Remodeling Articular Immune Homeostasis with an Efferocytosis-inspired Nanoimitator Mitigates Rheumatoid Arthritis

Massive intra-articular infiltration of the pro-inflammatory macrophages is a prominent feature of rheumatoid arthritis (RA) lesions, which are thought to underlie articular immune dysfunction, severe synovitis and ultimate joint erosion. Here we report an efferocytosis-inspired nanoimitator (EINI) for in situ targeted reprogramming of the synovial inflammatory macrophages (SIMs) and thus thwarting their autoimmune attack and reinstating articular immune homeostasis, which mitigates RA. The EINI consisted of a drug-based core with an oxidative stress-responsive phosphatidylserine (PtdSer) corona and a shell of P-selectin-blocking motif, low molecular weight heparin (LMWH). When systemically administrated, the LMWH on the EINI first bound to P-selectin overexpressed on endothelium in subsynovial capillaries, which functioned as an antagonist disrupting neutrophils synovial trafficking. Due to the high dysregulation of the synovial microvasculature, the EINI subsequently enriched in joint synovium where the shell was exfoliated upon the reactive oxygen species stimulation, and PtdSer corona was then exposed. In an efferocytosis-like manner, the PtdSer-coroneted core was in turn phagocytosed by SIMs, which synergistically terminated the SIMs-initiated pathological cascades and serially reconstructed the intra-articular immune homeostasis, conferring a chondroprotection effect. These findings demonstrate that SIMs can be precisely remodeled via the efferocytosis-mimetic strategy, which holds great potential for RA treatment.

Automatic Detection of 3D Joint Erosion in Hand HR-pQCT: A Level Set-Based Approach

In this paper, we propose a 3D fully automatic joint erosion algorithms for hand HR-pQCT, and its performance can reach consensus with human specialist.

Automatic Detection of 3D Joint Erosion in Hand HR-pQCT: A Level Set-Based Approach

In this paper, we propose a 3D fully automatic joint erosion algorithms for hand HR-pQCT, and its performance can reach consensus with human specialist.

Automatic Detection of 3D Joint Erosion in Hand HR-pQCT: A Level Set-Based Approach

In this paper, we propose a 3D fully automatic joint erosion algorithms for hand HR-pQCT, and its performance can reach consensus with human specialist.

AB0134 RELATIONSHIP BETWEEN INFLAMMATORY RATIOS AND RADIOGRAPHIC JOINT DAMAGE IN RHEUMATOID ARTHRITIS

Background:The tight control strategy is recommended in rheumatoid arthritis to tailor treatment for patients. This strategy requires regular monitoring of both disease activity and structural damage. However, radiographic assessement cannot be performed frequently and the modified Sharp score is rarely evaluated in current practice. Besides, no biomarker was able to mirror structural damage (1).Objectives:Our study aimed to assess the relationship between the modified Sharp score and the inflammatory ratios (platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), fibrinogen to albumin ratio (FAR) and CRP to albumin ratio (CAR)).Methods:We performed a cross-sectional study including 53 patients with rheumatoid arthritis (RA). A cell blood count, fibrinogen and an albumin blood test were measured for each patient. Inflammatory ratios were also measured (PLR, NLR, LMR, FAR, and CAR). Modified Sharp score and its components (erosion score and joint space narrowing score) were evaluated using the radiograph of hand and foot.Patients with infectious or hematological diseases were excluded from the study.Statistical analysis was performed using SPSS (Statistical Package for Social Sciences).Results:Of the 53 patients, 39 were female (Sex Ratio: 2.8). The mean age was 53.9 ± 12.7 years. The mean disease duration was 10.1 ± 8.2 years.The average age of the onset of the disease was 43.8±13.5 years.The mean DAS 28-ESR score was 4.64 ± 1.23. Forty three patients had a score higher than 3.2 (patients with moderate or high disease activity).The mean values of PLR, NLR, LMR, FAR and CAR were 161.62 ± 86.59, 2.84 ± 2.39, 4.99 ± 3.23, 0.12 ± 0.06 and 1.15 ± 1.38.The mean scores of joint erosion and joint space narrowing were respectively 12.76 ± 15.05 and 33.57 ± 25.80. The mean modified Sharp score was 46.33 ± 37.74.There was a positive correlation between modified Sharp score and following ratios: PLR (r: 0.501; p <10-3), NLR (r: 0.302; p:0.031), FAR (r: 0.300; p:0.030), CAR (r:0.286; p:0.042).Moreover, a positive correlation between joint space narrowing score and these ratios was identified: PLR (r: 0.558; p <10-3), NLR (r: 0.428; p:0.002), FAR (r: 0.371; p:0.007), CAR (r:0.387; p:0.005).Joint erosion score correlated with PLR (r: 0.299; p:0.033).No correlation was found between LMR and radiographic score.Conclusion:Our study showed that the modified Sharp score correlated with PLR, NLR, FAR and CAR in patients with RA. This finding suggests that these ratios could be used as inexpensive and reliable markers to reflect radiographic joint damage.Longitudinal studies are necessary to confirm our results.References:[1]Syversen SW, Landewe R, Van Der Heijde D, Bathon JM, Boers M, Bykerk VP, et al. Testing of the OMERACT 8 draft validation criteria for a soluble biomarker reflecting structural damage in rheumatoid arthritis: a systematic literature search on 5 candidate biomarkers. J Rheumatol. 2009;36(8):1769-84.Disclosure of Interests:None declared

