Screening of potentially active compounds against rheumatoid arthritis in the Juan-Bi decoction using systems pharmacology and animal experiments.

Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear. Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches. Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound-target-pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collagen-induced arthritis (CIA) mouse models. Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis. Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms.

Experiences of Chinese Rheumatoid Arthritis Patients Who Chose Western Medicine, Traditional Chinese Medicine, and a Combination of Treatments: A Study Based on Interviews and Thematic Analysis.

Background: This qualitative study, part of a prospective mixed-methods research, aimed to gain insights into the medical experiences and disease perceptions of Chinese patients living with rheumatoid arthritis (RA). Specifically, the study examined how RA patients' perceptions of their disease were influenced by the diagnosis and treatment they receive. Methods: RA patients undergoing treatment were invited to participate in this qualitative study. Face-to-face semi-structured interviews were conducted among 18 patients, and the collected data were analyzed using thematic analysis. Results: The 18 participants in this study had a mean (SD) age of 58, a median disease duration of 6.5 years, and a predominance of female subjects (17 out of 18). The qualitative analysis identified two themes with six sub-themes: 1. Patients' experiences of treatment: discovery of the disease, misdiagnosis and mistreatment, and patients' treatment choices; 2. Feelings about the disease: psychological impact, reflections on the disease, and expectations of treatment. Conclusion: This study provides valuable perspectives and data to enhance the understanding of the relationship between patients' illness perceptions and their healthcare choices.

Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition.

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.

From psoriasis to psoriatic arthritis: epidemiological insights from a retrospective cohort study of 74,046 patients.

Introduction: To verify our hypothesis that psoriatic arthritis (PsA) is mainly genetically predetermined and distinct from psoriasis (PsO), we use the TriNetX database to investigate whether intrinsic factors outweigh externals in PsA emergence in PsO patients. Methods: We conducted three retrospective cohort studies utilizing information from the TriNetX network, whether (a) PsO patients with type 2 diabetes mellitus (DM) face an elevated risk of developing PsA compared to those without type 2 DM; (b) PsO patients who smoke face a higher risk of PsA; and (c) PsO patients with type 2 DM who smoke are more likely to develop PsA than those who do not smoke. Results: PsO patients with type 2 DM exhibited an elevated risk of developing PsA [hazard ratio (HR), 1.11; 95% CI 1.03-1.20], with the combined outcome demonstrating a heightened HR of 1.31 (95% CI 1.25-1.37). PsO patients with a smoking history exhibited an elevated risk of developing PsA (HR, 1.11; 95% CI 1.06-1.17), with the combined outcome demonstrating a heightened HR of 1.28 (95% CI 1.24-1.33). PsO patients with type 2 DM and a history of smoking were not found to be associated with an increased risk of developing PsA (HR, 1.05; 95% CI 0.92-1.20). However, the combined result revealed a higher risk of 1.15 (95% CI 1.06). Discussion: These findings suggested that intrinsic factors outweigh external factors in PsA emergence in PsO patients. Further studies may focus on genetic disparities between PsO and PsA as potential risk indicators rather than solely on phenotypic distinctions.

Luobitong Potentiates MTX's Anti-Rheumatoid Arthritis Activity via Targeting Multiple Inflammatory Pathways.

Background: The LuoBiTong (LBT) capsule, a novel traditional Chinese medicine formulation, is currently in Phase III clinical trials. Preliminary preclinical and Phase II clinical studies suggest its efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying mechanisms of its action remain to be elucidated.This research aims to explore the effects and mechanisms of LBT in conjunction with a maintenance dose of methotrexate (M-MTX) on RA. Methods: A Collagen-Induced Arthritis (CIA) mouse model was used to evaluate the anti-RA effects of LBT combined with M-MTX. Assessments included foot swelling, arthritis scoring, serum inflammatory factor analysis, and histopathological examination of the foot. These effects were compared with those of high-dose MTX (H-MTX). Network pharmacology was employed to construct a compound-target network for RA, based on drug composition, to predict its potential mechanism of action. Flow cytometry, Western Blot, and immunohistochemical analyses in animal models identified multiple inflammatory pathways targeted by LBT to augment the anti-RA effects of MTX. Results: The study revealed that LBT combined with M-MTX significantly alleviated CIA-induced arthritis without adverse effects. The combination of LBT and M-MTX showed similar or superior efficacy in regulating macrophage polarization, NF-κB, MAPK signaling pathways, and in the suppression of TH-17 expression in proinflammatory cells. These findings suggest that LBT may exert a multi-pathway therapeutic effect in RA treatment. The predicted pharmacological targets and mechanisms align well with this hypothesis. Conclusion: LBT, when combined with MTX, enhances the anti-RA effect by targeting multiple inflammatory pathways, demonstrating significant therapeutic potential.

