Quantification of Antifibrillarin (anti-U3 RNP) Antibodies: A New Insight for Patients with Systemic Sclerosis

Background: The detection of additional autoantibodies is of great concern in systemic sclerosis (SSc) when those included in the ACR/EULAR classification are negative. In this context, the interest of antifibrillarin (anti-U3RNP) autoantibodies (AFAs) in the routine evaluation of SSc remains unclear. We aimed to assess the relevance of AFAs and their clinical association in SSc patients. Methods: In a multicenter observational retrospective study, we collected immunological and clinical data associated with AFA positivity in SSc (n = 42) and non-SSc patients (n = 13). Patients with SSc negative for AFAs (n = 83) were considered as a control group. AFAs were detected by indirect immunofluorescence (IIF) using HEp-2 cells, EliA or immunoblot techniques. Results: We confirmed a typical nuclear IIF pattern and showed that AFAs are mostly exclusive towards SSc conventional autoantibodies. Although also observed in non-SSc patients, high levels of AFAs with the ELiA technique allowed the diagnosis of SSc. Compared to AFA-negative SSc patients, AFA-positive SSc patients more frequently exhibited visceral involvements. They more frequently suffered from the diffuse cutaneous form and had a higher global severity of the disease. Conclusions: We demonstrate the usefulness of quantifying AFAs in the immunological exploration of SSc, especially when patients are seronegative for SSc conventional autoantibodies and display a typical IIF pattern. AFAs might constitute an interesting marker of SSc severity.

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Endothelin-1 Levels in Scleroderma Patients: A Pilot Study

ISRN Dermatology ◽

10.1155/2013/125632 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 8

Author(s):

Emanuele Cozzani ◽

Sanja Javor ◽

Erika Laborai ◽

Massimo Drosera ◽

Aurora Parodi

Keyword(s):

Retrospective Study ◽

Systemic Sclerosis ◽

Pilot Study ◽

Serum Levels ◽

Vascular Wall ◽

Digital Ulcers ◽

Normal Range ◽

Endothelin 1 ◽

Treatment And Prevention ◽

Severity Of The Disease

Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor, which mediates vascular wall cells proliferation, fibrosis, and inflammation through two types of ET-1 receptors (ET-A and ET-B). In our retrospective study the serum levels of ET-1 in 18 systemic sclerosis (SSc) patients with and without digital ulcers (DUs) were assessed to observe possible correlation between the levels of ET-1, the evolution of SSc, and the therapy with an ET-1 antagonist (bosentan). In all our patients, the levels of ET-1 were found higher than normal range and correlate with the severity of the disease. Furthermore we also observed that in patients without DUs the levels of ET-1 were higher and did not correlate with new DUs development. In conclusion, the levels of ET-1 in our studied patients do not correlate with the possible development of DUs. The reduction of ET-1 levels in DUs patients in therapy with bosentan confirms the efficacy of this molecule both for treatment and prevention of digital ulcers. The inhibition of ET-A receptor by its antagonist may activate the opposite ET-B receptors, with well-known function ET-1 degradation and reducing of ET-1 serum level as confirmed in our pilot study.

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Haemophilia Registry of the Medical Committee of the Swiss Haemophilia Society

Hämostaseologie ◽

10.1055/s-0037-1617205 ◽

2009 ◽

Vol 29 (S 01) ◽

pp. S16-S18 ◽

Cited By ~ 2

Author(s):

B. Brand ◽

N. von der Weid

Keyword(s):

Quality Control ◽

Infectious Diseases ◽

Mutation Analysis ◽

Clinical Data ◽

Age Groups ◽

Treatment Modalities ◽

Global Survey ◽

On Demand ◽

Per Capita ◽

Severity Of The Disease

SummaryThe Swiss Haemophilia Registry of the Medical Committee of the Swiss Haemophilia Society was established in 2000. Primarily it bears epidemiological and basic clinical data (incidence, type and severity of the disease, age groups, centres, mortality). Two thirds of the questions of the WFH Global Survey can be answered, especially those concerning use of concentrates (global, per capita) and treatment modalities (on-demand versus prophylactic regimens). Moreover, the registry is an important tool for quality control of the haemophilia treatment centres.There are no informations about infectious diseases like hepatitis or HIV, due to non-anonymisation of the data. We plan to incorporate the results of the mutation analysis in the future.

