Non-Pharmacological Interventions for Treating Psoriatic Arthritis.

Background and Objective: In this review, we discuss evidence concerning the management of psoriatic arthritis (PsA) patients with non-pharmacological interventions and additionally develop physical training protocols that could be prescribed to these patients. Methods: We selected 110 articles, published on PubMed and Google Scholar databases from 1972 to date, investigating the effects of generic hygienic-dietary recommendations and training programs in PsA or psoriasis (PSO) individuals. Results: Although data in support are limited, aerobic, endurance, and strength exercises as well as complementary techniques may all be useful in preserving or improving residual functional capacity, joint flexibility, and muscle strength. Exercise may reduce systemic inflammation, pain, and fatigue and additionally control PsA comorbidities, like dysmetabolism or obesity. Conclusions: The polyhedral clinical expression of PsA underlines the need for a multidisciplinary approach combining the synergistic effects of pharmacological and non-pharmacological treatments. The latter range from preventive measures, like dietary modifications, weight loss, and cigarette smoking cessation, to personalized training protocols according to disease activity and phenotype, comorbidities, and individual tolerability. In these patients, we strongly encourage the regular practice of motor activity at progressively increasing intensity with combined supervised aerobic, strength, endurance, and stretching exercises.

Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis.

BACKGROUND: After the start of the worldwide COVID-19 vaccination campaign, there were increased reports of autoimmune diseases occurring de novo after vaccination. This in silico analysis aimed to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most widely administered COVID-19 vaccines, which could induce autoimmunity in predisposed individuals. METHODS: The FASTA sequence of the protein encoded by the BNT-162b2 vaccine served as the key input to the Immune Epitope Database and Analysis Resource. Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC-ligand assays without MHC restriction were searched and analyzed. HLA disease associations were screened on the HLA-SPREAD platform by selecting only positive markers. RESULTS: By 7 May 2023, a total of 5693 epitopes corresponding to 21 viral but also human proteins were found. The latter included CHL1, ENTPD1, MEAF6, SLC35G2, and ZFHX2. Importantly, some autoepitopes may be presented by HLA alleles positively associated with various immunological diseases. CONCLUSIONS: The protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals through a molecular mimicry mechanism. Genotyping for HLA alleles may help identify individuals at risk. However, further wet-lab studies are needed to confirm this hypothesis.

COVID-19 mRNA vaccines as hypothetical epigenetic players: Results from an in silico analysis, considerations and perspectives.

OBJECTIVES: To investigate in silico the occurrence of epigenetic crosstalk by nucleotide sequence complementarity between the BNT162b2 mRNA vaccine and whole human genome, including coding and noncoding (nc)RNA genes. To correlate these results with those obtained with the original spike (S) gene of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). METHODS: The publicly available FASTA sequence of the BNT162b2 mRNA vaccine and the SARS-CoV-2 isolate Wuhan-Hu-1 S gene (NC_045512.2) were used separately as key input to the Ensembl.org library to evaluate base pair match to human GRCh38 genome. Human coding and noncoding genes harboring hits were assessed for functional activity and health effects using bioinformatics tools and GWAS databases. RESULTS: The BLAT analysis against the human GRCh38 genome revealed a total of 37 hits for BNT162b2 mRNA and no hits for the SARS-CoV-2 S gene. More specifically, BNT162b2 mRNA matched 19 human genes whose protein products are variously involved in enzyme reactions, nucleotide or cation binding, signaling, and carrier functions. In BLASTN analysis of ncRNA genes, BNT162b2 mRNA and SARS-CoV-2 S gene matched 17 and 24 different human genomic regions, respectively. Overall, characterization of the matched noncoding sequences revealed stronger interference with epigenetic pathways for BNT162b2 mRNA compared with the original S gene. CONCLUSION: This pivotal in silico analysis shows that SARS-CoV-2 S gene and the BNT162b2 mRNA vaccine exhibit Watson-Crick nucleotide complementarity with human coding or noncoding genes. Although they do not share the same complementarity pattern, both may disrupt epigenetic mechanisms in target cells, potentially leading to long-term complications.