Investigation of clinical and laboratory manifestations of rheumatoid arthritis depending on the level of serum fetuin-A

Aim of the study. To study the association between the serum FA in patients with RA and separate clinical and laboratory manifestations of the disease. Material and methods. A total of 140 subjects were enrolled in the study. Among them, 110 were RA patients and 30 were conventionally healthy subjects. Th e level of serum FA was measured in both groups. All patients underwent complete clinical and laboratory examination and X-ray imaging of the impaired joints. Results. The level of normal FA in healthy subjects calculated as M±2σ totalled 653.55-972.19μg/ml. The mean level of FA in RA patients was 765.67±120.67μg/ ml, which is statistically lower than that in the donors: 812.95±76.21μg/ml (t=-2.03; p=0.0437). Th e mean FA level in conventionally healthy patients was statistically higher than the same index in RA-factor positive patients with cyclic citrullinated peptide antibodies, moderate and high activity, late clinical stage, X-ray stages III and IV, functional classes II, III and IV, joint erosion, abarticular manifestations and the presence of complicating diseases. Intra-group analysis (odds ratio and adjusted odd ratio) showed the patients with lower FA level (below 653.55μg/ml) to have a 14-fold higher possibility of CCP antibodies positivity (6-fold after adjustment), 1.86-fold higher disease activity (2.39-fold aft er adjustment), 6.6-fold higher probability of X-ray stage IV (with no statistical signifi cance after adjustment) and 29-fold higher chance of presence of complications (46-fold after adjustment). Conclusion. According to the data obtained in our study, lowering of the serum FA level is characteristic to RA patients. The hepatokine concentration below 653.55μg/ml may suggest 2.39-fold higher chance of higher disease activity and 46-fold higher probability of complicated RA progression.

Elevated serum granzyme B levels are associated with disease activity and joint damage in patients with rheumatoid arthritis

Objectives Little is known about the roles of granzyme B in rheumatoid arthritis (RA). We aimed to evaluate the serum level of granzyme B in patients with RA and determine relationships with clinical features and joint destruction of RA. Methods We enrolled 100 patients with RA, 50 patients with osteoarthritis (OA), and 50 healthy controls (HC). Granzyme B serum concentrations were measured by ELISA; we then analyzed associations between granzyme B levels, clinical features, and joint destruction by calculating Sharp scores and disease activity as measured by Disease Activity Score-28 based on erythrocyte sedimentation rate (DAS28-ESR) in patients with RA. Results Compared with HC and patients with OA, serum granzyme B levels in patients with RA were remarkably elevated. Serum granzyme B levels did not differ between patients with OA and HC. Granzyme B levels correlated with ESR, rheumatoid factor, swollen joint counts, joint erosion scores, total Sharp scores, and DAS28-ESR. Moreover, patients with RA with high disease activity had higher granzyme B levels. Conclusions Serum granzyme B levels were elevated significantly in patients with RA and correlated positively with disease activity and joint destruction. Serum granzyme B may have potential applications in laboratory evaluation of patients with RA.