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Association of Serum Homocysteine Level and Interstitial Lung Disease in Systemic Sclerosis: A Case-control Study

Current Rheumatology Reviews ◽

10.2174/1573397114666180628162907 ◽

2018 ◽

Vol 15 (1) ◽

pp. 74-78

Author(s):

Mohammadali Nazarinia ◽

Asghar Zare ◽

Mohammad javad Fallahi ◽

Mesbah Shams

Keyword(s):

Systemic Sclerosis ◽

Healthy Subjects ◽

Case Control Study ◽

Homocysteine Level ◽

Case Control ◽

Control Group ◽

Lung Involvement ◽

Serum Homocysteine ◽

The Mean ◽

Control Study

Background:Systemic sclerosis is a disorder of connective tissue with unknown cause, affecting the skin and internal organs, characterized by fibrotic changes.Objective:To determine the correlation between serum homocysteine level and interstitial lung involvement in systemic sclerosis. </P><P> Materials and Methods: In this case – control study, 59 patients who fulfilled the ACR/EULAR classification criteria for systemic sclerosis and were referred to Hafez Hospital of Shiraz, Iran, were included as the case group. Fifty nine healthy subjects were involved as the control group. Patients were divided into two groups based on interstitial lung involvement and two subtypes, diffuse and limited type. Serum homocysteine, vitamin B12, and folate levels compared between the controls, and cases groups.Results:Of 59 case and control group, 53 (%89.8) were female and the mean age did not differ in both groups (P=0.929). Thirty five (%59.3) patients had interstitial lung involvement and 38(%64.4) had diffuse cutaneous systemic sclerosis. The mean serum homocysteine level was 13.9±6.3 µmol/L in the case and 13.7±9.2 µmol/L in the control group (P=0.86). The mean serum homocysteine level did not differ between the patients with and without interstitial lung involvement (P=0.52). The patients with lung involvement was older than those without lung involvement (P=0.004). Lung disease was more common in diffuse type (P=0.014).Conclusion:In our study, serum homocysteine level did not differ between the patients and healthy subjects. Also, there was no correlation between serum homocysteine level and lung involvement, but lung involvement was more common in older patients and also diffuse subtype.

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Combining multi-antigenic immunodot with indirect immunofluorescence on HEp-2 cells improves the diagnosis of systemic sclerosis

Clinical Immunology ◽

10.1016/j.clim.2021.108774 ◽

2021 ◽

pp. 108774

Author(s):

Bost Chloé ◽

Fortenfant Françoise ◽

Antoine Blancher ◽

Pugnet Grégory ◽

Renaudineau Yves

Keyword(s):

Systemic Sclerosis ◽

Indirect Immunofluorescence

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Role and effectiveness of complex and supervised rehabilitation on overall and hand function in systemic sclerosis patients—one-year follow-up study

Scientific Reports ◽

10.1038/s41598-021-94549-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Michał Waszczykowski ◽

Bożena Dziankowska-Bartkowiak ◽

Michał Podgórski ◽

Jarosław Fabiś ◽

Arleta Waszczykowska

Keyword(s):

