with alterations of markers of inflammation and vascular damage in peripheral blood mononuclear cells (PBMCs). Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been implicated in autoimmune and inflammatory diseases. The goal of this study was to assess whether markers of ER stress and the UPR are present in PBMCs from lcSSc patients with PAH. MethodsPBMCs were purified from 36 healthy controls, 32 lcSSc patients with PAH, and 34 lcSSc patients without PAH. Gene expression in healthy control PBMCs stimulated with thapsigargin was analyzed by DNA microarray. Genes were validated by quantitative real-time reverse transcription–polymerase chain reaction in PBMCs from healthy controls and lcSSc patients. ResultsSeveral ER stress/UPR genes, including BiP, activating transcription factor 4 (ATF-4), ATF-6, and a spliced form of X-box binding protein 1, were up-regulated in PBMCs from lcSSc patients, with the highest levels in patients with PAH. Thapsigargin up-regulated heat-shock proteins (HSPs) and interferon (IFN)–regulated genes in PBMCs from healthy controls. Selected HSP genes (particularly DnaJB1) and IFN-related genes were also found at significantly elevated levels in PBMCs from lcSSc patients, while IFN regulatory factor 4 expression was significantly decreased. There was a positive correlation between DnaJB1 and severity of PAH (measured by pulmonary artery pressure) (r = 0.56, P < 0.05) and between ER stress markers and interleukin-6 levels (r = 0.53, P < 0.0001) in PBMCs from lcSSc patients. Conclusion This study demonstrates an association between select ER stress/UPR markers and lcSSc with PAH, suggesting that ER stress and the UPR may contribute to the altered function of circulating immune cells in lcSSc.
    Arthritis & Rheumatology 05/2013; 65(5). · 7.48 Impact Factor
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    ABSTRACT: TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE.
    BioMed research international. 01/2013; 2013:471703.
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    ABSTRACT: Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10(-8), OR = 1.22, CI 95% = 1.14-1.30; rs2004640: P = 4.60×10(-7), OR = 0.84, CI 95% = 0.78-0.90; rs10488631: P = 7.53×10(-20), OR = 1.63, CI 95% = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10(-22), OR = 1.75, CI 95% = 1.56-1.97) better explained the observed association (likelihood P-value = 1.48×10(-4)), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.
    PLoS ONE 01/2013; 8(1):e54419. · 3.53 Impact Factor
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    ABSTRACT: Endothelin 1 (ET-1) is a key regulator of vascular homeostasis. We have recently reported that the presence of Human antigen class I, HLA-B35, contributes to human dermal microvascular endothelial cell (HDMEC) dysfunction by upregulating ET-1 and proinflammatory genes. Likewise, a Toll-like receptor 3 (TLR3) ligand, Poly(I:C), was shown to induce ET-1 expression in HDMECs. The goal of this study was to determine the molecular mechanism of ET-1 induction by these two agonists. Because HLA-B35 expression correlated with induction of Binding Immunoglobulin Protein (BiP/GRP78) and several heat shock proteins, we first focused on ER stress and unfolded protein response (UPR) as possible mediators of this response. ER stress inducer, Thapsigargin (TG), HLA-B35, and Poly(I:C) induced ET-1 expression with similar potency in HDMECs. TG and HLA-B35 activated the PERK/eIF2α/ATF4 branch of the UPR and modestly increased the spliced variant of XBP1, but did not affect the ATF6 pathway. Poly(I:C) also activated eIF2α/ATF4 in a protein kinase R (PKR)-dependent manner. Depletion of ATF4 decreased basal expression levels of ET-1 mRNA and protein, and completely prevented upregulation of ET-1 by all three agonists. Additional experiments have demonstrated that the JNK and NF-κB pathways are also required for ET-1 upregulation by these agonists. Formation of the ATF4/c-JUN complex, but not the ATF4/NF-κB complex was increased in the agonist treated cells. The functional role of c-JUN in responses to HLA-B35 and Poly(I:C) was further confirmed in ET-1 promoter assays. This study identified ATF4 as a novel activator of the ET-1 gene. The ER stress/UPR and TLR3 pathways converge on eIF2α/ATF4 during activation of endothelial cells.
    PLoS ONE 01/2013; 8(2):e56123. · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVES: Scleroderma renal crisis (SRC) is a relative rare yet dramatic event in the history of systemic sclerosis (SSc). Several factors that may precipitate or protect from the development of SRC have been described in previous case-control studies. To date, no attempt has been made to evaluate these factors in an observational fashion. METHODS: Retrospective data from 410 SSc patients with disease duration <5 years at referral were evaluated in an observational fashion for the development of hypertensive or normotensive SRC within 5 years from the first visit at our centre. Baseline characteristics as well as the use of steroids or dhiydropyridine calcium-channel blockers (CCB) were analysed via the Cox regression method with time-dependent covariates. RESULTS: In the multivariate model the diffuse subset the disease (HR=5.728 CI95=2.199-14.918, p<0.001) and the use of prednisone (HR=1.015, CI95=1.004-1.026, p=0.006) resulted to be predictors for the development of SRC, with a risk to develop SRC increased by 1.5% for every mg of prednisone/day consumed the trimester prior SRC. Contrariwise, the risk to develop SRC was highly reduced in those who were prescribed CCBs (HR=0.094, CI95=0.038-0.236, p<0.001). CONCLUSIONS: Steroids exhibits a weak effect on the risk to progress toward SRC in our case series, whilst dhyidrophyridines CCB appeared to be protective against that. Further larger prospective studies are warranted to better define the role of CCB in this setting or as a background therapy for SSc.