Management of Patients Affected by Giant Cell Arteritis during the COVID-19 Pandemic: Telemedicine Protocol TELEMACOV.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries, prevalently affecting elderly people. Both early diagnosis and regular monitoring are necessary for the correct management of GCA. Following the outbreak of the COVID-19 pandemic, government decisions aiming at reducing the contagion led to reductions in health activities, limiting them to urgent cases. At the same time, remote monitoring activities have been implemented through telephone contacts or video calls carried out by specialists. In line with these deep changes affecting the worldwide healthcare system and in consideration of the high risk of GCA morbidity, we activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by GCA during the COVID-19 pandemic) in order to remotely monitor patients affected by GCA. The aim of this study was to evaluate the effectiveness of telemedicine in the follow-up of patients already diagnosed with GCA. This was a monocenter observational study. Patients with a previous diagnosis of GCA admitted to the Rheumatology Unit of the University Hospital "Città della Salute e della Scienza" in Turin were monitored every 6-7 weeks by means of video/phone calls from 9 March to 9 June 2020. All patients were asked questions concerning the onset of new symptoms or their recurrence, exams carried out, changes in current therapy, and satisfaction with video/phone calls. We performed 74 remote monitoring visits in 37 GCA patients. Patients were mostly women (77.8%) and had a mean age of 71.85 ± 9.25 years old. The mean disease duration was 5.3 ± 2.3 months. A total of 19 patients received oral glucocorticoids (GC) alone at the time of diagnosis with a daily dose of 0.8-1 mg/kg (52.7 ± 18.3 mg) of prednisone, while 18 patients were treated with a combination of oral steroids (at the time of diagnosis, the prednisone mean dose was 51.7 ± 18.8 mg) and subcutaneous injections of tocilizumab (TCZ). During the follow-up, patients additionally treated with TCZ reduced their GC dose more than patients treated with GC alone (p = 0.03). Only one patient, who was treated with GC alone, had a cranial flare and needed to increase the dosage of GC, which led to rapid improvement. Furthermore, all patients proved very adherent to the therapies (assessed by Medication Adherence Rating Scale (MARS)) and considered this type of monitoring very satisfactory according to a Likert scale (mean score 4.4 ± 0.2 on a 1-5 range). Our study shows that telemedicine can be safely and effectively used in patients with GCA under control as a possible alternative, at least for a limited period of time, to traditional visits.

Interaction between Long Noncoding RNAs and Syncytin-1/Syncytin-2 Genes and Transcripts: How Noncoding RNAs May Affect Pregnancy in Patients with Systemic Lupus Erythematosus.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) often suffer from obstetric complications not necessarily associated with the antiphospholipid syndrome. These events may potentially result from the reduced placental synthesis of the fusogenic proteins syncytin-1 and syncytin-2, observed in women with pregnancy-related disorders. SLE patients have an aberrant noncoding (nc)RNA signature that may in turn dysregulate the expression of syncytin-1 and syncytin-2 during placentation. The aim of this research is to computationally evaluate and characterize the interaction between syncytin-1 and syncytin-2 genes and human ncRNAs and to discuss the potential implications for SLE pregnancy adverse outcomes. METHODS: The FASTA sequences of the syncytin-1 and syncytin-2 genes were used as inputs to the Ensembl.org library to find any alignments with human ncRNA genes and their transcripts, which were characterized for their tissue expression, regulatory activity on adjacent genes, biological pathways, and potential association with human disease. RESULTS: BLASTN analysis revealed a total of 100 hits with human long ncRNAs (lncRNAs) for the syncytin-1 and syncytin-2 genes, with median alignment scores of 151 and 66.7, respectively. Only lncRNAs TP53TG1, TTTY14, and ENSG00000273328 were reported to be expressed in placental tissue. Dysregulated expression of lncRNAs TP53TG1, LINC01239, and LINC01320 found in this analysis has previously been described in SLE patients as well as in women with a high-risk pregnancy. In addition, some of the genes adjacent to lncRNAs aligned with syncytin-1 or syncytin-2 in a regulatory region might increase the risk of pregnancy complications or SLE. CONCLUSIONS: This is the first computational study showing alignments between syncytin-1 and syncytin-2 genes and human lncRNAs. Whether this mechanism affects syncytiotrophoblast morphogenesis in SLE females is unknown and requires further investigation.