Systemic Sclerosis ◽

Hand Function ◽

Exercise Program ◽

Rehabilitation Program ◽

Long Term Results ◽

Home Exercise ◽

Control Group ◽

Study Group

AbstractThe aim of this study was to estimate the long-term results of complex and supervised rehabilitation of the hands in systemic sclerosis (SSc) patients. Fifty-one patients were enrolled in this study: 27 patients (study group) were treated with a 4-week complex, supervised rehabilitation protocol. The control group of 24 patients was prescribed a home exercise program alone. Both groups were evaluated at baseline and after 1-, 3-, 6-, and 12-months of follow-up with the Disability of the Arm, Shoulder and Hand Questionnaire (DAHS) as the primary outcome, pain (VAS—visual analog scale), Cochin Hand Function Scale (CHFS), Health Assessment Questionnaire Disability Index (HAQ-DI), Scleroderma-HAQ (SHAQ), range of motion (d-FTP—delta finger to palm, Kapandji finger opposition test) and hand grip and pinch as the secondary outcomes. Only the study group showed significant improvements in the DASH, VAS, CHFS and SHAQ after 1, 3 and 6 months of follow-up (P = 0.0001). Additionally, moderate correlations between the DASH, CHFS and SHAQ (R = 0.7203; R = 0.6788; P = 0.0001) were found. Complex, supervised rehabilitation improves hand and overall function in SSc patients up to 6 months after the treatment but not in the long term. The regular repetition of this rehabilitation program should be recommended every 3–6 months to maintain better hand and overall function.

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Radiological Parameters Review for Choanal Atresia

Pediatric Reports ◽

10.3390/pediatric13020038 ◽

2021 ◽

Vol 13 (2) ◽

pp. 302-311

Author(s):

Daniela Messineo ◽

Maryia Chernikava ◽

Valeria Pasquali ◽

Serena Bertin ◽

Mario Ciotti ◽

...

Keyword(s):

Retrospective Study ◽

High Resolution ◽

Surgical Approach ◽

Choanal Atresia ◽

Point Of View ◽

Control Group ◽

Study Group ◽

Control Groups ◽

Imaging Parameters ◽

Multiplanar Imaging

(1) Background: The study aims to identify which imaging parameters are necessary for a new correct surgical approach in the study of choanal atresia, and which anatomical findings are essential for correct planning of endoscopic treatment in choanal atresia. (2) Methods: In this retrospective study, 19 patients with choanal atresia had high-resolution multiplanar imaging (14 cases aged ≤1 year and 5 cases aged 1 to 3 years) and 35 patients in the control group similarly distributed by age. Fourteen variables, the most relevant from a surgical point of view, were selected and measured. A comparison was made between the averages of the study group and the different control groups, either directly observed or selected from the literature, using Pearson’s correlation. (3) Results: In 14 out of 26 cases, the differences were statistically significant. There was a correlation between the structures assessed, such as choanal height, rostrum height, and age. (4) Conclusions: Thanks to volumetric reformatting, this work identified and provided the clinician with useful information that helped choose the correct surgical approach. Furthermore, it focused on which imaging parameters are necessary to improve the planning of the surgical correction of choanal atresia.

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SAT0320 BONE MINERAL DENSITY AND FRACTURE RISK IN A COHORT OF PORTUGUESE SYSTEMIC SCLEROSIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2752 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1105.1-1106

Author(s):

S. Garcia ◽

B. M. Fernandes ◽

S. Ganhão ◽

M. Rato ◽

F. Pinheiro ◽

...

