Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide variability of clinical manifestations due to the potential involvement of several tissues and internal organs, with a relapsing and remitting course. Dysregulation of innate and adaptive immune systems, due to genetic, hormonal and environmental factors, may be responsible for a broad spectrum of clinical manifestations, affecting quality of life, morbidity and mortality. Bone involvement represents one of the most common cause of morbidity and disability in SLE. Particularly, an increased incidence of osteoporosis, avascular necrosis of bone and osteomyelitis has been observed in SLE patients compared to the general population. Moreover, due to the improvement in diagnosis and therapy, the survival of SLE patient has improved, increasing long-term morbidities, including osteoporosis and related fractures. This review aims to highlight bone manifestations in SLE patients, deepening underlying etiopathogenetic mechanisms, diagnostic tools and available treatment.
A review of the available literature was performed in order to summarize the existing evidence between osteoblast dysfunction and clinical features in non-hereditary sclerosing bone diseases. It has been known that proliferation and migration of osteoblasts are concerted by soluble factors such as fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), bone morphogenetic protein (BMP) but also by signal transduction cascades such as Wnt signaling pathway. Protein kinases play also a leading role in triggering the activation of osteoblasts in this group of diseases. Post-zygotic changes in mitogen-activated protein kinase (MAPK) have been shown to be associated with sporadic cases of Melorheostosis. Serum levels of FGF and PDGF have been shown to be increased in myelofibrosis, although studies focusing on Sphingosine-1-phosphate receptor was shown to be strongly expressed in Paget disease of the bone, which may partially explain the osteoblastic hyperactivity during this condition. Pathophysiological mechanisms of osteoblasts in osteoblastic metastases have been studied much more thoroughly than in rare sclerosing syndromes: striking cellular mechanisms such as osteomimicry or complex intercellular signaling alterations have been described. Further research is needed to describe pathological mechanisms by which rare sclerosing non hereditary diseases lead to osteoblast dysfunction.
Calcium Pyrophosphate Crystal Deposition (CPPD) disease is characterized by the deposition of calcium pyrophosphate crystals in the cartilage. In most cases, it can manifest as a subclinical condition named chondrocalcinosis, often revealed by joint x-ray examination. In other cases, deposition can cause flares of arthritis, known as acute CPP crystal arthritis. In the last few years, many pathogenic pathways have been discovered. Interleukin-1 (IL-1) plays a key role in the pathogenesis of CPPD disease, both as a mediator of inflammatory response to crystals and as a promoter of damage to articular cartilage. In this review, we investigated the role of IL-1R inhibitor, such as Anakinra, as an alternative to the various therapeutic strategies for CPPD disease, especially among patients resistant to traditional treatment with NSAIDs, corticosteroids and colchicine.
Objectives: IL-17 modulates the synthesis of several molecules involved in the pathogenesis of Systemic Sclerosis (SSc). Vitamin D (1,25(OH)2D3) shows anti-fibrotic properties and it is able to affect the IL-17 production in several experimental conditions. The aim of this study is to assess the production of IL-17A and pro-fibrotic cytokines in peripheral blood mononuclear cells (PBMCs) from subjects with SSc in basal conditions and after treatment with 1,25(OH)2D3 and IL-17A neutralizing antibodies. Methods:The production of IL-17A and pro-fibrotic cytokines (TGFβ, CTGF and FGF2) in PBMCs obtained from 51 SSc patients and 31 healthy subjects was assessed both in basal conditions and in presence of anti-IL17A antibodies and several concentrations of 1,25(OH)2D3. The association of cytokines production with clinical disease characteristics and the in vitro effect of 1,25(OH)2D3 and IL-17A inhibition were assessed.Results: PBMCs from SSc subjects produced higher amount IL-17A, TGFβ, CTGF and FGF2 compared t o healthy controls. IL17, TGFβ, CTGF and FGF2 levels were higher in SSc patients with interstitial lung disease and digital ulcers, whereas IL-17A production was lower in patients with PAH. IL-17A inhibition reduced the production of FGF2, whereas enhanced the synthesis of TGFβ and CTGF. 1,25(OH)2D3 decreased the production of IL17A and pro-fibrotic cytokines in a dose-dependent manner. Conclusions: IL-17A is involved in the regulation of fibrogenesis in SSc, and could represent an intriguing potential therapeutic target, even if its role remains controversial. 1,25(OH)2D3 inhibits both IL-17A and pro-fibrotic cytokines, confirming its potential anti-fibrotic effect.