Impaired VEGF-A-Mediated Neurovascular Crosstalk Induced by SARS-CoV-2 Spike Protein: A Potential Hypothesis Explaining Long COVID-19 Symptoms and COVID-19 Vaccine Side Effects?

Long coronavirus disease-19 (COVID-19) is a newly discovered syndrome characterized by multiple organ manifestations that persist for weeks to months, following the recovery from acute disease. Occasionally, neurological and cardiovascular side effects mimicking long COVID-19 have been reported in recipients of COVID-19 vaccines. Hypothetically, the clinical similarity could be due to a shared pathogenic role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike (S) protein produced by the virus or used for immunization. The S protein can bind to neuropilin (NRP)-1, which normally functions as a coreceptor for the vascular endothelial growth factor (VEGF)-A. By antagonizing the docking of VEGF-A to NRP-1, the S protein could disrupt physiological pathways involved in angiogenesis and nociception. One consequence could be the increase in unbound forms of VEGF-A that could bind to other receptors. SARS-CoV-2-infected individuals may exhibit increased plasma levels of VEGF-A during both acute illness and convalescence, which could be responsible for diffuse microvascular and neurological damage. A few studies suggest that serum VEGF-A may also be a potential biomarker for long COVID-19, whereas evidence for COVID-19 vaccines is lacking and merits further investigation.

Lipid rafts as viral entry routes and immune platforms: A double-edged sword in SARS-CoV-2 infection?

Lipid rafts are nanoscopic compartments of cell membranes that serve a variety of biological functions. They play a crucial role in viral infections, as enveloped viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exploit rafts to enter or quit target cells. On the other hand, lipid rafts contribute to the formation of immune synapses and their proper functioning is a prerequisite for adequate immune response and viral clearance. In this narrative review we dissect the panorama focusing on this singular aspect of cell biology in the context of SARS-CoV-2 infection and therapy. A lipid raft-mediated mechanism can be hypothesized for many drugs recommended or considered for the treatment of SARS-CoV-2 infection, such as glucocorticoids, antimalarials, immunosuppressants and antiviral agents. Furthermore, the additional use of lipid-lowering agents, like statins, may affect the lipid composition of membrane rafts and thus influence the processes occurring in these compartments. The combination of drugs acting on lipid rafts may be successful in the treatment of more severe forms of the disease and should be reserved for further investigation.

Sequence complementarity between human noncoding RNAs and SARS-CoV-2 genes: What are the implications for human health?

OBJECTIVES: To investigate in silico the presence of nucleotide sequence complementarity between the RNA genome of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and human non-coding (nc)RNA genes. METHODS: The FASTA sequence (NC_045512.2) of each of the 11 SARS-CoV-2 isolate Wuhan-Hu-1 genes was retrieved from NCBI.nlm.nih.gov/gene and the Ensembl.org library interrogated for any base-pair match with human ncRNA genes. SARS-CoV-2 gene-matched human ncRNAs were screened for functional activity using bioinformatic analysis. Finally, associations between identified ncRNAs and human diseases were searched in GWAS databases. RESULTS: A total of 252 matches were found between the nucleotide sequence of SARS-CoV-2 genes and human ncRNAs. With the exception of two small nuclear RNAs, all of them were long non-coding (lnc)RNAs expressed mainly in testis and central nervous system under physiological conditions. The percentage of alignment ranged from 91.30% to 100% with a mean nucleotide alignment length of 17.5 ± 2.4. Thirty-three (13.09%) of them contained predicted R-loop forming sequences, but none of these intersected the complementary sequences of SARS-CoV-2. However, in 31 cases matches fell on ncRNA regulatory sites, whose adjacent coding genes are mostly involved in cancer, immunological and neurological pathways. Similarly, several polymorphic variants of detected non-coding genes have been associated with neuropsychiatric and proliferative disorders. CONCLUSION: This pivotal in silico study shows that SARS-CoV-2 genes have Watson-Crick nucleotide complementarity to human ncRNA sequences, potentially disrupting ncRNA epigenetic control of target genes. It remains to be elucidated whether this could result in the development of human disease in the long term.