Psoriatic arthritis, biologic therapy experience, body mass index, and onset age of psoriasis were independent factors of secukinumab discontinuation in patients with psoriasis.

INTRODUCTION: Despite the availability of several treatments for psoriasis (PsO), factors influencing the persistence of secukinumab (SEC) therapy remain inadequately understood. This study aimed to identify predictors of SEC persistence in PsO. METHODS: A retrospective analysis was conducted on 109 PsO patients who received SEC treatment at least 1 year. Patients were categorized based on continued or discontinued SEC therapy. RESULTS: Among the 109 patients, 64 continued SEC treatment while 45 discontinued. Univariate analysis demonstrated that PsA presence and previous biologic therapy use increased the risk of SEC discontinuation 3.56- and 2.33-fold (p = 0.001, %95 CI: 1.66-7.65 and p = 0.032, %95 CI: 1.08-5.04, respectively). Additionally, the risk of SEC discontinuation is 57% higher in patients with a body mass index (BMI) above 26.5 compared to those with a BMI below 26.5 (p = 0.016, %95 CI: 0.22-0.85). Additionally, patients with PsO onset age below 26.5 years were found to have a 2.93-times higher risk of discontinuing SEC compared to those with PsO onset age above 26.5 years (p = 0.004, %95 CI: 1.40-6.13). CONCLUSION: PsA presence, previous biologic therapy experience, BMI, and PsO onset age were identified as independent predictors of SEC discontinuation. These findings underscore the importance of personalized treatment strategies for PsO patients receiving SEC therapy.

What role do socioeconomic and clinical factors play in disease activity states in rheumatoid arthritis? Data from a large UK early inflammatory arthritis audit.

BACKGROUND: Persistently active rheumatoid arthritis (pactiveRA) may be due to the interplay between biological and non-biological factors. The role of socioeconomic factors remains unclear. OBJECTIVES: To explore which biological and non-biological factors associate with pactiveRA. METHODS: Adults with early RA in the National Early Inflammatory Arthritis Audit, recruited from May 2018 to October 2022, were included if having pactiveRA or persistently low RA (plowRA). The pactiveRA was defined as three consecutive Disease Activity Score-28 joints (DAS28) of >3.2 at baseline, 3 and 12 months. The plowRA was defined as DAS28 ≤3.2 at 3 and 12 months. Stepwise forward logistic regression was used to explore associations with pactiveRA (outcome). Age and gender were included a priori, with socioeconomic factors and comorbidities as exposure variables. RESULTS: 682 patients with pactiveRA and 1026 plowRA were included. Compared with plowRA, patients with pactiveRA were younger (58, IQR: 49-67) versus (62, IQR: 52-72), and included more women (69% vs 59%). The pactiveRA was associated with worse scores in patient-reported outcomes at baseline, and anxiety and depression screens. Overall, there was clear social patterning in pactiveRA, with age-by-gender interaction. Logistic regression indicated age, gender, social deprivation and previous or current smoking, were independently associated with pactiveRA, after controlling for disease severity markers (seropositivity). Depression, lung disease, gastric ulcers and baseline corticosteroid use, were also associated with pactiveRA (p<0.05 for all). CONCLUSION: Socioeconomic factors and deprivation were associated with pactiveRA, independent of clinical and disease characteristics. Identifying 'adverse' socioeconomic drivers of pactiveRA can help tailor interventions according to individual need.

