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Prominent Inflammatory Features of Monocytes/Macrophages in Acute Calcium Pyrophosphate Crystal Arthritis: a Comparison with Acute Gouty Arthritis.

ABSTRACT: Calcium pyrophosphate (CPP) crystals can present as acute inflammatory arthritis which is known as an acute CPP crystal arthritis. Although monocytes/macrophages have been shown to play a role in the initiation of crystal-mediated inflammatory responses, differences in their phenotypes between acute CPP crystal arthritis and acute gouty arthritis have not yet been investigated. We examined the immunological characteristics of synovial monocytes/macrophages in patients with acute CPP crystal and acute gouty arthritis. CD14⁺CD3^-CD19^-CD56^- cell frequencies in synovial fluid mononuclear cells (SFMCs) were measured. Expression of pro- and anti-inflammatory cytokines and markers was determined. The SFMCs were dominated by a population of monocytes/macrophages in acute CPP crystal arthritis similar to that in acute gout. Synovial monocytes/macrophages showed the phenotypes of infiltrated monocytes as shown by expression of CD88, C-C chemokine receptor type 2, myeloid-related protein (MRP)8 and MRP14 but not proto-oncogene tyrosine-protein kinase MER. Comparatively, the CD14⁺ cells from patients with acute CPP crystal arthritis had similar high levels of IL-1? and TNF-? production but significantly lower expression of IL-10 and M2 marker (CD163). The monocytes/macrophages had the capacity to produce IL-8 in response to CPP crystals. Proinflammatory features were more dominant in monocytes/macrophages during acute CPP crystal arthritis than those during acute gouty arthritis.

SUBMITTER: Jeong JH

PROVIDER: S-EPMC6597439 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Prominent Inflammatory Features of Monocytes/Macrophages in Acute Calcium Pyrophosphate Crystal Arthritis: a Comparison with Acute Gouty Arthritis.

Jeong Ji Hye JH Jung Jae Hyung JH Lee Jung Sun JS Oh Ji Seon JS Kim Yong-Gil YG Lee Chang-Keun CK Yoo Bin B Hong Seokchan S

Immune network 20190327 3

Calcium pyrophosphate (CPP) crystals can present as acute inflammatory arthritis which is known as an acute CPP crystal arthritis. Although monocytes/macrophages have been shown to play a role in the initiation of crystal-mediated inflammatory responses, differences in their phenotypes between acute CPP crystal arthritis and acute gouty arthritis have not yet been investigated. We examined the immunological characteristics of synovial monocytes/macrophages in patients with acute CPP crystal and ...[more]

PMID: 31281718

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Project description:ObjectivesCalcium pyrophosphate deposition (CPPD) disease, broadly defined, has been associated with increased risk of cardiovascular (CV) events. We investigated risk of CV events in patients with acute CPP crystal arthritis, the acute manifestation of CPPD.MethodsCohort study using Mass General Brigham electronic health record (EHR) data, 1991-2017. Patients with acute CPP crystal arthritis were identified using a published machine learning algorithm with positive predictive value 81%. Comparators were matched on year of EHR entry and index date of patients with acute CPP crystal arthritis (first positive synovial fluid CPP result or mention of 'pseudogout', or matched encounter). Major adverse cardiovascular event (MACE) was a composite of non-fatal CV event (myocardial infarction, acute coronary syndrome, coronary revascularisation, stroke) and death. We estimated incidence rates (IRs) and adjusted hazard ratios for MACE, non-fatal CV event and death, allowing for differential estimates during years 0-2 and 2-10. Sensitivity analyses included: (1) patients with acute CPP crystal arthritis diagnosed during outpatient visits, (2) patients with linked Medicare data, 2007-2016 and (3)patients matched on number of CV risk factors.ResultsWe matched 1200 acute CPP crystal arthritis patients to 3810 comparators. IR for MACE in years 0-2 was 91/1000 person-years (p-y) in acute CPP crystal arthritis and 59/1000 p-y in comparators. In years 2-10, IR for MACE was 58/1000 p-y in acute CPP crystal arthritis and 53/1000 p-y in comparators. Acute CPP crystal arthritis was significantly associated with increased risk for MACE in years 0-2 (HR 1.32, 95% CI 1.01 to 1.73) and non-fatal CV event in years 0-2 (HR 1.92, 95% CI 1.12 to 3.28) and years 2-10 (HR 2.18, 95% CI 1.27 to 3.75), but not death. Results of sensitivity analyses were similar to the primary analysis; in the outpatient-only analysis, risk of non-fatal CVE was significantly elevated in years 2-10 but not in years 0-2.ConclusionsAcute CPP crystal arthritis was significantly associated with elevated short and long-term risk for non-fatal CV event.

Project description:Background: Acute gouty arthritis (AGA) is the most common first symptom of gout, and the development of gout as a metabolic and immune inflammatory disease is also correlated with the gut microbiota. However, the mechanism of the effect of changes in the gut microbiota on AGA remains unclear. The intestinal flora can not only affect purine metabolism or regulate inflammation, but also influence the therapeutic effect of drugs on AGA. The aim of this study was to investigate the exact mechanism of modified Baihu decoction (MBD) in the treatment of AGA and whether it is related to the regulation of the structure of the intestinal flora. Methods: On the 21st day of MBD administration by continuous gavage, a rat acute gouty arthritis model was constructed using sodium urate (0.1 mL/rat, 50 mg/mL), and the ankle joint swelling was measured before and 4 h, 8 h, 24 h, and 48 h after the injection of sodium urate. After 48 h of sodium urate injection, serum, liver, kidney, ankle synovial tissue and feces were collected from rats. The collected samples were examined and analyzed using H&E, Elisa, Immunohistochemistry, Histopathology, 16S rDNA, and Biochemical analysis. To investigate the mechanism of MBD to alleviate AGA using pro-inflammatory factors and intestinal flora. Results: MBD (5.84, 35 g/kg) was administered orally to AGA rats and diclofenac sodium tablets (DS-tablets) were used as standard treatment control. Serum biochemical assessment confirmed that MBD is a safe drug for the treatment of AGA. In addition, our findings confirmed that MBD relieved AGA-related symptoms, such as toe swelling. Lowering serum levels of uric acid, IL-1β, and TGF-β1 immunohistochemical results also confirmed that MBD reduced the expression of inflammatory elements such as IL-1β, NLRP3, ASC, and Caspase-1 in synovial tissue.Furthermore, compared with control group, the 16s rDNA sequencing of AGA rat faeces revealed an increase in the relative abundance of Lachnospiraceae, Muribaculaceae, and Bifidobacteriaceae species. While the relative abundance of Lactobacillaceae, Erysipelotrichaceae, Ruminococcaceae, Prevotellaceae and Enterobacteriaceae showed a relative decrease in species abundance. Of these, the reduction in species abundance of Enterobacteriaceae was associated with a reduction in amino acid metabolism and environmental perception. After MBD therapeutic intervention, the disturbance of the intestinal flora caused by AGA was restored. Conclusion: In summary, MBD is an effective agent for the treatment of AGA, with the potential mechanism being the regulation of intestinal flora to control inflammation. This would help to promote the therapeutic effect of MBD on AGA.

Dataset Information

Prominent Inflammatory Features of Monocytes/Macrophages in Acute Calcium Pyrophosphate Crystal Arthritis: a Comparison with Acute Gouty Arthritis.

Publications

Prominent Inflammatory Features of Monocytes/Macrophages in Acute Calcium Pyrophosphate Crystal Arthritis: a Comparison with Acute Gouty Arthritis.

Similar Datasets

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