Physical activity in idiopathic inflammatory myopathies: two intervention proposals based on literature review.

Idiopathic inflammatory myopathies (IIM) are rare diseases affecting skeletal muscles and leading to progressive muscle weakness and disability. Thanks to the better understanding of their pathogenesis, the management of IIM has been noteworthily implemented in recent years. Current therapeutic strategies include pharmacological and non-pharmacological interventions, among which physical exercise represents a useful option, able to ameliorate disease activity without worsening muscle inflammation. The aim of this narrative review is therefore to provide an updated overview of the benefits of physical exercise in patients with IIM and to suggest plausible training programs to be applied in patients with dermatomyositis, polymyositis, necrotizing myopathy, and inclusion body myositis. In this regard, a combined strategy mixing aerobic and resistance exercises could positively affect the pro-inflammatory and metabolic pathways occurring in skeletal muscles, while promoting muscle fiber regeneration and repair.

Efficacy and Safety of Biosimilar and Originator Etanercept in Rheumatoid Arthritis Patients: Real-Life Data.

BACKGROUND: There is a lack of real-life clinical data for biosimilar etanercept, an anti-TNF blocking fusion protein. We describe the comparable efficacy and safety of originator and biosimilar etanercept in rheumatoid arthritis (RA) patients in a real-life clinical setting. Our data confirm that a biosimilar etanercept can be safely used as first-line treatment as well as in patients switched from a previous originator compound. OBJECTIVES: To compare the efficacy and safety of originator and biosimilar etanercept in a cohort of RA patients attending two Italian hospitals. METHODS: The study involved 81 consecutive adult RA patients treated for at least 6 months with originator or biosimilar etanercept and considered their clinical and laboratory data, concomitant medications, and adverse events at baseline, and after 3 and 6 months of treatment. RESULTS: Group 1 included 51 patients taking originator etanercept; group 2 included 30 taking biosimilar etanercept, including 19 who had been switched from the reference product. Despite a significant baseline difference in clinical disease activity, one-way analysis of variance showed that the two groups were clinically comparable after 6 months of treatment, and the same was true when only those receiving etanercept as first-line biological treatment were considered. Nine patients discontinued the treatment due to inefficacy or adverse events, which were never serious and were only reported in group 1. CONCLUSIONS: The efficacy and safety profiles of originator and biosimilar etanercept are comparable in RA patients in a real-life clinical setting. Further studies are needed to confirm these preliminary findings.

Antiphospholipid antibodies and risk of post-COVID-19 vaccination thrombophilia: The straw that breaks the camel's back?

Antiphospholipid antibodies (aPLs), present in 1-5 % of healthy individuals, are associated with the risk of antiphospholipid syndrome (APS), which is the most common form of acquired thrombophilia. APLs may appear following infections or vaccinations and have been reported in patients with COronaVIrus Disease-2019 (COVID-19). However, their association with COVID-19 vaccination is unclear. Notably, a few cases of thrombocytopenia and thrombotic events resembling APS have been reported to develop in recipients of either adenoviral vector- or mRNA-based COVID-19 vaccines. The aim of this review is therefore to speculate on the plausible role of aPLs in the pathogenesis of these rare adverse events. Adenoviral vector-based vaccines can bind platelets and induce their destruction in the reticuloendothelial organs. Liposomal mRNA-based vaccines may instead favour activation of coagulation factors and confer a pro-thrombotic phenotype to endothelial cells and platelets. Furthermore, both formulations may trigger a type I interferon response associated with the generation of aPLs. In turn, aPLs may lead to aberrant activation of the immune response with participation of innate immune cells, cytokines and the complement cascade. NETosis, monocyte recruitment and cytokine release may further support endothelial dysfunction and promote platelet aggregation. These considerations suggest that aPLs may represent a risk factor for thrombotic events following COVID-19 vaccination, and deserve further investigations.

