Role In Arthritis Research Articles

Development and Optimization of Guggal Extract Loaded Ultradeformable Vesicles using Central Composite Design for Improving Antioxidant Potential

Background: After almost 30 years of study, it is a scientific fact that inflammation is the root cause of arthritis. Objective: Guggul has a beneficial role in arthritis because of its ability to neutralize the NF-kappa factor. A topical drug delivery system is beneficial to overcome the problems associated with oral drug delivery and offers several potential advantages. Ultra-deformable vesicles (UDVs) are a special type of liposome made up of phospholipids and surfactants, and they are highly flexible. Methods: In the present investigation, 20 formulations were suggested by Design Expert® 10 software (Central Composite Design) which were prepared using film hydration method with lecithin (70-90 mg), tween 80 (10–30 mg), Guggul extract (3 mg) and sonicated for 5–15 minutes. The formulation was optimized based on particle size (R₁) and maximum entrapment efficiency (R2). Results: The optimized formulation consists of 78.92 mg soya phosphatidyl choline (lecithin), 22.08 mg Tween 80, and 3 mg Guggul with a sonication time of 12.74 minutes that resulted in a particle size of 375.5 ±15.1 nm and entrapment efficiency of 80.3 ± 3.1%. Guggul UDVs showed more antioxidant activity compared to Guggul extract, control and standard. Similar results were obtained in the case of anti-arthritic activity, which was measured by egg albumin denaturation, bovine serum albumin denaturation, proteinase inhibitory action, and anti-lipoxygenase activity. The data of both activities were analyzed using an unpaired t-test to determine significant values (p < 0.05). Conclusion: These results demonstrate the potential of UDVs in the treatment of all arthritis diseases.

SOXC Transcription Factors as Diagnostic Biomarkers and Therapeutic Targets for Arthritis

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common disorders that disrupt the quality of life of millions of people. These two chronic diseases cause damage to the joint cartilage and surrounding tissues of more than 220 million people worldwide. Sex-determining region Y-related (SRY) high-mobility group (HMG) box C, SOXC, is a superfamily of transcription factors that have been recently shown to be involved in various physiological and pathological processes. These include embryonic development, cell differentiation, fate determination, and autoimmune diseases, as well as carcinogenesis and tumor progression. The SOXC superfamily includes SOX4, SOX11, and SOX12, all have a similar DNA-binding domain, i.e., HMG. Herein, we summarize the current knowledge about the role of SOXC transcription factors during arthritis progression and their potential utilization as diagnostic biomarkers and therapeutic targets. The involved mechanistic processes and signaling molecules are discussed. SOX12 appears to have no role in arthritis, however SOX11 is dysregulated and promotes arthritic progression according to some studies but supports joint maintenance and protects cartilage and bone cells according to others. On the other hand, SOX4 upregulation during OA and RA was documented in almost all studies including preclinical and clinical models. Molecular details have indicated that SOX4 can autoregulate its own expression besides regulating the expression of SOX11, a characteristic associated with the transcription factors that protects their abundance and activity. From analyzing the currently available data, SOX4 seems to be a potential diagnostic biomarker and therapeutic target of arthritis.

Are we approaching a holistic view of leptin's role in arthritis?

Adipokines—in particular, leptin, the forerunner of this superfamily—are receiving increasing attention for their role in exerting both beneficial and harmful actions in musculoskeletal inflammatory diseases. Leptin has been extensively associated with cartilage metabolism and OA. OA human chondrocytes have been shown to produce higher levels of leptin than normal cartilage1, with the pattern of leptin expression related to the level of cartilage destruction2,3. Moreover, elevated leptin levels have been found in serum, IPFP, synovial tissues, and cartilage of OA patients compared with healthy controls4,5.

Calycosin represses AIM2 inflammasome-mediated inflammation and pyroptosis to attenuate monosodium urate-induced gouty arthritis through NF-κB and p62-Keap1 pathways.