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Systemic Sclerosis ◽

Hip Fracture ◽

Fracture Risk ◽

Vitamin D Insufficiency ◽

Spine Fractures ◽

Mineral Density ◽

Portuguese Population ◽

Cutaneous Form

Background:Although poorly understood, patients with Systemic Sclerosis (SSc) seem to have higher prevalence of low bone mineral density (BMD) and an increased spine fracture risk.Objectives:We aim to determine, by conventional densitometry (DXA) and using the fracture risk assessment tool (FRAX), the prevalence of low BMD and the fracture risk, respectively, in our SSc cohort and its potential determinants.Methods:Observational transversal study was performed including consecutive patients with the diagnosis of SSc. We collected data regarding demographics, BMD (lumbar spine and femoral neck) and occurrence of fracture. Ten-year risk of osteoporotic fracture was estimated using FRAXv4.1with the Portuguese population reference. Statistical analysis was performed using SPSS 23.0; p<0.01 was considered statistically significant.Results:Median age of patients (n=97) was 62 years old [56, 70], 88.7% females (n=86). Seventy-eight patients (80.4%) had limited cutaneous form, 5 (5.2%) presented a diffuse cutaneous form and 13 (13.4%) an overlap syndrome. Regarding clinical features: digital ulcers in 30 patients (30.9%), interstitial lung disease (ILD) in 16 (6.5%), gastrointestinal involvement in 16 (16.5%), miositis in 4 (4.1%) and pulmonary arterial hypertension in 3 (3.1%). Anti-topoisomerase I antibody (anti-Scl70) positivity was present in 15 patients (15.5%) and anti-centromere antibody (ACA) positivity in 63 (64.9%). Nine patients (9.3%) were smokers and 6 (6.2%) reported an alcohol consumption of 3 or more units/day. Median body mass index (BMI) was 25.4 Kg/m2[21.4, 29.1], with 5 patients (5.2%) being underweight. Vitamin D insufficiency was reported in 19 patients (19.6%). Twenty-one patients (21.6%) have been exposed to oral glucocorticoids (GCT) for more than 3 months at a dose of 5mg daily or more. Eleven patients (11.3%) had previous low impact fractures: 10 of which were vertebral and 1 wrist fracture. Regarding the prescribed anti-osteoporotic treatment (AOP), we found: alendronate (n=7, 7.2%), zoledronic acid (n=7, 7.2%), denosumab (n=2, 2.1%) and teriparatide (n=1, 1%).Low BMD was present in 45 patients (46.4%); median femoral neck BMD (FN-BMD) was 0.827 [0.709, 0.893].Ten year probability of fracture (%) was: median risk for major fracture was 5.1 [3.5, 9.7] and 3.8 [2.5, 8], with and without FN-BMD, respectively; for hip fracture the estimated risk was 1.2 [0.6, 3.1] and 1.0 [0.4, 2.5], with and without FN-BMD, respectively. According to FRAX thresholds for the Portuguese population, 25 patients (25.8%) met criteria to start AOP treatment. Among them, only 10 patients (40%) started it, as the agreement between the indication to treat by FRAX and the onset of treatment was weak (k= 0.338). A strong agreement was found between FRAX risk threshold with DXA and World Health Organization (WHO) threshold for starting AOP (k= 0.814) and no agreement was found between FRAX risk without DXA and WHO threshold.FN-BMD presented a weak correlation with BMI (r = 0.393), a moderate inverse correlation with major fracture risk with and without FN-BMD (r = -0.704, r=-0.412, respectively) and with hip fracture risk with and without FN-BMD (r = -0.799, r=-0.412, respectively). Major fracture risk with and without FN-BMD presented a moderate correlation with spine fractures (r = 0.350; r=0.397, respectively).No correlation was found between WHO threshold and spine fractures. No correlations were found between FN-BMD or fracture risk estimated by FRAX and disease manifestations, anti-Scl70 or ACA positivity, vitamin D insufficiency, smoking or GCT use.Conclusion:In our cohort, low BMD was prevalent and had correlation with BMI. FRAX appears to be an useful instrument as it correlated with spine fractures, contrary to what was verified when we used the WHO threshold. Early monitoring of BMD and estimating fracture risk using FRAX appear to be useful tools for the prevention of fractures in this population.Disclosure of Interests:Salomé Garcia: None declared, Bruno Miguel Fernandes: None declared, Sara Ganhão: None declared, Maria Rato: None declared, Filipe Pinheiro: None declared, Georgina Terroso: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Lúcia Costa: None declared

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SAT0296 SERUM LEPTIN LEVELS IN SYSTEMIC SCLEROSIS PATIENTS WITH ELECTROCARDIOGRAPHIC ABNORMALITIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3390 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1093.1-1093

Author(s):

G. Pellegrino ◽

K. Stefanantoni ◽

F. Facioni ◽

C. Angelelli ◽

A. Gigante ◽

...