"Inflammatory or non-inflammatory pain in inflammatory arthritis - How to differentiate it?"

Pain is a significant issue in rheumatoid arthritis (RA) and psoriatic arthritis (PSA) and can have a negative impact on patients' quality of life. Despite optimal control of inflammatory disease, residual chronic pain remains a major unmet medical need in RA. Pain in RA can be secondary to inflammation but can also generate neuroendocrine responses that initiate neurogenic inflammation and enhance cytokine release, leading to persistent hyperalgesia. In addition to well-known cytokines such as TNFα and IL-6, other cytokines and the JAK-STAT pathway play a role in pain modulation and inflammation. The development of chronic pain in RA involves processes beyond inflammation or structural damage. Residual pain is often observed in patients even after achieving remission or low disease activity, suggesting the involvement of non-inflammatory and central sensitization mechanisms. Moreover, fibromyalgia syndrome (FMS) is prevalent in RA patients and may contribute to persistent pain. Factors such as depression, sleep disturbance, and pro-inflammatory cytokines may contribute to the development of fibromyalgia in RA. It is essential to identify and diagnose concomitant FMS in RA patients to better manage their symptoms. Further research is needed to unravel the complexities of pain in RA. Finally, recent studies have shown that JAK inhibitors effectively reduce residual pain in RA patients, suggesting pain-reducing effects independent of their anti-inflammatory properties.

Magnetic Resonance Imaging Assessment of Ulnar Wrist Pain: A Practical Guide for Surgeons.

Ulnar-sided wrist pain is a challenging clinical scenario due to multiple overlapping pathologies and involved anatomic structures. Advanced imaging such as magnetic resonance imaging can be used as an effective diagnostic adjunct if interpreted correctly. In this article, clinically relevant structures and radiographic correlates of the ulnar wrist are discussed and a corresponding systematic approach to reviewing magnetic resonance imaging is presented.

Single-cell transcriptomic analysis to identify endomembrane regulation of metalloproteins and motor proteins in autoimmunity.

TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and mitochondria) and phagosomes. Activation of the immune system requires trafficking of various cargos between the endomembrane system and cell plasma membrane. The Golgi apparatus is the hub of the endomembrane system and essential for the generation, maintenance, recycling, and trafficking of the components of the endomembrane system itself and immune system. Intracellular trafficking and secretion of immune system components depend on mitochondrial metalloproteins for ATP synthesis that powers motor protein transport of endomembrane cargo. Glycan modifying enzyme genes and motor proteins are essential for the activation of the immune system and trafficking of antigens between the endomembrane system and the plasma membrane. Recently, TMEM230 was identified as co-regulated with RNASET2 in lysosomes and with metalloproteins in various cell types and organelles, including mitochondria in autoimmune diseases. Aberrant metalloproteinase secretion by motor proteins is a major contributor to tissue remodeling of synovial membrane and joint tissue destruction in rheumatoid arthritis (RA) by promoting infiltration of blood vessels, bone erosion, and loss of cartilage by phagocytes. In this study, we identified that specific glycan processing enzymes are upregulated in certain cell types (fibroblast or endothelial cells) that function in destructive tissue remodeling in rheumatoid arthritis compared to osteoarthritis (OA). TMEM230 was identified as a regulator in the secretion of metaloproteinases and heparanase necessary tissue remodeling in OA and RA. In dendritic (DC), natural killer and T cells, TMEM230 was expressed at low or no levels in RA compared to OA. TMEM230 expression in DC likely is necessary for regulatory or helper T cells to maintain tolerance to self-antigens and prevent susceptibility to autoimmune disease. To identify how TMEM230 and the endomembrane system contribute to autoimmunity we investigated, glycan modifying enzymes, metalloproteinases and motor protein genes co-regulated with or regulated by TMEM230 in synovial tissue by analyzing published single cell transcriptomic datasets from RA patient derived synovial tissue.

Core items to be included in a definition of moderate psoriatic arthritis: literature review and expert opinion.

