B cell phenotype and intracellular signaling in patients with systemic sclerosis

The objective of the study was to explore the phenotype and intracellular signaling events of B cells in patients with systemic sclerosis (SSc). Peripheral blood B cell surface markers CD19 and CD22 were evaluated by flow cytometry in 23 patients with SSc and seven healthy individuals. Levels of intracellular kinases Lyn, Syk and P-Y 348 Syk along with phosphatase SHP-1 were examined with Western immunoblotting in selected patients. P-Y 822 CD22 was subsequently evaluated flow cytometrically in antigen receptor stimulated B cells. A statistically significant decrease in CD22 B cell surface expression was found in the diffuse subset of patients (median CD22 MFI ± SD was 5.90 ± 2.35 vs 10.20 ± 1.88 for patients vs healthy controls respectively; p=0.021), while no statistically significant change was found regarding CD19. CD22 under-expression was more pronounced when interstitial lung disease (ILD) was present (median CD22 MFI ± SD was 5.90 ± 2.25 vs 10.20 ± 1.88 for patients with ILD vs healthy controls respectively; p=0.011). CD22 phosphorylation following B cell receptor (BCR) stimulation was also found to be impaired in patients with diffuse SSc (median change in MFI ± SD was 0.28 ± 0.09 vs 0.38 ± 0.08 for patients vs healthy controls respectively; p=0.034). Low CD22 expression was arithmetically correlated with kinase Lyn under-expression (Pearson coefficient 0.926; p=ns) in B cells from a small sample of patients. These results suggest that CD22 under-expression and impaired phosphorylation along with implications for Lyn kinase aberrations could contribute to the activated B cell phenotype in SSc.Ο σκοπός της εργασίας ήταν η μελέτη του φαινοτύπου και της ενδοκυττάριας σηματοδότησης των Β λεμφοκυττάρων σε ασθενείς με συστηματική σκληροδερμία (ΣΣ). Οι επιφανειακοί δείκτες CD19 και CD22 εξετάστηκαν με κυτταρομετρία ροής σε περιφερικό αίμα 23 ασθενών με ΣΣ και 7 υγιών εθελοντών. Μελετήθηκαν επίσης τα επίπεδα των ενδοκυττάριων κινασών Lyn, Syk και P-Y 348 Syk και της φωσφατάσης SHP-1 με μέθοδο ανοσοαποτυπώματος κατά Western σε επιλεγμένους ασθενείς. Σε μεταγενέστερο χρόνο ελέγχθηκε η φωσφορυλίωση του CD22 στη θέση τυροσίνης 822 με κυτταρομετρία ροής σε Β λεμφοκύτταρα μετά από διέγερση του Β κυτταρικού υποδοχέα (BCR). Στατιστικά σημαντική ελάττωση διαπιστώθηκε στην επιφανειακή έκφραση του CD22 στους ασθενείς με διάχυτη ΣΣ (διάμεση τιμή του CD22 MFI ± SD ήταν 5.90 ± 2.35 έναντι 10.20 ± 1.88 για τους ασθενείς έναντι των υγιών αντίστοιχα, p=0.021), ενώ δεν παρατηρήθηκε στατιστικά σημαντική διαφορά ως προς το CD19. Η ελαττωμένη έκφραση του CD22 ήταν εντονότερη όταν συνυπήρχε διάμεση πνευμονοπάθεια (διάμεση τιμή του CD22 MFI ± SD ήταν 5.90 ± 2.25 έναντι 10.20 ± 1.88 για τους ασθενείς με διάμεση πνευμονοπάθεια έναντι των υγιών αντίστοιχα, p=0.011). Η φωσφορυλίωση του CD22 μετά από διέγερση του BCR διαπιστώθηκε ότι είναι επίσης ελαττωμένη στη διάχυτη νόσο (διάμεση τιμή διαφοράς του MFI ± SD ήταν 0.28 ± 0.09 έναντι 0.38 ± 0.08 για τους ασθενείς έναντι των υγιών αντίστοιχα, p=0.034). Η ελαττωμένη επιφανειακή έκφραση του CD22 συσχετίσθηκε αριθμητικά με υποέκφραση της κινάσης Lyn (Pearson coefficient 0.926, p=ns) σε Β λεμφοκύτταρα από ένα μικρό αριθμό ασθενών. Η ελαττωμένη επιφανειακή έκφραση και φωσφορυλίωση του CD22 μαζί με πιθανή διαταραχή στην έκφραση της κινάσης Lyn μπορεί να συνεισφέρουν στον ενεργοποιημένο φαινότυπο του Β λεμφοκυττάρου στη ΣΣ

