Search

PsoP27 is an antigen expressed in psoriatic lesions. It plays an inflammatory role in psoriasis. This study objective was to characterize antibodies (Abs) against PsoP27 in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Levels of Abs against native and citrullinated PsoP27 in PsA and RA patients' synovial fluid (SF) and sera were determined by ELISA. SF of osteoarthritis (OA) patients and sera of healthy donors were used as controls. Levels of Abs against PsoP27 were correlated with disease activity scores. Abs against native and citrullinated PsoP27 levels in SF of PsA (n = 48; 0.38 ± 0.03 and 0.44 ± 0.04, respectively) and RA (n = 22; 0.57 ± 0.1 and 0.62 ± 0.09, respectively) were significantly higher than in OA patients (n = 23; 0.14 ± 0.01 and 0.15 ± 0.01, respectively) (p <.0001). For both Abs, there were no significant differences between their level in PsA and RA patients. There was no difference in the level of Abs against citrullinated PsoP27 in SF of seronegative versus seropositive RA patients. Levels of Abs against both native and citrullinated PsoP27 in the SF and level of systemic C-reactive protein in PsA correlated positively, while in RA there were no significant correlations with disease activity scores. No differences in level of Abs against PsoP27 were found in the sera of all three study groups. Abs against native and citrullinated PsoP27 are present in PsA and RA SF but not in those of OA patients, suggesting a potential role of those Abs in inflammatory joint diseases. [ABSTRACT FROM AUTHOR]

Objectives To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. Methods Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. Results A total of 158 PsA patients [mean (s. d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (β = 0.18, P  = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (β = 0.06, P  = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P   <  0.05). Associations between enthesitis and synovitis were also demonstrated on the level of the elbow, knee and ankle joints (P   <  0.05). In addition, sonographic enthesitis was significantly associated with older age, male sex, swollen joint count, CRP level and physical occupation. Conclusions Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4, anti-programmed cell death 1, and anti-programmed cell death ligand 1 (PD-L1) antibodies, are currently widely used in oncology clinical practice, achieving considerable success in improving disease outcomes. New checkpoint targets are being discovered and investigated through basic science research and clinical trials. ICI remove negative regulatory immune signals on T cells, leading to immune activation and induction of antitumor immunity. Patients who receive ICI, however, are at risk for developing immune-related adverse events (irAEs), which are attributed to increased T cell activity against antigens in both tumors and in healthy tissues, to increased inflammatory cytokine levels, to increased levels of preexisting autoantibodies, and to enhanced complement-mediated inflammation. Arthritis is one of the most common irAEs. ICI-induced rheumatic irAEs are categorized by levels of severity which guide the choice of treatment options. Management of ICI-induced rheumatic irAEs includes the use of glucocorticoids, disease-modifying antirheumatic drugs (mainly methotrexate), and biological agents (e.g., tumor necrosis factor, interleukin-6 receptor, and CD20 inhibitors). This review aims to summarize the current ICI subtypes, their role in rheumatic irAEs development, and therapies currently used in clinical practice to manage irAEs. In addition, we propose to use an ex vivo personalized diagnostic assay for the selection of the most effective ICI with antirheumatic drugs combinations that will inhibit the advancement of ICI-induced adverse events. [ABSTRACT FROM AUTHOR]

Monocytes are innate immune cells that play a dual role in protection of host against pathogens and initiation and perpetuation of inflammatory disorders including joint diseases. During inflammation, monocytes migrate from peripheral blood to tissues via chemokine receptors where they produce inflammatory factors. Monocytes are classified into three subsets, namely: classical, intermediate and non-classical, each subset has particular function. Synovium of patients with inflammatory joint diseases, such as rheumatoid arthritis and psoriatic arthritis as well as osteoarthritis, is enriched by monocytes that differ from circulatory ones by distinct subsets distribution. Several therapeutic agents used systemically or locally through intra-articular injections in arthritis management modulate monocyte subsets. This scoping review summarized the existing literature delineating the effect of common therapeutic agents used in arthritis management on circulating and synovial monocytes/macrophages. As certain agents have an inhibitory effect on monocytes, we propose to test their potential to inhibit synovial monocytes via an ex-vivo platform based on cultured synovial fluid mononuclear cells derived from patients with rheumatic diseases. Information obtained from the ex-vivo platform can be applied to explore the therapeutic potential of medications in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives To report the discrepancies and agreements between US, MRI and radiography of the hand in PsA, and to compare the sensitivity and specificity of US and radiography to MRI as the gold standard imaging study in PsA. Methods All of the 100 prospectively recruited consecutive PsA patients underwent clinical assessment and concomitant radiographic, US and MRI studies of the MCP, PIP and DIP joints of one hand. Synovitis, flexor tenosynovitis, extensor paratenonitis, erosions and bone proliferations were identified and scored. All readers were blinded to clinical data, and agreement was calculated based on prevalence-adjusted bias-adjusted kappa (PABAK). Results The prevalence of synovitis, flexor tenosynovitis, extensor paratenonitis and erosions was similar for US and MRI, while that of bone proliferation was significantly increased in US and radiography compared with MRI (P   <  0.001). The absolute agreement between US and MRI was good-to-very good for synovitis (85–96%, PABAK = 0.70–0.92), flexor tenosynovitis (93–98%, PABAK = 0.87–0.96) and extensor paratenonitis (95–98%, PABAK = 0.90–0.97). Agreement between US, MRI and radiography was 96–98% (PABAK = 0.92–0.97) for erosions and 71–93% (PABAK = 0.47–0.87) for bone proliferations. Sensitivity of US with MRI as gold standard was higher for synovitis (0.5–0.86) and extensor paratenonitis (0.63–0.85) than for flexor tenosynovitis (0.1–0.75), while the specificity was high for each pathology (0.89–0.98). Conclusion There is very good agreement between US and MRI for the detection of inflammatory changes in finger joints in PsA. US, radiography and MRI have a good-to-very good agreement for destructive changes. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with T cell dysregulation. The lymphocyte‐activation gene (LAG)‐3 is one of the regulatory receptors expressed on T cells in a soluble form. LAG‐3 expression on T cells was analyzed in vitro in PsA patients with minimal disease activity (MDA), active disease (non‐MDA) and healthy controls. In cultured in‐vitro peripheral blood mononuclear cells (PBMCs), LAG‐3 expression on CD4+ T cells was similar in both MDA PsA patients (7.5 ± 0.9) (n = 14) and healthy controls (7.8 ± 0.6) (n = 15), but significantly lower in non‐MDA PsA patients (3.1 ± 0.3) (n = 13) (p < 0.0001). An inverse correlation between PsA clinical disease activity and %CD4+LAG‐3+ T cells in vitro was observed (composite psoriatic disease activity index r = −0.47, p < 0.02 and psoriatic arthritis disease activity score, r = −0.51, p < 0.008). In‐vitro co‐culture of CD4+ T cells with anti‐tumor necrosis factor (TNF) or anti‐interleukin (IL)‐17A had no effect on LAG‐3+ expression in MDA PsA patients and healthy controls. In non‐MDA patients, anti‐TNF, but not anti‐IL‐17A, restored the %CD4+LAG‐3+ T cells (7.9 ± 0.9 and 3.2 ± 0.4, respectively) (p < 0.0004). Lower soluble LAG‐3 levels were found in sera of naive to biological PsA patients (n = 39) compared to healthy controls (n = 35) (p < 0.03). Impaired LAG‐3 on CD4+ T cells may reflect active PsA disease state. Anti‐TNFs have potency to up‐regulate the CD4+LAG‐3+ T cells in vitro. [ABSTRACT FROM AUTHOR]