Gouty arthritis is an inflammatory disease induced by monosodium urate (MSU), and is closely related to the activation of inflammasomes. Calycosin plays an anti-inflammatory role in arthritis. This study explored the mechanism of Calycosin in MSU-induced gouty arthritis. MSU-induced gouty arthritis mouse models with or without treatment of Calycosin were established, and physiological and pathological indicators were determined. Similarly, peripheral blood mononuclear cells (PBMCs) and THP-1 macrophages were used in vitro. Lactate dehydrogenase (LDH) was tested. The degree of centrifugal infiltration was detected by immunofluorescence. ELISA and quantitative reverse-transcription polymerase chain reactionwere conducted to determine the levels of inflammatory factors. Immunohistochemistry, immunofluorescence, and flow cytometry were utilized to detect the content of caspase-1. Protein expressions of NF-κB-, p62-Keap1 pathway-, and pyroptosis-related factors were examined by western blot. In MSU-induced mouse models, calycosin increased mechanical hyperalgesia but decreased the swelling index of the mouse knee joint in a time-dependent manner. MSU treatment increased inflammatory cells and LysM-eGFP+ neutrophils recruitment in vivo, and promoted the LDH content in vitro,and meanwhile, calycosin reversed the aforementioned effects of MSU. In addition, calycosin repressed the release of inflammatory factors, promoted p62 level and diminished the levels of AIM2, caspase-1, ASC, IL-1β, Keap1, Cleaved GSDMD, and Cleaved caspase-1 and phosphorylation of p65 and IκBα in MSU-induced mouse or cell models. Furthermore, AIM2 silencing also inhibited MSU-induced inflammation and pyroptosis. Collectively, calycosin may inhibit AIM2 inflammasomes-mediated inflammation and pyroptosis through NF-κB and p62-Keap1 pathways, ultimately playing a protective role in gouty arthritis.

Recent advances in enzyme-related biomaterials for arthritis treatment.

Arthritis is a group of highly prevalent joint disorders, and osteoarthritis (OA) and rheumatoid arthritis are the two most common types. The high prevalence of arthritis causes severe burdens on individuals, society and the economy. Currently, the primary treatment of arthritis is to relieve symptoms, but the development of arthritis cannot be effectively prevented. Studies have revealed that the disrupted balance of enzymes determines the pathological changes in arthritis. In particular, the increased levels of matrix metalloproteinases and the decreased expression of endogenous antioxidant enzymes promote the progression of arthritis. New therapeutic strategies have been developed based on the expression characteristics of these enzymes. Biomaterials have been designed that are responsive when the destructive enzymes MMPs are increased or have the activities of the antioxidant enzymes that play a protective role in arthritis. Here, we summarize recent studies on biomaterials associated with MMPs and antioxidant enzymes involved in the pathological process of arthritis. These enzyme-related biomaterials have been shown to be beneficial for arthritis treatment, but there are still some problems that need to be solved to improve efficacy, especially penetrating the deeper layer of articular cartilage and targeting osteoclasts in subchondral bone. In conclusion, enzyme-related nano-therapy is challenging and promising for arthritis treatment.

SCD13 role in arthritis mediated via bradykinin receptor.

sCD13 role in arthritis mediated via bradykinin receptor.

Production and Secretion of Gelsolin by Both Human Macrophage- and Fibroblast-like Synoviocytes and GSN Modulation in the Synovial Fluid of Patients with Various Forms of Arthritis.

Gelsolin (GSN) is an actin-binding protein involved in cell formation, metabolism and wound closure processes. Since this protein is known to play a role in arthritis, here we investigate how the synovial membrane with its specific synoviocytes contributes to the expression of GSN and how the amount of GSN expressed is modulated by different types of arthritis. Synovial membranes from adult healthy subjects and patients with rheumatoid arthritis (RA) and osteoarthritis (OA) are analyzed by immunofluorescence, Western blot and ELISA. Macrophage-like synoviocytes (MLS) and fibroblast-like synoviocytes (FLS) were isolated, cultured and analyzed for their potential to produce and secrete GSN. In addition, the GSN concentrations in the synovial fluid of various forms of arthritis are determined by ELISA. GSN is produced by the healthy and arthritic synovial membranes. Both forms of synoviocytes (MLS and FLS) release GSN. The results show that there is a significant reduction in GSN in the synovial fluid in adult patients with OA. This reduction is also detectable in adult patients with RA but is not as evident. In juvenile arthritis, there is a slight increase in GSN concentration in the synovial fluid. This study shows that primary MLS and FLS express GSN and that these cells, in addition to articular chondrocytes, contribute to GSN levels in synovial fluid. Furthermore, GSN concentrations are modulated in different types of arthritis. Further studies are needed to fully understand how GSN is involved in joint homeostasis.

Harnessing Inflammation Resolution in Arthritis: Current Understanding of Specialized Pro-resolving Lipid Mediators' Contribution to Arthritis Physiopathology and Future Perspectives.