The rationale for targeting the JAK/STAT pathway in scleroderma-associated interstitial lung disease.

The etiopathogenesis of systemic sclerosis (SSc)-associated interstitial lung disease (ILD) is still debated and no therapeutic options have proved fully effective to date. The intracellular Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is highly conserved among either immune or nonimmune cells and involved in inflammation and fibrosis. Evidence from preclinical studies shows that the JAK/STAT signaling cascade has a crucial role in the differentiation of autoreactive cells as well as in the extracellular matrix remodeling that occurs in SSc. Therefore, it is likely that the use of oral small molecule JAK-inhibitors, especially if prescribed early, may prevent or slow the progression of SSc-associated ILD, but few clinical studies currently support this hypothesis.

Prevalence of hepatitis B virus infection and risk of reactivation in rheumatic population undergoing biological therapy.

OBJECTIVES: Hepatitis B (HBV) is a common comorbidity among rheumatic patients. The prevalence of HBV infection and the rate of reactivation remain unclear. The literature data suggested a higher risk in chronic than in past infection. Currently, the literature data are mostly focused on anti-TNF and rituximab. This retrospective observational study aimed to analyse the prevalence of HBV infection and the risk of viral reactivation in a population of rheumatic patients undergoing anti-TNF and non-anti-TNF agents. METHODS: We analysed 1216 rheumatic patients, treated with both csDMARDs and bDMARDs between 2006 and 2017. Serologic markers for HBV (HBsAg, anti-HBs, anti-HBc) were performed prior and during biologic treatment. Patients with chronic or resolved infection were monitored every 3 months. RESULTS: The prevalence of HBV in our cohort was 15.7% (chronic infection: 0.4%, resolved infection: 12.6%, anti-HBc positivity alone: 2.6%). 12 (6.2%) out of 191 HBV infected patients experienced a reactivation. All of them showed markers of past infection. One patient experienced HBV reactivation despite lamivudine. Only one patient experienced acute hepatitis, probably due to the interruption of immunosuppressors in anticipation of surgery, not preceded by any HBV prophylactic treatment. CONCLUSIONS: HBV reactivation is a rare event in patients treated with a bDMARD and it can also occur while taking lamivudine, not only in chronic carriers (as per the literature data) but also in inactive ones. Regular screening followed by prompt treatment can prevent symptoms or complications. Due to the risk of hepatitis following the immune reconstitution, an antiviral therapy should be considered in the case of sudden discontinuation of csDMARDs or bDMARD.

Calcium physiology, metabolism and supplementation: a glance at patients with ankylosing spondylitis.

The aim of this review is to describe the metabolism of calcium in ankylosing spondylitis compared to physiologic conditions, and to present the current evidence on the benefits and disadvantages of calcium supplementation in these patients. A narrative review of the literature was conducted using the PubMed database and a total of 65 articles were selected. Calcium is involved in many physiopathological processes, including inflammation, bone loss and bone formation, all of which occur in ankylosing spondylitis. Many ankylosing spondylitis patients suffer from concomitant osteopenia or osteoporosis, which represent indications for calcium supplementation. Conversely, there are still concerns about the use of calcium salts for the prevention of bone fragility in non-osteoporotic or non-osteopenic patients. In these cases, biologic agents may indirectly normalize calcium dysmetabolism by rebalancing the cytokine milieu, in turn associated with bone remodeling. Calcium supplements may be disadvantageous for entheseal calcifications, but so far there are no clear data confirming that such an association exists.

