FRI0464 Clinical manifestations of persistent antiphospholipid antibodies in systemic sclerosis patients

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

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SAT0316 ANTI-PM/SCL ANTIBODIES IN SYSTEMIC SCLEROSIS: CLINICAL ASSOCIATIONS IN THE RESCLE COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3304 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1103.1-1104

Author(s):

N. Iniesta-Arandia ◽

G. Espinosa ◽

A. Guillen del Castillo ◽

C. Tolosa ◽

G. M. Lledó ◽

...

Keyword(s):

Systemic Sclerosis ◽

Survival Data ◽

Death Rate ◽

Administrative Support ◽

Medical Science ◽

Survival Rates ◽

Clinical Manifestations ◽

Study Group ◽

Allergy Immunol ◽

Science Service

Background:Anti-PM/Scl antibodies are associated to systemic sclerosis (SSc) but are not specific to SSc. The true prevalence of anti-PM/Scl antibodies in SSc is unknown, ranging from 2.5% to 12.5%. An association between anti-PM/Scl antibodies with muscular involvement, pulmonary fibrosis, calcinosis, and a relatively benign prognosis have been described.Objectives:To compare the clinical manifestations and prognosis of SSc patients according the presence of anti-PM/Scl antibodies in the cohort of RESCLE (Spanish Scleroderma Registry).Methods:From the Spanish Scleroderma Study Group database, we selected patients in whom anti-PM/Scl antibodies had been tested. We compared demographic features, clinical manifestations, laboratory characteristics, and survival data between patients according the anti-PM/Scl antibodies status.Results:72 out of 947 (7%) patients tested positive for anti-PM/Scl antibodies. As presenting SSc manifestations, patients with anti-PM/Scl antibodies had higher prevalence of puffy fingers (11% versus 2%; p=0.002) and arthralgias (11% versus 4%; p=0.03), and lower prevalence of Raynaud’s phenomenon (65% versus 82%, p=0.002). Regarding cumulative manifestations, myositis (51% versus 15%; p<0.001), arthritis (43% versus 22%; p=0.001), and interstitial lung disease (ILD) (60% versus 45%, p=0.014) were more prevalent in patients with anti-PM/Scl antibodies. In fact, those patients with anti-Pm/Scl antibodies presented with FVC (77.4% ± 23.1% versus 85.8% ± 23,1%; p=0.006) and more severe ILD defined as FVC <70% (41% versus 24%; p=0.004). Death rate was similar in patients with and without PM/Scl antibodies (18% versus 17%; p=0.871).We did not find differences in terms of death rate nor in the causes of death (SSc and non-SSc related) according to the anti-PM/Scl antibodies profile.The 5- and 10-years survival rates of patients with anti-PM/Scl antibodies were 91% and 82% respectively, without differences with those without these antibodies (93% and 85%, respectively).Conclusion:In Spanish SSc patients, the presence of anti-PM/Scl antibodies confer a distinctive clinical profile. However, anti-PM/Scl antibodies do not play a role in the prognosis of these patients.References:[1]Stochmal A, Czuwara J, Trojanowska M, Rudnicka L. Antinuclear antibodies in systemic sclerosis: an update. Clin Rev Allergy Immunol 2020;58(1):40-51. doi: 10.1007/s12016-018-8718-8.Acknowledgments:We gratefully acknowledge all investigators who are part of the RESCLE Registry. We also thank the RESCLE Registry Coordinating Centre, S&H Medical Science Service, for their quality control data, logistic and administrative support and Prof. Salvador Ortiz, Universidad Autónoma de Madrid and Statistical Advisor S&H Medical Science Service for the statistical analysis of the data presented in this paper.Disclosure of InterestsNerea Iniesta-Arandia: None declared, Gerard Espinosa Speakers bureau: Glaxo-Smith-Kline, Janssen, Boehringer, Rovi, Alfredo Guillen del Castillo: None declared, Carles Tolosa Consultant of: Actelion pharmaceuticals, GSK, MSD., Gema Maria Lledó: None declared, Dolores Colunga Argüelles Consultant of: Actelion pharmaceuticals, GSK, MSD., Cristina González-Echávarri: None declared, Luis Sáez-Comet: None declared, Norberto Ortego: None declared, Jose Antonio Vargas-Hitos: None declared, Manuel Rubio-Rivas: None declared, Mayka Freire: None declared, Juan José Rios: None declared, Monica Rodriguez-Carballeira: None declared, Luis Trapiella Martínez: None declared, Vicent Fonollosa Pla Speakers bureau: Actelion, Carmen Pilar Simeón-Aznar Consultant of: Actelion pharmaceuticals, GSK, MSD., on behalf of RESCLE Investigators, Autoimmune Diseases Study Group (GEAS): None declared

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Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations

Journal of Ophthalmic Inflammation and Infection ◽

10.1186/s12348-021-00240-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Gunay Uludag ◽

Neil Onghanseng ◽

Anh N. T. Tran ◽

Muhammad Hassan ◽

Muhammad Sohail Halim ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Clinical Manifestations ◽

Autoimmune Disorder ◽

Ocular Involvement ◽

Ocular Manifestations ◽

Different Types ◽

Thrombotic Complications ◽

Specific Factors ◽

Arteries And Veins

AbstractAntiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

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Childhood-Onset Systemic Lupus Erythematosus: Antiphospholipid Antibodies in 37 Patients and Their First-Degree Relatives