The concept behind the resolution of inflammation has changed in the past decades from a passive to an active process, which reflects in novel avenues to understand and control inflammation-driven diseases. The time-dependent and active process of resolution phase is orchestrated by the endogenous biosynthesis of specialized pro-resolving lipid mediators (SPMs). Inflammation and its resolution are two forces in rheumatic diseases that affect millions of people worldwide with pain as the most common experienced symptom. The pathophysiological role of SPMs in arthritis has been demonstrated in pre-clinical and clinical studies (no clinical trials yet), which highlight their active orchestration of disease control. The endogenous roles of SPMs also give rise to the opportunity of envisaging these molecules as novel candidates to improve the life quality of rhematic diseases patients. Herein, we discuss the current understanding of SPMs endogenous roles in arthritis as pro-resolutive, protective, and immunoresolvent lipids.

The role of bacterial DNA containing CpG motifs in diseases.

Bacterial DNA containing unmethylated CpG motifs can activate immune cells to release proinflammatory cytokines. Here, the role of bacterial DNA containing CpG motifs in diseases with a focus on arthritis is discussed. Our studies demonstrate that the intraarticular injection of bacterial DNA and oligodeoxynucleotides containing CpG motifs (CpG ODN) induced arthritis. The induction of arthritis involves the role of macrophages over other cells such as neutrophils, NK cells, and lymphocytes. TNF-α and TNFRI play an important role in the development of arthritis. NF-κB also plays a critical regulatory role in arthritis. Systemic anti-inflammatory treatment, along with antibiotic therapy, has beneficial effects on the course and the outcome of bacterial arthritis. Thus, future treatment strategies for bacterial arthritis should include attempts to minimizing bacterial growth while blocking the proinflammatory effects of the bacterial DNA. Significant therapeutic efficiency has also been shown by CpG ODN-mediated Th1 immune activation in mouse models of cancer, infectious disease, and allergy/asthma.

Inhibitory activity of gintonin on inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and collagen-induced arthritis in mice

BackgroundGintonin is a newly derived glycolipoprotein from the roots of ginseng. The purpose of this study is to investigate the anti-arthritic efficacy of Gintonin on various proteases and inflammatory mediators that have an important role in arthritis. MethodsFibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β 1 hour later. The antioxidant effect of Gintonin was measured using MitoSOX and H2DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators using RT-PCR, western blot, and ELISA. The phosphorylation of mitogen-activated protein kinase (MAPK) pathways and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus were also analyzed using western blot, ELISA, and immunocytochemistry. Collagen-induced arthritis (CIA) mice model was used. Mice were orally administered with Gintonin (25, 50, and 100 mg/kg) every 2 days for 45 days. The body weight, arthritis score, squeaking score, and paw volume were measured as the behavioral parameters. After sacrifice, H&E and safranin-O staining were performed for histological analysis. ResultsGintonin significantly inhibited the expression of inflammatory intermediates. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. Moreover, Gintonin suppressed the symptoms of arthritis in the CIA mice model. ConclusionAs a result, the antioxidant and anti-inflammatory effects of Gintonin were demonstrated, and ultimately the anti-arthritic effect was proved. Collectively, Gintonin has a great potential as a therapeutic agent for arthritis treatment.

Bioactive role of plant stress hormone methyl jasmonate against lipopolysaccharide induced arthritis

The current investigation was carried out to screen antiarthritic potential of Methyl Jasmonate (MJ) against lipopolysaccharide (LPS) induced arthritis. Cartilage damage was induced in experimental animals by intraplantar administration of LPS (1 mg/kg) and antiarthritic effect of MJ was screened in two doses of MJ-1 (20 mg/kg), MJ-2 (40 mg/kg) by intraperitoneally administration. Indomethacin (30 mg/kg p.o.) was used as standard drug. The severity of arthritis was evaluated by assessing arthritis score, secondary lesions, motility test, stair climbing ability, and dorsal flexion pain score method. The estimation of blood cytokine tumor necrosis factor- aplha (TNF-α),interleukine (IL-2 and IL-6) and thymus/spleen index was carried out to access the severity of inflammation. Estimation of hepaticenzymatic antioxidant activity superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx)and radiological examination was carried out on 28th day. Results indicated that MJ showed significant reduction in severity of arthritis by decreasing arthritis score, secondary lesions where as significant increase in motility, climbing ability and flexion pain score was observed. Significant decreased in blood cytokine viz. TNF-α, IL-2, IL-6 andthymus/spleen index was observed in MJ treated animals in dose dependent manner. MJ treated animals showed significant increased and restoration of hepatic antioxidant enzymatic activityof SOD, CAT, GSH, GPx where asradiological examination indicates protective effect on joint structure as compared to LPS treated rats. These current studies conclude that MJ has protective role in arthritis.