Evidence-based treatment recommendations for psoriatic arthritis (PsA) suggest that treatment should be individualised but acknowledge the difficulty of correctly defining levels of activity (mild, moderate and severe). The aim of this study was to define the parameters or disease characteristics that should be included in a future definition of moderate PsA. Mixed. methods: (1) literature review to identify previous assessment tools used to classify patients into mild, moderate and severe forms, and (2) survey of rheumatologists, and experts in PsA, to obtain their opinion on the degree of validation and applicability of published definitions and tools, and on the parameters that should be included in a future definition of moderate PsA. We propose eight domains/items to be included in a definition of moderate PsA: number of active joints and inflamed entheses, physician global assessment (by visual analogue scale), dactylitis, body surface area (BSA) affected by psoriasis, psoriasis in special locations, and absence of hip involvement. The Disease Activity Index for Psoriatic Arthritis (DAPSA) score would be supported as part of this definition, as would the Psoriatic Arthritis Impact of Disease (PsAID) index. This study proposes a set of items/domains to be included in a definition of moderate PsA based on literature and expert opinion, which can be the starting point for further development and validation studies of the proposed items.

Ultrasonographic evaluation of changes in the joint before and after intra-articular injection in children with juvenile idiopathic arthritis.

OBJECTIVE: The aim of this study is to ultrasonographically (US) evaluate the course of the knee joint in oligoarticular juvenile idiopathic arthritis (JIA) patients who received intra-articular steroid (IAS) application to the knee joint. METHODS: 237 knee joints of 175 patients with oligoarticular JIA were evaluated retrospectively. The patients were divided into two groups: those who received only IAS therapy and those who were methotrexate to IAS therapy. Synovial fluid grade changes, synovial proliferation in B mode examination and power Doppler (PD) changes were evaluated with musculoskeletal ultrasonography (MSUS) separately for each joint before the treatment and at the 2nd, 6th and 12th weeks of the treatment. RESULTS: The percentages of regression in synovial fluid grade at the second, sixth, and 12th weeks were respectively 73.4%, 88.6%, and 89.0% (n=174, 210, 211, respectively). Meanwhile, the percentages of regression in PD grade were 69.2%, 82.7%, and 84.0% (n=164, 196, 199, respectively). At the second, sixth and 12th weeks, the percentage of those with synovial fluid grade 0 was 24.1%, 54.9%, 73.4%, respectively (n=57, 130, 174, respectively), while the percentage of those with PD grade 0 was 39.7%, 67.9%, 80.6%, respectively (n=94,161,191, respectively). The percentage of those without synovial proliferation in the second, sixth and 12th weeks was found to be 26.2%, 54.9%, 73.8% respectively (n=62, 130, 175, respectively). The mean time to regression of synovial fluid, synovial proliferation, and PD in the only IAS group was significantly short. The percentage of synovitis regression was higher in the only IAS group at all weeks. This difference was especially more pronounced in the early period. When the 12th-week results were evaluated, there was no difference between the two groups. CONCLUSION: This study highlights the utility of MSUS in evaluating the early results of IAS therapy applied to the knee joint in oligoarticular JIA patients.

Sexuality and sexual dysfunction in patients with psoriatic arthritis: A cross-sectional study.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory disorder affecting the joints, skin and entheses. Despite the importance of the topic, few studies have investigated the association between PsA and sexual function. The purpose of this study was to assess sexuality and the prevalence of sexual dysfunction (SD) in patients with PsA. METHODS: This was an observational, cross-sectional single-center study on 23 PsA patients (male=12; female=11) evaluated with 2 male questionnaires (MSQ= Male Sexual Quotient, and IIEF=International Index of Erectile Function) and 2 female questionnaires (FSQ= Female Sexual Quotient, and FSFI=Female Sexual Function Index) validated for Brazilian Portuguese, in order to determine changes in sexual function. Clinical parameters, musculoskeletal activity and skin activity were also analyzed to identify factors associated with SD. RESULTS: The mean age was 52.1±9.7 years (males) and 49.1±9.6 years (females). Clinically, the patients had low skin and peripheral joint disease activity or were in remission. The mean time of PsA was 10±6.2 years, and 65.2% had a steady sexual partner. The mean MSQ score was 75.8±16.8. The prevalence of SD was 91.7% in men (IIEF), with a predominance of mild SD. The mean FSQ score was 64.9±24.1. The prevalence of SD was 72.7% in women (FSFI), with low domain scores. Also, a significant association was found between female age and total and domain-specific FSFI scores. PASI (Psoriasis Area and Severity Index) and the general satisfaction domain (IIEF) were significantly correlated. CONCLUSION: This study found a high prevalence of SD in PsA patients. Age had a negative impact on female sexual function. Physicians need to be more aware of SD in this population to provide early multidisciplinary treatment and minimize the impact of the disease on the quality of life of patients and their partners.