Objectives Survival and death prognostic factors of systemic sclerosis (SSc) patients varied during the last decades. We aimed to update the 5- and 10-year survival rates and identify prognostic factors in a multicentre cohort of Italian SSc patients diagnosed after 2009. Methods Patients who received a diagnosis of SSc after January 1st, 2009, and were longitudinally followed up in 4 Italian Rheumatologic Centres were retrospectively assessed up to December 31st, 2020. Overall survival of SSc patients was described using the Kaplan-Meier method. Predictors of mortality at 10-year follow-up were assessed by the Cox-regression model. A comparison of our cohort with the Italian general population was performed by determining the standardized mortality ratio (SMR). Results A total of 912 patients (91.6% females, 20% dcSSc) were included. Overall survival rates at 5 and 10 years were 94.4%, and 89.4% respectively. The SMR was 0.96 (95% CI 0.81–1.13), like that expected in the Italian general population. Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) associated with pulmonary hypertension (PH) significantly reduced survival (p< 0.0001). Main death predictors were male gender (HR = 2.76), diffuse cutaneous involvement (HR = 3.14), older age at diagnosis (HR = 1.08), PAH (HR = 3.21), ILD-associated PH (HR = 4.11), comorbidities (HR = 3.53), and glucocorticoid treatment (HR = 2.02). Conclusions In the last decade, SSc patients have reached similar mortality of that expected in the Italian general population. Male gender, diffuse cutaneous involvement, comorbidities, and PAH with or without ILD represent the main poor prognostic factors.
Background:Previous study evidenced a cross-reactivity between Sars-Cov-2 antibodies and autoimmune tissue antigen involved in connective tissue diseases, as nuclear antigen (NA), extractable nuclear antigen (ENA), histone and collagen (1). No study has been published about the titer of Sars-Cov-2 antibodies in non-infected patients with autoimmune disease.Objectives:To evaluate the titer of SARS-CoV-2 antibodies in non-COVID-19 patients and compare it between systemic sclerosis (SSc) patients and healthy controls (HC).Methods:A total of 58 patients with SSc (who fulfilled ACR/EULAR 2013 SSc classification criteria) and 18 HC were enrolled. Sera of all participants were collected, and SARS-CoV-2 antibodies (IgG and IgM) were evaluated by means ELISA. In all participants swabs for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction assay were reported negative. Demographic, clinical, and autoimmune serological characteristics of SSc patients were recorded. The normal distribution was assessed using the Shapiro–Wilk’s test. Exclusion criteria was previous or actual Sars-Cov-2 infection. Comparisons between study groups of patients were evaluated by the Student’s t-test or Mann – Whitney U-test as appropriate. The differences between categorial variables were assessed by Pearson chi-square or Fisher’s exact test, as opportune. Statistical significance was set at p ≤ 0.05.Results:We observed significant differences between SSc patients and HC in serum levels of Sars-Cov-2 antibodies (IgG: 1,4±2,1 AU/ml vs 0,36±0,19 AU/ml respectively (p=0,001); and IgM: 2,5±3,1 AU/ml vs 0,8±0,7 AU/ml (p=0,022)). In 5 SSc patients was found titer of Sars-Cov-2 antibodies (IgG) exceeding the cut-off, but the control of swabs for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction assay were negative. No significative differences in Sars-Cov-2 autoantibodies titer were found in subgroup of SSc patients with or without ILD or PAH, limited or diffuse skin subset, and different autoantibodies profile. Furthermore, antibodies titer was not associated with different drugs (steroid, methotrexate, mofetil-mycophenolate and bosentan) in use.Conclusion:A cross mimicking between Sars-Cov-2 antibodies and antinuclear antibodies or anti ENA could be hypothesized. Further studies are necessary to unravel the reliability of Sars-Cov-2 antibodies detection in autoimmune disease.References:[1]Vojdani, A., Vojdani, E., & Kharrazian, D. (2021). Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: Implications for autoimmune diseases. Frontiers in Immunology, 11, 3679Disclosure of Interests:None declared