Measuring Advanced/Extended Practice Roles in Arthritis and Musculoskeletal Care in Canada.

ObjectiveOur objective was to characterize Canadian workforce attributes of extended role practitioners (ERPs) in arthritis care.MethodsWe used an exploratory, mixed‐methods study that was based on the Canadian Rheumatology Association's Stand Up and Be Counted Rheumatologist Workforce Survey (2015). An anonymous online survey was deployed to groups of non‐physician health care professionals across Canada who potentially had post‐licensure training in arthritis care. Demographic and practice information were elicited. Qualitative responses were analyzed using grounded theory techniques.ResultsOf 141 respondents, 91 identified as practicing in extended role capacities. The mean age of ERP respondents was 48.7; 87% were female, and 41% of ERPs planned to retire within 5 to 10 years. Respondents were largely physical or occupational therapists by profession and practiced in urban/academic (46%), community (39%), and rural settings (13%). Differences in practice patterns were noted between ERPs (64.5%) and non‐ERPs (34.5%), with more ERPs working in extended role capacities while retaining activities reflective of their professional backgrounds. Most respondents (95%) agreed that formal training is necessary to work as an ERP, but only half perceived they had sufficient training opportunities. Barriers to pursuing training were varied, including personal barriers, geographic barriers, patient‐care needs, and financial/remuneration concerns.ConclusionTo our knowledge, no previous studies have assessed the workforce capacity or the perceived need for the training of ERPs working in arthritis and musculoskeletal care. Measurement is important because in these health disciplines, practitioners’ scopes of practice evolve, and ERPs integrate into the Canadian health care system. ERPs have emerged to augment provision of arthritis care, but funding for continuing professional development opportunities and for role implementation remains tenuous.

Phytol, a Chlorophyll Component, Produces Antihyperalgesic, Anti-inflammatory, and Antiarthritic Effects: Possible NFκB Pathway Involvement and Reduced Levels of the Proinflammatory Cytokines TNF-α and IL-6.

Phytol is a diterpene constituent of chlorophyll and has been shown to have several pharmacological properties, particularly in relation to the management of painful inflammatory diseases. Arthritis is one of the most common of these inflammatory diseases, mainly affecting the synovial membrane, cartilage, and bone in joints. Proinflammatory cytokines, such as TNF-α and IL-6, and the NFκB signaling pathway play a pivotal role in arthritis. However, as the mechanisms of action of phytol and its ability to reduce the levels of these cytokines are poorly understood, we decided to investigate its pharmacological effects using a mouse model of complete Freund's adjuvant (CFA)-induced arthritis. Our results showed that phytol was able to inhibit joint swelling and hyperalgesia throughout the whole treatment period. Moreover, phytol reduced myeloperoxidase (MPO) activity and proinflammatory cytokine release in synovial fluid and decreased IL-6 production as well as the COX-2 immunocontent in the spinal cord. It also downregulated the p38MAPK and NFκB signaling pathways. Therefore, our findings demonstrated that phytol can be an innovative antiarthritic agent due to its capacity to attenuate inflammatory reactions in joints and the spinal cord, mainly through the modulation of mediators that are key to the establishment of arthritic pain.

Ontogeny of Synovial Macrophages and the Roles of Synovial Macrophages From Different Origins in Arthritis.

The ontogeny of macrophages in most organ/tissues in human body has been proven. Due to the limited number and inaccessibility of synovial macrophages (SM), the origin of SM has not been fully illuminated. The objective of this study was designed to investigate the ontogeny of SM and to evaluate the role of SM from different origins in arthritis. Two origins of SM, embryonic SM (ESM) and bone marrow SM (BMSM) were identified in Cx3cr1-EGFP mice, CCR2−/− mice and bone marrow (BM) chimera model by using a stringent sorting strategy. The cellular features, including dynamic total cell number, in situ proliferation, phagocytosis and expressions of pro-inflammatory and anti-inflammatory genes, of ESM and BMSM were compared. In addition, ESM and BMSM showed different expression patterns in Rheumatoid Arthritis (RA) patients' synovium and during the developmental process of collagen-induced arthritis (CIA) mice. Taken together, these results demonstrated that the SM at least has two origins, ESM and BMSM. The different cellular property and dynamic expression patterns in RA patients/CIA mice highlight the notion that ESM and BMSM might play different role in arthritis.