Gut microbiome-immune interactions and their role in rheumatoid arthritis development.

Objective: The primary objective is to study the impact of gut microbiota and their interactions with diverse immunological markers on the development of rheumatoid arthritis. Methods: This study was performed in Astana, Kazakhstan, and included 77 Kazakh female patients older than 18 years, who met the American College of Rheumatology 2010 classification criteria for rheumatoid arthritis (RA), and 113 healthy controls. The DNA was extracted from fecal samples obtained from all study participants for subsequent sequencing at the 16S rRNA gene V1-V3 locus, facilitating the analysis of the gut microbiome. The Multiplex immunoassay was employed to measure the concentrations of inflammatory cytokines, chemokines, and immunoglobulins in both fecal and plasma samples. Results: Our taxonomic analysis revealed significant differences in the composition of the gut microbiota between the healthy control cohort and the cohort with rheumatoid arthritis RA. Alpha diversity was significantly lower in the RA group. Lachnospiraceae were the most abundant taxon and found to be crucial, showing correlations with immunological markers such as IL5. Additionally, Lachnospiraceae and Oscillospiraceae exhibited the most predictable power and distinguished the composition of both study groups. Conclusion: Our study identifies key differences in the gut microbiome of RA patients, revealing distinct microbial patterns and specific taxa abundance. We highlight potential biomarkers in immunological and bacterial pathways, offering insights into RA development and indicating possibilities for personalized treatment.

Association Between the Dose of Tofacitinib and Risk of Herpes Zoster in Patients With Rheumatoid Arthritis: Analysis of Japanese Adverse Drug Event Report Data.

BACKGROUND: Tofacitinib is one of the Janus kinase inhibitors approved for the treatment of rheumatoid arthritis. The major adverse event of this drug is herpes zoster, which can lead to death in severe cases. The risk of herpes zoster has been studied at 10 mg/day of tofacitinib; however, 5 mg/day, which is recommended in patients with chronic kidney disease, is unclear. OBJECTIVE: To investigate whether 5 mg/day of tofacitinib reduced the risk of herpes zoster compared with 10 mg/day in rheumatoid arthritis patients. METHODS: We analyzed the Japanese Adverse Drug Event Report Data (JADER) database and compared the frequency of herpes zoster in rheumatoid arthritis patients treated with tofacitinib 5 mg/day and 10 mg/day. Multivariable logistic regression analysis was performed to identify the risk factors for herpes zoster in tofacitinib users. RESULTS: A total of 812 tofacitinib users with rheumatoid arthritis were identified, including 131 with herpes zoster. Disproportionality for herpes zoster was observed between 5 mg/day and 10 mg/day (reporting odds ratio (OR): 0.68, 95% confidence interval (CI): 0.47-0.98, P = 0.045). Multivariable logistic regression analysis showed that the risk of herpes zoster was significantly increased in female patients (OR: 1.87, 95% CI: 1.12-3.12, P = 0.016) and methotrexate users (OR: 1.69, 95% CI: 1.12-2.54, P = 0.013) and significantly decreased with tofacitinib 5 mg/day compared with 10 mg/day (OR: 0.62, 95% CI: 0.40-0.96, P = 0.032). CONCLUSION: We suggest that tofacitinib 5 mg/day may decrease the risk of herpes zoster compared with 10 mg/day in rheumatoid arthritis patients.