Background:Systemic sclerosis (SSc) is one of the connective tissue diseases with the poorer prognosis and disease-related causes, particularly pulmonary fibrosis, PAH and cardiac involvement, accounting the most deaths.Objectives:This multicentre study aimed to evaluate the global survival and any predictor of mortality in a large multicentric cohort of SSc patients.Methods:We performed a retrospective analysis examining the medical records of our longitudinal SSc cohorts with a median (IQR) follow-up of 11 (6-18) years from 3 Scleroderma Units since January 2009. All clinical, laboratory and instrumental findings have been recorded and analyzed using Chi-squared tests, Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models.Results:Data from 750 SSc patients (91.9% female; mean (SD) age at first Non-Raynaud symptom 48.4 (15.3) years, median (IQR) disease duration 3 (0-8) years; diffuse cutaneous involvement 162 (21.6%) patients) fulfilling the 1980 ARA and/or 2013 ACR/EULAR classification criteria, were collected. All patients were positive for ANA, anti-Topo-I Abs were found in 235 (31.3%) and Cenp-B Abs in 300 (40%) patients. 98 (13.1%) patients were positive to other Abs (Anti-RNA polymerase III, anti-Pm/Scl) and anti-ENA were negative/unknown for 117 (15.6%) patients. Interstitial lung disease (ILD) was present in 202 (26.9%), pulmonary arterial hypertension (PAH) was found in 29 (3.9%), and 50/750 (6.7%) patients presented pulmonary hypertension combined with ILD (PH-ILD). The overall 10-years survival was 93.1% and, it was significantly impaired by the presence of ILD, PAH or PH-ILD [Figure]. The univariate analysis showed that female gender, higher age at first Non-Raynaud symptom, earlier referral to a tertiary Scleroderma center, absence of any ENA antibodies, and PH-ILD presence were survival predictors. After multivariate analysis the significance of PH-ILD was lost [Table]. Disease duration, basal Rodnan skin score, smoking, renal or gastrointestinal comorbidities, NYHA functional class, steroid or immune-suppressive treatments did not reach the statistically significance.Conclusion:Our study demonstrated a global 10-years survival rate over 93%. Male patients and rapid evolution of Non-Raynaud symptoms represent the main death predictors in our SSc cohort. A rapid referral to a tertiary rheumatological centre and early treatment with effective agents are associated to a better prognosis.Figure.Kaplan-Meier curves for 5-years survival in SSc patients (Log-rank 8.96, p=0.03).Table.Prognostic factors for 10-years survival at univariate and multivariate analysis.UNIVARIATE ANALYSISMULTIVARIATE ANALYSISHR95%ICPHR95%ICPFemale gender0.350.15-0.810.010.310.15-0.660.002Age at first Non-Raynaud symptom1.071.04-1.10.0011.081.05-1.110.001Time referral to a tertiary SSc centre0.830.76-0.920.0010.840.77-0.930.001Absence of any ENA antibodies0.080.01-0.620.010.090.01-0.710.02PH-ILD presence2.61.01-6.820.042.40.93-6.10.069Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Enrico De Lorenzis: None declared, Addolorata Corrado: None declared, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Marco Fornaro: None declared, Fabio Montini: None declared, Livio Urso: None declared, Lucrezia Verardi: None declared, Alberto Altomare: None declared, Francesco Paolo Cantatore: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD
: HCV is a global health problem affecting mainly the liver and often characterized by extrahepatic manifestions mediated by autoimmune reactions. Among these, arthritis and arthralgia are most frequent, as well as the presence of cryoglobulinemia that may induce vasculitis, and sicca syndrome. Thus, HCV appears to be a trigger for autoimmune response as demonstrated by the finding of autoantibody in a high percentage of serum of these patients. Therefore, it is important that clinicians recognize these autoimmune manifestations as symptoms due to an autoimmune activity triggered by HCV, in order to give the correct diagnosis and start an effective therapy strategy. Therefore, clinical examination, searching of markers of infection as well as autoantibody patterns should be performed to make a correct differential diagnosis. The treatment should be based on antiviral drugs associated to immunosuppressive drugs according to autoimmune manifestations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.