Microbes play role in arthritis

People with aching joints and arthritis might be surprised to learn that their pain might start partly in the gut. Singapore-based researchers have shown that there is a link between autoimmune arthritis and the gut microbiome (Nat. Microbiol. 2019, DOI: 10.1038/s41564-019-0381-1). The human body is home to trillions of bacteria collectively known as microbiota. These bugs coexist with us and can release small molecules that circulate throughout the body, including bacterial peptidoglycans. These fragments of the bacterial cell wall are released when bacteria remodel their cells. Some are involved in immunostimulation, sleep promotion, and fever. Yue Wang’s team at the Institute of Molecular and Cell Biology decided to investigate the role of the circulating peptidoglycans in autoimmune arthritis. They found that increasing the amounts of peptidoglycans in the blood speeds up disease development in mice that are bred to have arthritis. But a single injection of a peptidoglycan antibody that

Epigenetic regulation of NfatC1 transcription and osteoclastogenesis by nicotinamide phosphoribosyl transferase in the pathogenesis of arthritis

Nicotinamide phosphoribosyltransferase (NAMPT) functions in NAD synthesis, apoptosis, and inflammation. Dysregulation of NAMPT has been associated with several inflammatory diseases, including rheumatoid arthritis (RA). The purpose of this study was to investigate NAMPT’s role in arthritis using mouse and cellular models. Collagen-induced arthritis (CIA) in DBA/1J Nampt+/− mice was evaluated by ELISA, micro-CT, and RNA-sequencing (RNA-seq). In vitro Nampt loss-of-function and gain-of-function studies on osteoclastogenesis were examined by TRAP staining, nascent RNA capture, luciferase reporter assays, and ChIP-PCR. Nampt-deficient mice presented with suppressed inflammatory bone destruction and disease progression in a CIA mouse model. Nampt expression was required for the epigenetic regulation of the Nfatc1 promoter and osteoclastogenesis. Finally, RNA-seq identified 690 differentially expressed genes in whole ankle joints which associated (P < 0.05) with Nampt expression and CIA. Selected target was validated by RT-PCR or functional characterization. We have provided evidence that NAMPT functions as a genetic risk factor and a potential therapeutic target to RA.

Methyl jasmonate a stress phytohormone attenuates LPS induced in vivo and in vitro arthritis.

The objective of present study was to screen the effect of methyl jasmonate (MJ) in lipopolysaccharide (LPS) induced in vivo and in vitro arthritis. Arthritis was induced in wistar rats by intraplantar administration of LPS (1mg/Kg) and effect of MJ was screened in two doses (20, 40mg/Kg, IP), indomethacin (30mg/Kg p.o) was used as standard. The anti-nociceptive effect was evaluated through behavioral assessment viz. cold allodynia, Paw thermal hyperalgesia and Tail cold hyperalgesia on 1st, 7th, 14th, 21st and 28th day. The Myeloperoxidase (MPO), Cathepsin D (CAT-D), articular elastase (ELA), and nitrite levels were estimated in articular cartilage tissues on the 28th day. Rat paw was subjected to histopathology after radiological examination on 28th day. In vitro effect of MJ was evaluated for three concentrations (5, 10, 20µg/ml) in LPS (1µg/ml) stimulated CHNO001 cells. Estimation of pro-inflammatory mediators was carried using ELISA. Significant reduction in pro-inflammatory mediators was observed in MJ treated chondrocyte cells. % proteinase inhibition was assessed for 10, 50, 100, 250, 500µg/mL and IC50 was found 266.15. MJ significantly reducesnociceptive response against hot and cold allodynia. Significant reduction in MPO, ELA, and nitrite levels was observed. The CAT-D levels significantly restored. Minimum focal mild infiltration of lymphocytes was observed at synovial area in standard and MJ treated rats. These current studies conclude that MJ has protective role in arthritis.

Microbiota-Dependent Involvement of Th17 Cells in Murine Models of Inflammatory Arthritis.