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. Their clinical efficacy is well-documented, but the side effects associated with their use are still under investigation. These drugs cause several immune-related adverse events (ir-AEs), some of which stand within the field of rheumatology. Herein, we present a literature review performed in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICIs. The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis. Non-musculoskeletal rheumatic manifestations are less frequent, with the most prominent being sicca, vasculitides and sarcoidosis. Cases of systemic lupus erythematosus or scleroderma are extremely rare. The majority of musculoskeletal ir-AEs are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation. In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed. Oncologists should periodically screen patients receiving ICIs for new-onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms

Cardiovascular Disease in the Systemic Vasculitides

The vasculitides are a heterogeneous group of disorders, characterized by inflammatory cell infiltration and necrosis of blood vessels that cause vascular obstruction or aneurysm formation, affecting various organs such as lungs, kidneys, skin and joints. Cardiac involvement is commonly encountered in primary systemic vasculitis and it is associated with increased morbidity and mortality. Depending on the dominant pathophysiological mechanism, heart complications may manifest in different ways, including myocardial ischemia due to impaired micro- or macrovascular circulation, progressive heart failure following valvular heart disease and myocardial dysfunction, (sub) clinical myocarditis, pericarditis, pulmonary hypertension as well as arteritis of coronary vessels. Beyond cardioprotective regimens, aggressive immunosuppression reduces the inflammatory burden and modulates the progression of cardiovascular complications. Perioperative management of inflammation, when surgical treatment is indicated, improves surgical success rates and postoperative long-term prognosis. We aim to provide an overview of the pathogenetic, diagnostic and therapeutic principles of cardiovascular involvement disease in the various forms of systemic vasculitis

Multicenter Cross-sectional Study of Patients with Rheumatoid Arthritis in Greece: Results from a cohort of 2.491 patients.

AIM OF THE STUDY: To evaluate the current disease characteristics, treatment and comorbidities of rheumatoid arthritis (RA) in Greece. METHODS: Multicenter, cross-sectional study with a 9-month recruitment period between 2015 and 2016. Demographics, disease characteristics, treatment and comorbidities were collected via a web-based platform. RESULTS: 2.491 RA patients were recruited: 96% from tertiary referral centers, 79% were females with a mean age of 63.1 years and disease duration of 9.9 years. Fifty-two percent were rheumatoid factor and/or anti-CCP positive, while 41% had erosive disease. Regarding treatment, 82% were on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), 42% on biologic DMARDs (TNFi: 22%, non-TNFi: 20%) and 40% on corticosteroids (mean daily dose: 5.2 mg). Despite therapy, 36% of patients had moderate and 12% high disease activity. The most frequent comorbidities were hypertension (42%), hyperlipidemia (33%), osteoporosis (29%), diabetes mellitus (15%) and depression (12%). Latent tuberculosis infection (positive tuberculin skin test or interferon gamma release assay) was diagnosed in 13 and 15.3% of patients, respectively. Regarding chronic viral infections, 6.2% had history of herpes zoster while 2% and 0.7% had chronic hepatitis B and C virus infection, respectively. A history of serious infection was documented in 9.6%. Only 36% and 52% of the participants had ever been vaccinated against pneumococcus and influenza virus, respectively. CONCLUSION: This is one of the largest epidemiologic studies providing valuable data regarding the current RA characteristics in Greece. Half of patients were seropositive but despite therapy, half displayed residual disease activity, while preventive vaccination was limited

Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases

Objective tau o report outcomes of breakthrough COVID-19 in comparison with COVID-19 in unvaccinated patients with systemic rheumatic diseases (SRDs). Methods Patients with SRD with COVID-19 (vaccinated and unvaccinated) were included by their rheumatologists in a registry operated by the Greek Rheumatology Society in a voluntarily basis. Type, date and doses of SARS-CoV-2 vaccines were recorded, and demographics, type of SRD, concurrent treatment, comorbidities and COVID-19 outcomes (hospitalisation, need for oxygen supplementation and death) were compared between vaccinated and unvaccinated patients. Results Between 1 March 2020 and 31 August 2021, 195 patients with SRD with COVID-19 were included; 147 unvaccinated and 48 vaccinated with at least one dose of a SARS-CoV-2 vaccine (Pfizer n=38 or AstraZeneca n=10). Among vaccinated patients, 29 developed breakthrough COVID-19 >14 days after the second vaccine dose (fully vaccinated), while 19 between the first and <14 days after the second vaccine dose (partially vaccinated). Despite no differences in demographics, SRD type, treatment or comorbidities between unvaccinated and vaccinated patients, hospitalisation and mortality rates were higher in unvaccinated (29.3% and 4.1%, respectively) compared with partially vaccinated (21% and 0%) or fully vaccinated (10.3% and 0%) patients. Conclusions Vaccinated patients with SRD with breakthrough COVID-19 have better outcomes compared with unvaccinated counterparts with similar disease/treatment characteristics