Parotid saliva and blood biomarkers in juvenile idiopathic arthritis in relation to temporomandibular joint magnetic resonance imaging findings.

BACKGROUND: Juvenile idiopathic arthritis (JIA) often affects the temporomandibular joint (TMJ) caused by an abnormal immune system that includes overactive inflammatory processes. Salivary biomarkers may be a powerful tool that can help establishing diagnosis, prognosis and monitor disease progress. OBJECTIVE: The objective was to investigate biomarkers in parotid saliva and blood plasma in relation to temporomandibular joint (TMJ) magnetic resonance imaging (MRI) findings in patients with JIA and healthy individuals. METHODS: Forty-five children aged 6 to 16 years with JIA and 16 healthy age- and sex-matched controls were included. Unstimulated parotid saliva samples and venous blood were collected. Biochemical analyses were performed for the cytokine biomarkers. The participants underwent MR imaging of the TMJs, where changes in the inflammatory and the damage domains were assessed. RESULTS: In the JIA patients, lower concentrations of IL-6R and gp130 were found in parotid saliva than in plasma. Higher concentrations of IL-6 were found in parotid saliva than in plasma. IL-6, IL-6R and gp130 in parotid saliva explained the presence of bone marrow oedema and effusion in the JIA patients. CONCLUSIONS: This study suggests that the IL-6 family in parotid saliva is associated with TMJ bone marrow oedema and effusion in patients with JIA, suggesting that IL-6 has promising properties as a parotid saliva biomarker for TMJ inflammatory activity.

[IL-17A and IL-17F: from discovery to target of biologics - an illustrative example of translational research]. / IL-17A et IL-17F : de la découverte au ciblage thérapeutique - Un exemple de médecine translationnelle.

Interleukin (IL)-17A and then IL-17F have been discovered through their roles in chronic inflammatory diseases. These cytokines share 50% of sequence homology and bind to the same receptor made of the IL-17RA et IL-17RC chains. While they have rather similar pro-inflammatory effects, slight differences exist depending on the cell type considered or whether there is TNF or not. Indeed, there is a synergistic effect of TNF and IL-17A or IL-17F on many cell types. In addition, the interactions between immune and stromal cells also modulate their effects which vary according to stromal cell subtype. The identification of IL-17A and IL-17F roles in inflammatory diseases, as psoriasis, has led to the development of inhibitors of those cytokines. Anti-IL-17A, then anti-IL-17A/F and now anti-IL-17RA have been approved for different diseases and are particularly efficient in psoriasis. Their use is expending to other diseases like psoriatic arthritis and spondyloarthritis. Last, the recent understanding of the importance of stromal cells during chronic inflammation explains the relative inefficacy of such inhibitors in some other diseases.

Title: IL-17A et IL-17F : de la découverte au ciblage thérapeutique - Un exemple de médecine translationnelle. Abstract: L'interleukine (IL)-17A puis l'IL-17F ont été découvertes tour à tour pour leur rôle joué dans les maladies inflammatoires chroniques. Elles ont une homologie de séquence d'environ 50 % et partagent le même récepteur formé des chaînes IL-17RA et IL-17RC. Si elles ont des effets pro-inflammatoires assez similaires, il existe néanmoins quelques différences selon le type cellulaire considéré et selon la présence ou non de TNF, autre cytokine avec laquelle elles ont une synergie d'action. La troisième variable venant moduler leurs effets réside dans les interactions entre cellules immunes et cellules stromales, qui, là encore, varient selon le type de cellules stromales. La mise en évidence de leur rôle dans le psoriasis a notamment conduit au développement d'inhibiteurs de l'IL-17A, puis à la fois de l'IL-17A et de l'IL-17F et enfin d'un de leurs récepteurs. Ces inhibiteurs sont utilisés avec succès dans cette pathologie, et leur indication a été étendue progressivement au rhumatisme psoriasique et à certaines formes de spondylarthrite. Enfin, la récente compréhension de l'importance des cellules stromales dans la réaction inflammatoire chronique permet d'expliquer l'efficacité variable de ces biothérapies dans certaines pathologies.