    Clinical and experimental rheumatology 12/2012; · 2.66 Impact Factor
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    ABSTRACT: OBJECTIVE: The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). PATIENTS AND METHODS: The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays. RESULTS: We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (p(c)=6.6E-4 and p(c)=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (p(c)=1.7E-03 and p(c)=8E-4, respectively). CONCLUSIONS: These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.
    Annals of the rheumatic diseases 11/2012; · 8.11 Impact Factor
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    Human Immunology 09/2012; 73(9):950-3. · 2.30 Impact Factor
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    ABSTRACT: INTRODUCTION: A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. METHODS: 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. RESULTS: Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 p(MH)=1.94×10(-4), OR 1.19; rs4958881 p(MH)=3.26×10(-5), OR 1.19; rs3792783 p(MH)=2.16×10(-4), OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets. CONCLUSIONS: These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor.
    Annals of the rheumatic diseases 08/2012; · 8.11 Impact Factor
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    ABSTRACT: A candidate gene for TIMP-1 gene located on the X-chromosome (rs4898) was selected for a control case study to investigate a possible association of this SNP with the susceptibility to systemic sclerosis and its digit ulcer manifestation. A total of 461 individuals of Italian Caucasian origin (228 SSc patients and 233 healthy control subjects) were genotyped for TIMP-1 +372 T/C single nucleotide polymorphism rs4898. Subgroups were analyzed according to the presence or absence of digital ulcers. The CC genotype and C allele frequencies were significantly lower in female SSc patients than in controls (OR 0.53, CI 0.29-0.96, p=0.03 and OR 0.72, CI 0.53-0.98 p=0.04, respectively). CC genotypes frequency was lower also in female patients with ulcers than those without ulcers (OR 0.37, CI 0.14-1.00, p=0.03). Furthermore, CC genotype and C allele frequencies were lower also in female patients with ulcers in comparison to female healthy control subjects (OR 0.27, CI 0.10-0.70, p=0.004; OR 0.60, CI 0.40-0.89, p=0.01, respectively). The TIMP-1 rs4898 polymorphism may play a protective role in the susceptibility to SSC in females, and in particular to digital ulcer formation.
    Human immunology 07/2012; 73(9):950-3. · 2.55 Impact Factor
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    ABSTRACT: Systemic sclerosis (SSc) is a rare disease requiring multicentre collaboration to reveal comprehensive details of disease-related causes for morbidity and mortality. The European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) group initiated a database to prospectively gather key data of patients with SSc using a minimal essential dataset that was reorganised in 2008 introducing new items. Baseline visit data of patients who were registered between 2004 and 2011 were analysed using descriptive statistics. In June 2011, 7655 patients (2838 with diffuse cutaneous (dc) and 4481 with limited cutaneous (lc) SSc who fulfilled the American College of Rheumatology diagnostic criteria had been registered in 174 centres, mainly European. The most prominent hallmarks of disease were Raynaud's phenomenon (96.3%), antinuclear antibodies (93.4%) and a typical capillaroscopic pattern (90.9%). Scleroderma was more common on fingers and hands than on any other part of the skin. Proton pump inhibitors (65.2%), calcium channel blockers (52.7%), and corticosteroids (45.3%) were most often prescribed. Among the immunosuppressant agents, cyclophosphamide was used more often in dcSSc than in lcSSc. The EUSTAR database provides an abundance of information on the true clinical face of SSc that will be helpful in improving the classification of SSc and its subsets and for developing more specific therapeutic recommendations.
    Annals of the rheumatic diseases 05/2012; 71(8):1355-60. · 8.11 Impact Factor
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    ABSTRACT: 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.
    Genes and immunity 05/2012; 13(6):458-60. · 4.22 Impact Factor
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    ABSTRACT: Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective tissue; influenced by genetic and environmental components. Recently, we performed the first successful genome-wide association study (GWAS) of SSc. Here, we perform a large replication study to better dissect the genetic component of SSc. We selected 768 polymorphisms from the previous GWAS and genotyped them in seven replication cohorts from Europe. Overall significance was calculated for replicated significant SNPs by meta-analysis of the replication cohorts and replication-GWAS cohorts (3237 cases and 6097 controls). Six SNPs in regions not previously associated with SSc were selected for validation in another five independent cohorts, up to a total of 5270 SSc patients and 8326 controls. We found evidence for replication and overall genome-wide significance for one novel SSc genetic risk locus: CSK [P-value = 5.04 × 10(-12), odds ratio (OR) = 1.20]. Additionally, we found suggestive association in the loci PSD3 (P-value = 3.18 × 10(-7), OR = 1.36) and NFKB1 (P-value = 1.03 × 10(-6), OR = 1.14). Additionally, we strengthened the evidence for previously confirmed associations. This study significantly increases the number of known putative genetic risk factors for SSc, including the genes CSK, PSD3 and NFKB1, and further confirms six previously described ones.