PEDIATRICS ◽

10.1542/peds.92.6.849 ◽

1993 ◽

Vol 92 (6) ◽

pp. 849-853

Author(s):

Charles Molta ◽

Olivier Meyer ◽

Christine Dosquet ◽

Marcela Montes de Oca ◽

Marie-Claude Babron ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Clinical Manifestations ◽

Fetal Loss ◽

Childhood Onset ◽

Systemic Lupus ◽

First Degree Relatives ◽

Antiphosphatidylethanolamine Antibodies ◽

Onset Systemic Lupus Erythematosus

Objective. Antiphospholipid antibodies (aPL) are noted with increased frequency in patients with systemic lupus erythematosus (SLE). The main manifestations found to be associated with aPL are arterial and venous thrombotic events, thrombocytopenia, and recurrent pregnancy loss This study is an attempt to define the incidence of aPL in patients with childhood-onset SLE and in their relatives and to correlate their presence with clinical manifestations, and especially, to evaluate the risk of thrombosis in aPL-positive subjects. Methodology. We studied 37 unrelated patients and 107 of their first-degree relatives. VDRL, IgG and IgM anticardiolipin, and IgG antiphosphatidylethanolamine antibodies were studied in all probands during periods of clinical remission and in first-degree relatives at the time of interview. Lupus anticoagulant had only been studied in probands during an SLE flare-up. Results. Thirty-eight percent of probands and 19% of relatives were positive for at least one aPL, with little over-lap between the different aPL studied. -No aPL-negative proband developed thrombosis. Two of the aPL-positive probands had thrombotic events before testing, and a third one showed thrombosis after testing. Only two probands had high levels of IgG aCL and showed thrombosis. The occurrence of aPL positivity in relatives was not always related to its presence in probands. None of the aPL-positive relatives had hadthrombosis, but recurrent fetal loss was noted in one aPL-positive mother with SLE. Although there was a high frequency of SLE, SLE-like disease, auto-immune disorders or positive serological findings for lupus in first-degree relatives, many of these relativew did not test positive for aPL. Conclusion. The high levels of IgG aCL may be considered a risk factor for thrombosis. Findings in relatives suggest a multifactorial origin for autoimmune disease and antibody production.

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The contribution of epigenetics to the pathogenesis and gender dimorphism of systemic sclerosis: a comprehensive overview

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x20918456 ◽

2020 ◽

Vol 12 ◽

pp. 1759720X2091845 ◽

Cited By ~ 1

Author(s):

Bianca Saveria Fioretto ◽

Irene Rosa ◽

Eloisa Romano ◽

Yukai Wang ◽

Serena Guiducci ◽

...

Keyword(s):

Systemic Sclerosis ◽

X Chromosome ◽

Clinical Manifestations ◽

Connective Tissue Disorder ◽

Epigenetic Modifications ◽

Unknown Etiology ◽

Comprehensive Overview ◽

Gender Dimorphism ◽

Immune Related Genes ◽

The Right

Systemic sclerosis (SSc) is a life-threatening connective tissue disorder of unknown etiology characterized by widespread vascular injury and dysfunction, impaired angiogenesis, immune dysregulation and progressive fibrosis of the skin and internal organs. Over the past few years, a new trend of investigations is increasingly reporting aberrant epigenetic modifications in genes related to the pathogenesis of SSc, suggesting that, besides genetics, epigenetics may play a pivotal role in disease development and clinical manifestations. Like many other autoimmune diseases, SSc presents a striking female predominance, and even if the reason for this gender imbalance has yet to be completely understood, it appears that the X chromosome, which contains many gender and immune-related genes, could play a role in such gender-biased prevalence. Besides a short summary of the genetic background of SSc, in this review we provide a comprehensive overview of the most recent insights into the epigenetic modifications which underlie the pathophysiology of SSc. A particular focus is given to genetic variations in genes located on the X chromosome as well as to the main X-linked epigenetic modifications that can influence SSc susceptibility and clinical phenotype. On the basis of the most recent advances, there is realistic hope that integrating epigenetic data with genomic, transcriptomic, proteomic and metabolomic analyses may provide in the future a better picture of their functional implications in SSc, paving the right way for a better understanding of disease pathogenesis and the development of innovative therapeutic approaches.

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Occlusive retinal vasculitis associated with systemic sclerosis and antiphospholipid antibodies

American Journal of Ophthalmology Case Reports ◽

10.1016/j.ajoc.2021.101206 ◽

2021 ◽

Vol 24 ◽

pp. 101206

Author(s):

Caleb C. Ng ◽

Sandip Suresh ◽

James T. Rosenbaum ◽

H. Richard McDonald ◽

Emmett T. Cunningham

Keyword(s):

Systemic Sclerosis ◽

Antiphospholipid Antibodies ◽

Retinal Vasculitis

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Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis

Diagnostics ◽

10.3390/diagnostics11112116 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2116

Author(s):

Marija Geroldinger-Simić ◽

Thomas Bögl ◽

Markus Himmelsbach ◽

Norbert Sepp ◽

Wolfgang Buchberger

Keyword(s):

Systemic Sclerosis ◽

High Performance ◽

Clinical Manifestations ◽

Plasma Phospholipid ◽

Phospholipid Metabolism ◽

Internal Organs ◽

New Biomarkers ◽

First Time

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

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