Keyword(s):

Systemic Sclerosis ◽

Chronic Diseases ◽

Cardiac Fibrosis ◽

Serum Levels ◽

High Serum ◽

Control Group ◽

Pathologic Finding ◽

Serum Leptin ◽

Ecg Abnormalities

Background:Electrocardiographic (ECG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) cases and they are associated with other systemic manifestations as well as with a worse prognosis. There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic and therapeutic approaches to patients with ECG abnormalities, due to their actual low sensitivity and specificity. Adipokines are circulating proteins that appear dysregulated in SSc and leptin in particular is synthesized in response to inflammatory conditions and seems to play a proinflammatory and pro-fibrotic action in SSc. Interesting, many studies in the last years have underlined its role in the cardiac remodeling mechanisms and in the development of cardiac fibrosis in other chronic diseases.Objectives:Aim of our study is to evaluate the role of leptin in the development of cardiac rhythm disorders (CRD) during SSc. Furthermore, by the analysis of the clinical and demographical parameters of our SSc patients, we tried to define other possible features associated with increased serum leptin concentration.Methods:We included eighty-five SSc patients, fulfilling the 2013 ACR/EULAR classification criteria, attending the Regional Rare Disease Center of Policlinico Umberto I of Rome. Fifty presented significant CRD at non-invasive diagnostic techniques (12 Lead ECG, 24-hour Holter ECG). Demographic, clinical, conventional cardiovascular risk factors were examined; instrumental and laboratory assessments were obtained, together with ECG recordings. Thirty-five SSc patients without pathologic finding at ECG traces, matched for demographic and clinical features, were recruited as the control group. In all cases, after obtaining written informed consent, blood samples were taken to measure serum levels of leptin using an ELISA assay (Life Technologies-Italia).Results:The fifty SSc patients with CRD (mean age 51±15 years; F:M 41:9) had pulmonary fibrosis (PF) in 32 cases (64%) and a BMI >25Kg/m2in 22 (44%) while in the control group of thirty-five SSc patients (mean age 49±16 years; F:M 33:2) PF was found in 15 (43%) and a BMI >25Kg/m2in 9 (35%); We detected significantly higher median values of serum leptin in SSc patients with CRD compared to the control group (12027 pg/ml IQR 12314 versus 6392 pg/ml IQR 7103;p 0,0009). Additionally, SSc patients with a BMI> 25 kg/m2(31 cases) as well as those with PF (47 cases) showed a significantly higher median serum leptin levels compared to those with BMI <25 kg/m2(13161 pg/ml IQR 13610 versus 8187 pg/ml IQR 8255;p 0,0008) and those without PF (11740 pg/ml IQR 11940 versus 7616 pg/ml IQR 7855;p 0,0079).Conclusion:To our knowledge this is the first report on high serum levels of leptin in SSc patients with CRD that also confirms its increase in those cases with a BMI >25 kg/m2and with PF, according to scientific literature data. The role of leptin in the pathogenesis of SSc remains unclear although it is already known its involvement in the development of cardiac fibrosis during other chronic diseases. On the basis of these results we speculate on leptin involvement in the pathogenesis of CRD during SSc, although further studies are needed with larger cohort of patients.References:[1]Vacca A et al. Rheumatology, 2014[2]Tyndall AJ et al. Ann Rheum Dis, 2010[3]Muresan L et al. Iran J Pub Health, 2017[4]Sanna T et al. Indian Pacing Electrophysiol J, 2009[5]Riccieri V et al. Clin Exp Rheumatol, 2011[6]Żółkiewicz J et al. Arch Dermatol Res, 2019[7]Huby AC et al. Circulation, 2015[8]Shulze PC et al. Clin Chim Acta, 2005[9]Van de Hoogen F et al. Arthritis Rheum, 2013[10]Gui X et al. Biochem Biophys Res Commun, 2018Disclosure of Interests:Greta Pellegrino: None declared, Katia Stefanantoni Consultant of: ItalfarmacoBoehringer Ingelheim, Fausta Facioni: None declared, Carlotta Angelelli: None declared, Antonietta Gigante: None declared, Roberto Badagliacca: None declared, Carmine Dario Vizza: None declared, Sergio Morelli: None declared, Edoardo Rosato: None declared, Valeria Riccieri: None declared

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