AB0054 SYNOVIAL CD163+ MACROPHAGES ARE ASSOCIATED WITH RADIOGRAPHIC JOINT DESTRUCTION IN RHEUMATOID ARTHRITIS

Background:CD163, a hemoglobin scavenger receptor, has been identified as a marker of M2 macrophages, it can promote the release of IL-10 and carbon oxide. Researches on inflammatory diseases and tumors have suggested that CD163 plays anti-inflammatory effect and promotes tumor growth and metastasis. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic synovitis with inflammatory cells infiltration including considerable macrophages. However, little is known about the role of CD163+ macrophages in RA synovium.Objectives:To investigate the expression and clinical significance of synovial CD163+ macrophages in RA.Methods:Seventy-five RA patients were recruited and clinical data including disease activity, HAQ and Sharp/van der Heijde-modified Sharp score of bilateral hands and wrists were collected. Synovial tissues were obtained by needle biopsies or arthroscopy of knee joints. Eighteen osteoarthritis (OA) and seventeen orthopedic arthropathies (orth.A) patients were included as controls. All synovium were stained with H&E and immunohistochemically for CD163, CD3, CD20, CD38, CD68, and CD15. Histologic changes of synovitis in H&E stained sections were graded with Krenn’s synovitis score.Results:Positive CD163 expression were found in both lining synoviocytes and sublining inflammatory cells. Both densities of lining and sublining CD163+ macrophages in RA synovium were significantly higher than that in OA or Orth.A synovium (140.47±66.93 vs. 17.85±7.70 vs. 19.76±5.26 and 417.92±249.62 vs. 27.58±14.19 vs. 29.87±9.33, allP<0.001, Figure 1).According to Krenn’s synovitis score, there were 68% RA patients showing high synovitis (score>4). Both lining and sublining synovial CD163+ macrophages were significantly higher than those showing low synovitis (lining: 158.40±62.91 vs. 122.06±66.74, sublining: 462.96±62.91 vs. 371.65±271.54, bothP<0.05). Meanwhile, the densities of lining and sublining CD163+ macrophages were both positively correlated with Krenn’s synovitis score (r=0.238 and 0.343, bothP<0.05).For clinical relationship in RA, the density of sublining CD163+ macrophages was positively correlated with total Sharp score (mTSS) (r=0.399,P<0.001), joint space narrowing subscore (r=0.248,P=0.032) and joint erosion subscore (r=0.457,P<0.001). While the density of lining CD163+ macrophages was positively correlated with mTSS (r=0.319,P=0.005) and joint erosion subscore (r=0.358,P=0.002). Meanwhile, the densities of sublining and lining CD68+ macrophages were also positively correlated with mTSS (r=0.253 and 0.242, bothP<0.05), of which the correlation was weaker than that of CD163+ macrophages (Figure 2). There were no significant correlation between the density of CD163+ macrophages and disease activity or HAQ (allP>0.05).Conclusion:Synovial CD163+ macrophages are associated with radiographic joint destruction, which imply that CD163+ macrophages may play role in the pathogenisis of joint destruction in RA.Figure 1.Representative immunohistochemical findings of synovial CD163 expression. (A) Synovial CD163 expression in an Orth.A patient, an OA patient and a RA patient. (B) Densities of lining and sublining CD163+ macrophages in Orth.A, OA and RA patients.Figure 2.Spearman’s rank correlation analysis for synovial macrophages and mTSS in RA. (A) Correlation between sublining CD163+ macrophages and mTSS, joint space narrowing subscore, joint erosion subscore. (B) Correlation between lining CD163+ macrophages and mTSS, joint space narrowing subscore, joint erosion subscore.Funding: :This work was supported by National Natural Science Foundation of China (no. 81801606 and 81971527), Guangdong Natural Science Foundation (no. 2017A030313576, 2018A030313541 and 2019A1515011928).Figures:Disclosure of Interests:None declared