ObjectiveIntestinal microbiota are associated with the development of inflammatory arthritis. The aim of this study was to dissect intestinal mucosal immune responses in the preclinical phase of arthritis and determine whether the presence of Th17 cells, beyond involvement of the cytokine interleukin‐17 (IL‐17), is required for arthritis development, and whether the involvement of Th17 cells in arthritis depends on the composition of the host microbiota.MethodsMucosal T cell production of IL‐17, interferon‐γ, tumor necrosis factor α (TNFα), IL‐22, and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) was analyzed by flow cytometry and Luminex assay before arthritis onset in mice immunized to develop collagen‐induced arthritis (CIA). Pathogenic features of arthritis in mice with CIA and mice with antigen‐induced arthritis were compared between Th17 cell–deficient (CD4‐Cre + Rorc flox/flox) and Th17 cell–sufficient (CD4‐Cre − Rorc flox/flox) mice. In addition, the impact of intestinal microbiota on the Th17 cell dependence of CIA was assessed.ResultsLamina propria CD4 T cells were activated before the onset of arthritis in mice with CIA, with marked up‐regulation of several cytokines, including IL‐17A, TNFα, and GM‐CSF. CD4‐Cre + Rorc flox/flox mice showed a specific reduction in intestinal mucosal levels of Th17 cells and partially reduced levels of IL‐17–producing CD8 T cells. However, total levels of IL‐17A, mostly produced by γδ T cells and neutrophils, were unaffected. The severity of arthritis was significantly reduced in Th17 cell–deficient mice, suggesting that Th17 cells have additional, IL‐17A–independent roles in inflammatory arthritis. Accordingly, antigen‐stimulated T cells from Th17 cell–deficient mice produced less IL‐17A, IL‐17F, and GM‐CSF. Importantly, the dependence of CIA on the involvement of Th17 cells was mitigated in the presence of an alternative microbiome.ConclusionThese data from murine models suggest that activation of mucosal immunity precedes the development of arthritis, and also that Th17 cells have a microbiota‐dependent role in arthritis. Therefore, a microbiome‐guided stratification of patients might improve the efficacy of Th17‐targeted therapies.

Adverse effect of tocilizumab treatment on split thickness skin graft—a case report

Tocilizumab is a biological immunosuppressive drug used in the treatment of psoriasis arthritis. It works by blocking the interleukin 6 receptor and therefor blocking the immune response caused by IL-6 which plays an important role in arthritis. Tocilizumab is commonly used in RA patients who either have experienced insufficient effect of other treatment options or who have had unacceptable side effects from previous treatment. With this case report, we would like to raise awareness of a potentially previously unheard of adverse effect of tocilizumab treatment on split thickness skin graft (STSG). We present a case of a 61-year-old man, treated with tocilizumab for severe poly-articular, erosive psoriasis arthritis. He was diagnosed with BCC on the scalp and underwent excision followed by STSG with no complications. The patient experienced graft loss after commencing tocilizumab treatment days to weeks post grafting on numerous occasions. We find this possible adverse effect of tocilizumab on skin grafts to be of great importance to report as it is not previously mentioned in any literature. We hope that this case report will increase the awareness of this possible adverse effect on STSG in patients treated with tocilizumab (TCZ). As the patient is dependent on arthritis symptoms to be well controlled, it is of great importance to both medical and surgical teams responsible for treatment to be able to collaborate to plan best treatment, timing, and strategy.Level of Evidence: Level V, risk / prognostic study Level of Evidence: Level V, risk / prognostic study.

Properdin: A multifaceted molecule involved in inflammation and diseases

Properdin, the widely known positive regulator of the alternative pathway (AP), has undergone significant investigation over the last decade to define its function in inflammation and disease, including its role in arthritis, asthma, and kidney and cardiovascular diseases. Properdin is a glycoprotein found in plasma that is mainly produced by leukocytes and can positively regulate AP activity by stabilizing C3 and C5 convertases and initiating the AP. Promotion of complement activity by properdin results in changes in the cellular microenvironment that contribute to innate and adaptive immune responses, including pro-inflammatory cytokine production, immune cell infiltration, antigen presenting cell maturation, and tissue damage. The use of properdin-deficient mouse models and neutralizing antibodies has contributed to the understanding of the mechanisms by which properdin contributes to promoting or preventing disease pathology. This review mainly focusses on the multifaceted roles of properdin in inflammation and diseases, and how understanding these roles is contributing to the development of new disease therapies.