PD-1 AGONISM INHIBITS ACTIVATION OF PLASMACYTOID DENDRITIC CELLS BY IN

in the study. All early RA pts and 4 SLE pts were not treated with glucocorticoids and disease-modifying antirheumatic drugs. Six SLE pts received low-dose glucocorticoids and hydroxychloroquine. All pts were assessed for macrophage activation and laboratory data: ESR, RF, ACCP, CRP, ANA, anti-dsDNA. Isolation of monocytes was carried out according to the standard procedure for obtaining a leukocyte fraction in a Ficoll gradient and subsequent selection of CD14 + cells using magnetic separation. After isola- tion, the cells were cultured in X-Vivo medium. To assess the degree of monocyte activation, cells were stimulated by the addition of LPS. The value of monocyte activation was expressed as a ratio of the level of secretion of proinflammatory cytokines by monocytes cultured with and without LPS addition. Secretion levels were determined by ELISA. The belonging of the isolated cells to CD14 + monocytes was additionally confirmed by flow cytometry. Results: Macrophage activation was 2.6 (2.0;5.4) and 4.8 (2.8;7.3) in RA and SLE pts, respectively (p>0.05). In RA and SLE pts macrophage activation was inde- pendent of age, sex, body mass index, traditional risk factors (arterial hyperten-sion, overweight, smoking, family history of cardiovascular diseases), RA activity scores (DAS28, SDAI), and SLADAI-2K. No association was found between macrophage activation and levels of ESR, RF, ACCP, CRP, ANA, and anti-dsDNA. Conclusion: No differences in macrophage activation were found in RA and SLE pts. Macrophage activation was independent of age, sex, traditional risk factors, and ARD-related parameters. A study on a larger number of pts will clarify the link between macrophage activation and autoimmune disorders. work Background: T cell function is regulated by complex signaling networks of intercon- nected activators and inhibitors. Blockade of inhibitory receptors such as programmed death-1 (PD-1) has emerged as a novel treatment for multiple forms of cancer. One of the most common adverse events associated with blockade of the endogenous PD-1/PD-L1 pathway is the induction of autoimmune pathology in multiple tissues, demonstrating that PD-1 activation is necessary for normal immune homeostasis in humans (Kostine, et al., 2018). Given this body of clinical data, we sought to develop a PD-1 agonist antibody as a therapeutic approach to restore immune homeostasis in patients living with autoimmune diseases. PD-1 expression and function has been primarily described on T cells (Ishida, et al., 1992), with additional data available from several other immune cell populations (Ohaegbulam, et al., 2015). Objectives: To study the effect of PD-1 agonism on plasmacytoid dendritic cell (pDC) function. Methods: Human PBMCs stimulated with or without toll-like receptor (TLR)-9 agonist, CpG were analyzed by flow cytometry for PD-1 expression on immune cell subsets. To assess the impact of PD-1 agonist on pDC function human PBMCs were activated by CpG in the presence or absence of PD-1 agonist. Type-I interferon (IFN) levels were quantified using ELISA from culture superna-tants. The expression of interferon stimulated genes was analyzed by qPCR as a measure of type-I Background: The development of new therapies to treat symptomatic osteoarthritis (OA) often requires targeting patient subgroups such as mild and/or moderate and/ or severe. Multiple assessments for pain are used in clinical and research settings, yet to quantify patient burden with increasing pain severity it is important to under-stand the potential variability in outcomes based on definitions of severity used 1 . Objectives: The objective of this study was to examine studies in the published literature that report the burden of OA pain by severity to assess similarities and/ or differences across study methodologies and outcomes. Methods: A targeted literature review of PubMed and Google Scholar was con- ducted January 2021 and included search terms: osteoarthritis, severity, United States (US), burden, quality of life, medication/treatment, and healthcare resource utilization. The search was limited to the English language, full-text articles, and no restriction on publication date. Results included a recent study of the burden of symptomatic OA pain respondents by severity level in the US 2,3 . Over 100 publication titles were reviewed. Comparison of findings was descriptive in nature. Results: Nine publications were identified representing 7 unique studies, 6 being patient and/or healthcare provider surveys. Two studies focused on OA severity: the remaining 5 stratified patients by pain severity, and all but 2 of the 5 identified and confirmed pain as OA-related. Pain measures included numeric rating scales (generic 0-10, Western Ontario and McMaster Universities Arthritis Index [WOMAC] NRS 3.1), visual analog scales (generic 0-100, Short-Form McGill Pain Question- naire Visual Analog Scale [SF-MPQ-VAS]) or Pain Interference with Activities (PIA) scale derived from the 12-Item Short Form Health Survey [SF-12v2] developed for the Medical Outcomes Study, with recall periods varying from 48 hours to 7 days to 4 weeks. Only one study exclusively assessed symptomatic patients only i.e., patients with pain scores of 0 were excluded; the remainder compared cohorts of no/mild pain with increasing severity cohorts. Four of the 7 studies examined pair- wise differences among mild, moderate, and severe patients (1 study vs. a non-OA cohort); 2 compared no/mild vs. moderate-to-severe OA pain and 1 study compared mild to moderate-to-severe OA pain. For most outcomes examined like clinical comorbidities, quality of life, and healthcare resource utilization, increasing burden was observed with increasing OA and/or pain severity despite study variability. Background: Disease modification is not yet possible for osteoarthritis (OA). Mitochondrial ROS and pro-inflammatory cytokines are involved in the patho-genesis of OA and are potential therapeutic targets. APPA, a combination of apo- cynin (AP) and paeonol (PA), has the potential capacity to modulate synthesis of pro-inflammatory stimuli. Objectives: To investigate the anti-inflammatory effect of APPA in human articular chondrocytes and cartilage. Methods: Tissue and chondrocytes from human OA cartilage were isolated. The effect of APPA on chondrocyte viability was analyzed using MTT. IL-1 β 10 ng/mL and LPS 10 ng/mL were used as pro-inflammatory stimuli. ROS production was evaluated by flow cytometry using DCFH-DA and MitoSoxRed. The percentage of senescent cells was evaluated through the quantification of Fluorescein di- β -D-ga-lactopyranoside (FDG) by flow cytometry. The effect of APPA on gene expression of pro-inflammatory cytokines (IL-8 and TNF- α ) and enzymes degrading cartilage (MMP-13 and MMP-3) were analyzed in chondrocyte and cartilage by RT-PCR. Quantification of Toluidine Blue (TB) staining in cartilage was performed to evaluate proteoglycans content using software ImageJ/Fiji. Release of Glycosaminoglycan (GAGs) into the supernatant was quantified using BlyscanTM Glycosaminoglycan assay. Statistical analyses were performed with GraphPad Prism v6. the incubation with IL-1 β (p=0.0018 and p=0.018 respectively). Quantification of release GAGs into the supernatant decreased significantly when the cartilage explants were incubated for 48h in presence of APPA 100 µg/mL (p=0.028). Conclusion: APPA has a clear anti-inflammatory effect on human articular chondrocytes, and could reduce extracellular matrix degradation of cartilage. This could be mediated by the capacity to modulate ROS production and reduce senescence. Background: Early recognition and treatment of inflammatory arthritis is imper- ative for the further course of the disease. Objectives: This study mean nodule serosal leukopenia (6 and lymphopenia were found in the with a biological in most patients The immunology results showed: positive anti-nuclear positive positive rheumatoid standard by joint pinching A joint