    Human Molecular Genetics 03/2012; 21(12):2825-35. · 7.69 Impact Factor
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    ABSTRACT: To determine whether the allelic frequency variation of the HS1.2 enhancer of the immunoglobulin heavy chain (IgH) 3' regulatory region (3'RR-1) locus represents a risk factor for systemic lupus erythematosus (SLE) and to identify a possible functional difference in the two most frequent alleles (*1 and *2) in binding nuclear factor- κB (NF-κB) and Sp1. The frequency of the enhancer HS1.2 alleles was determined in two cohorts of patients with SLE (n=293) and in 1185 controls. Electrophoretic mobility shift assays (EMSA) were carried out with B cell nuclear extracts with different probes of HS1.2 alleles *1 and *2 to map the consensus binding sites of the nuclear factors. A confirmatory cohort of 121 patients with SLE was also included. The frequency of allele *2 of the HS1.2 enhancer was significantly increased in patients with SLE compared with controls (OR 1.60, 95% CI 1.33 to 1.92, p<0.001). EMSA experiments showed the presence of the Sp1 binding site in both alleles whereas only allele *2 carried the consensus for the NF-κB factor. The presence versus absence of allele *2 in patients with SLE correlated with a higher concentration of IgM levels and with the expression of B cell activating factor receptor (BAFF-R). The increased frequency of allele *2 in patients with SLE identifies a new genetic risk factor for SLE. A possible biological effect of the polymorphism could be the difference observed in the localisation of an NF-κB binding site which is specific for allele *2 and absent in allele *1. These observations suggest a functional effect of the HS1.2 enhancer in this disease.
    Annals of the rheumatic diseases 01/2012; 71(8):1309-15. · 8.11 Impact Factor
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    ABSTRACT: To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2-193 months). SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (<34 weeks of gestation) (10% versus 5%), intrauterine growth restriction (6% versus 1%), and babies with very-low birth weight (5% versus 1%). Results of multivariable analysis showed that corticosteroid use was associated with preterm deliveries (odds ratio [OR] 3.63, 95% confidence interval [95% CI] 1.12-11.78), whereas the use of folic acid (OR 0.30, 95% CI 0.10-0.91) and presence of anti-Scl-70 antibodies (OR 0.26, 95% CI 0.08-0.85) were protective. The disease remained stable in most SSc patients, but there were 4 cases of progression of disease within 1 year from delivery, all in anti-Scl-70 antibody-positive women, 3 of whom had a disease duration of <3 years. Women with SSc can have successful pregnancies, but they have a higher-than-normal risk of preterm delivery, intrauterine growth restriction, and babies with very-low birth weight. Progression of the disease during or after pregnancy is rare, but possible. High-risk multidisciplinary management should be standard for these patients, and pregnancy should be avoided in women with severe organ damage and postponed in women with SSc of recent onset, particularly if the patient is positive for anti-Scl-70 antibodies.
    Arthritis & Rheumatology 12/2011; 64(6):1970-7. · 7.48 Impact Factor

Publication Stats

2k Citations
630.48 Total Impact Points


  • 2006–2013
    • University of Catania
      • Department of Biomedical Sciences (BIOMED)
      Catania, Sicily, Italy
  • 2001–2013
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      • • Regional Reference Centre for Systemic Autoimmune Diseases
      • • Allergology and Clinical Immunology
      • • Internal Medicine 3
      Milano, Lombardy, Italy
  • 2011–2012
    • Spanish National Research Council
      • Institute of Parasitology and Biomedicine "López-Neyra"
      Madrid, Madrid, Spain
    • University of Texas MD Anderson Cancer Center
      • Department of Epidemiology
      Houston, TX, United States
  • 1987–2012
    • University of Milan
      • • Department of Health Science - DISS
      • • Department of Internal Medicine
      Milano, Lombardy, Italy
  • 2010
    • Azienda Ospedaliera Niguarda Ca' Granda
      Milano, Lombardy, Italy
    • Boston University
      • Arthritis Center
      Boston, MA, United States
  • 2007
    • University of Santiago de Compostela
      Santiago, Galicia, Spain
  • 2005
    • Amedeo Avogadro University of Eastern Piedmont
      • Interdisciplinary Research Center of Autoimmune Diseases IRCAD
      Alessandria, Piedmont, Italy
  • 2003
    • Azienda Ospedaliera San Camillo Forlanini
      Roma, Latium, Italy
    • Azienda Ospedaliera San Paolo - Polo Universitario
      Milano, Lombardy, Italy
  • 2002
    • Università degli Studi dell'Insubria
      Varese, Lombardy, Italy
  • 2000
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 1998–1999
    • Università degli Studi del Sannio
      Benevento, Campania, Italy
  • 1996
    • Università degli Studi di Torino
      • Dipartimento di Scienze Mediche
      Torino, Piedmont, Italy