Autoimmunity as the comet tail of COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can give rise to different clinical manifestations that are directly related to viral tissue damage or indirectly induced by the antiviral immune response. Hyper-activation of the immune system in an attempt to eradicate the infection may trigger autoimmunity. Several immune-mediated disorders have been described in SARS-CoV-2-infected individuals. These include cutaneous rashes and vasculitis, autoimmune cytopenia, anti-phospholipid syndrome, central or peripheral neuropathy, myositis and myocarditis. On the other hand, rheumatic patients were reported to have similar coronavirus disease 2019 (COVID-19) incidence, morbidity and mortality rates compared to general population. This opinion review will summarize the crucial immunologic steps which occur during SARS-CoV-2-infection that may link autoimmunity to COVID-19 and provides an opportunity for further discussion regarding this association.

JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Outlook on the Future.

Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. JAKi are characterized by a novel mechanism of action, consisting of the intracellular interruption of the JAK-STAT pathway crucially involved in the immune response. The aim of this narrative review is to globally report the most relevant pharmacological features and clinical outcomes of the developed and incoming JAKi for RA, based on the available preclinical and clinical evidence. A total of 219 papers, including narrative and systematic reviews, randomized controlled trials (RCTs), observational studies, case reports, guidelines, and drug factsheets, were selected. The efficacy and safety profile of both the first generation JAKi (baricitinib and tofacitinib) and the second generation JAKi (upadacitinib, filgotinib, peficitinib, decernotinib and itacitinib) were compared and discussed. Results from RCTs and real-life data are encouraging and outline a rapid onset of the pharmacologic effects, which are maintained during the time. Their efficacy and safety profile are comparable or superior to those of biologic agents and JAKi proved to be efficacious when given as monotherapy. Finally, the manufacturing of JAKi is relatively easier and cheaper than that of biologics, thus increasing the number of compounds being formulated and tested for clinical use.

Therapeutic peptides for the treatment of systemic lupus erythematosus: a place in therapy.

INTRODUCTION: Studies in vitro and in vivo have identified several peptides that are potentially useful in treating systemic lupus erythematosus (SLE). The rationale for their use lies in the cost-effective production, high potency, target selectivity, low toxicity, and a peculiar mechanism of action that is mainly based on the induction of immune tolerance. Three therapeutic peptides have entered clinical development, but they have yielded disappointing results. However, some subsets of patients, such as those with the positivity of anti-dsDNA antibodies, appear more likely to respond to these medications. AREAS COVERED: This review evaluates the potential use of therapeutic peptides for SLE and gives an opinion on how they may offer advantages for SLE treatment. EXPERT OPINION: Given their acceptable safety profile, therapeutic peptides could be added to agents traditionally used to treat SLE and this may offer a synergistic and drug-sparing effect, especially in selected patient populations. Moreover, they could temporarily be utilized to manage SLE flares, or be administered as a vaccine in subjects at risk. Efforts to ameliorate bioavailability, increase the half-life and prevent immunogenicity are ongoing. The formulation of hybrid compounds, like peptibodies or peptidomimetic small molecules, is expected to yield renewed treatments with a better pharmacologic profile and increased efficacy.

Systemic sclerosis Progression INvestiGation (SPRING) Italian registry: demographic and clinico-serological features of the scleroderma spectrum.

OBJECTIVES: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation). METHODS: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc. RESULTS: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features. CONCLUSIONS: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.

Retroviruses in the pathogenesis of systemic lupus erythematosus: Are they potential therapeutic targets?

The pathogenesis of systemic lupus erythematosus (SLE) is characterised by the hyper-activation of immunologic pathways related to the antiviral response. Exogenous and endogenous retroviruses, by integrating their DNA templates in the host cell genome, may epigenetically control the transcription of genes involved in the immune response. Furthermore, their nucleic acids or neo-synthesized proteins could stimulate the sensor molecules placed upstream the inflammatory cascade. Exogenous retroviruses, like human immunodeficiency virus, have been associated to SLE-like manifestations or to a fair SLE diagnosis. In addition, there is some evidence confirming a pathogenic role of human endogenous retroviruses in SLE. In line with these data, the use of antiretroviral agents could represent an attractive opportunity in the future therapeutic algorithms of this disease, but studies are still missing.