CD8 T cell-derived perforin regulates macrophage-mediated inflammation in a murine model of gout.

OBJECTIVES: Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. METHODS: We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. RESULTS: In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24 h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. CONCLUSIONS: Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.

Clinical joints manifestations in patients with psoriatic arthritis on musculoskeletal ultrasound.

OBJECTIVE: To investigate the clinical joints manifestations under musculoskeletal ultrasound (MSUS) and hematological findings in patients with psoriatic arthritis (PsA), which may provide a basis for improving the early diagnosis of PsA. METHODS: From September 2016 to February 2021, 328 patients with psoriasis visited the dermatological and rheumatic outpatient of the Beijing Friendship Hospital were enrolled in this retrospective study. Patients were enrolled according to a paired-design method. The PsA group included 164 patients diagnosed with PsA, and the control group included 164 patients diagnosed with psoriasis without PsA. Both groups of patients were evaluated by a rheumatoid immunologist, a dermatologist, and a sonographer. Demographic data, course of disease, severity of skin lesions, combined diseases, and previous treatment were all collected. All patients received MSUS and blood examinations. Lower extremity enthsis diseases were evaluated by Glasgow ultrasound enthesitis scoring system (GUESS). RESULTS: In the comparison of baseline clinical characteristics, the PsA group has longer course of psoriasis (P = 0.005), longer course of joints pain (P = 0.035), higher incidence of peripheral joints pain (P = 0.001), higher GUESS score (P < 0.001), and higher incidence of involved nails or toenails (P = 0.036) The most common joints involved were proximal interphalangeal joint (33.5%), knee (27.4%), and metacarpophalangeal joint (25.0%). Differences in clinical manifestations at different lower limb enthesitis on MSUS have also been proved. The positive incidences of rheumatoid factor (RF) (P = 0.002) and anti-cyclic citrullinated peptide (CCP) antibody (P < 0.001) in the PsA group were significantly higher than those in the control group. Binary Logistic regression showed that patients with anti-CCP antibody positive had a higher risk of active PsA compared to patients with negative antibodies in PsA group (OR: 0.626, 95%CI: 0.361-0.792, P < 0.05). CONCLUSION: In conclusion, the most common joints involved were proximal interphalangeal joint, knee, and metacarpophalangeal joint in patients with PsA, and the common types of diseased joints manifestations on MSUS were synovial thickening, fluid accumulation, bone destruction, increased blood flow signals, and attachment site inflammation. GUESS scoring systems can be used to identify PsA in patients with psoriasis. Psoriasis patients with RF and anti-CCP antibody positive were more likely to develop PsA, and anti-CCP antibody positive was a risk factor for active PsA. KEY POINTS: • GUESS scoring systems can be used to identify PsA in patients with psoriasis. • Psoriasis patients with RF and anti-CCP antibody positive were more likely to develop PsA, and anti-CCP antibody positive was a risk factor for active PsA.

Serum-soluble TRAIL: a potential biomarker for disease activity in myositis patients.

OBJECTIVES: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM). In this study, we examined the level and origin of serum-soluble TRAIL (sTRAIL) in patients with PM and DM and analyzed its association with disease activity and clinical features. METHOD: 11 PM patients, 33 DM patients, and 20 healthy controls were enrolled in this study. Clinical features were recorded when admitted, and disease activity was evaluated by myositis disease activity assessment visual analogue scale (MYOACT). TRAIL expression in muscle tissues was detected by immunohistochemistry. Serum sTRAIL levels were measured by enzyme-linked immunosorbent assay. The expression of membrane TRAIL (mTRAIL) and its receptors, including DR4 and DR5, on circulating T cells was analyzed by flow cytometry. RESULTS: TRAIL was expressed in infiltrated inflammatory cells in muscle tissues from patients. The serum sTRAIL level was markedly increased in patients and was positively correlated with the disease activity. Serum sTRAIL was decreased after therapy in patients and was specifically higher in patients with dysphagia, but lower in patients with autoantibody Jo-1 positive. The frequency of mTRAIL and its receptors on circulating T cells from patients were significantly elevated than that from healthy controls. CONCLUSIONS: The serum sTRAIL could be a biomarker for evaluating the disease activity of PM and DM, and targeting the generation of TRAIL in T cells might be a potential approach in the treatment of PM and DM.

Diagnostic accuracy of salivary gland ultrasonography with different scoring systems in Sjögren's syndrome: a systematic review and meta-analysis.

Noninvasive objective salivary gland ultrasonography (SGU) had been widely used to evaluate major salivary gland involvement in primary Sjögren's syndrome (pSS) and treatment responses. However, the evaluation score, diagnostic sensitivity, and diagnostic specificity significantly varied among clinical studies. We conducted this meta-analysis to assess the diagnostic accuracy of different SGU scoring systems using the American-European Consensus Group criteria. Of the 1301 articles retrieved from six databases, 24 met the criteria for quality assessment and 14 for meta-analyses. The pooled sensitivities were 75% (0-4) with I2 = 92.0%, 84% (0-16) with I2 = 63.6%, and 75% (0-48) with I2 = 90.9%; the pooled specificities were 93% (0-4) with I2 = 71.5%, 88% (0-16) with I2 = 65.4%, and 95% (0-48) with I2 = 83.9%; the pooled diagnostic odds ratios were 71.26 (0-4) with I2 = 0%, 46.3 (0-16) with I2 = 73.8%, and 66.07 (0-48) I2 = 0%; the areas under the SROC curves were 0.95 (0-4), 0.93 (0-16), and 0.94 (0-48). These results indicated that the 0-4 scoring system has a higher specificity and a less heterogeneity than other systems, and could be used as a universal SGU diagnostic standard.