The use of composite disease activity scores enables a pragmatic approach to the measurement of the level of disease activity in children with juvenile idiopathic arthritis (JIA). These tools are constructed through the combination of individual measures and provide a quantification of the absolute level of disease activity in one summary number on a continuous scale. The first composite score for JIA, named Juvenile Arthritis Disease Activity Score (JADAS), was published in 2009. It includes the following four variables: physician global assessment, parent/patient global assessment, active joints count, and an acute phase reactant. Its score is calculated as the arithmetic sum of the scores of its four items. Additional versions of the JADAS, which lack the acute phase reactant (clinical JADAS, cJADAS) or are specific to systemic JIA (systemic JADAS, sJADAS), were developed over the years. An important progress in the field has been represented by the definition of the cutoff values in the JADAS that distinguish the states of inactive disease or minimal, moderate, and high disease activity in JIA. These cutoffs may serve as therapeutic targets in the treat-to-target strategy. Recently, a JADAS version entirely composed of parent/patient-reported outcome measures has been developed and validated. This tool is well suited to implement remote patient monitoring, a form of telemedicine that may help to optimize disease control and reduce the pressure on healthcare systems. This review is aimed to describe the different versions of the JADAS and the main aspects of their developmental process.

Gout is among the most prevalent etiologies of chronic inflammatory arthritis in the United States, which is characterized by monosodium urate (MSU) monohydrate crystals deposition in the tissues.[1][2] Gout was first recognized even before the common era. Hence it is arguably the most understood and manageable disease among all rheumatic diseases.[3][4] 

Background/Objectives: Serum neurofilament light chain (sNfL) is an early and sensitive biomarker of polyneuropathy. This study compared the UmanDiagnostics enzyme-linked immunosorbent assay (ELISA), and Meso Scale Discovery (MSD) R-PLEX assay with the current gold-standard single-molecule array (Simoa) assay for sNfL measurement. Methods: sNfL levels were measured with Simoa, ELISA, and MSD R-PLEX in 330 serum samples from 73 individuals with a pathogenic transthyretin gene variant (TTRv) and in 165 healthy controls (HC) with ELISA and MSD R-PLEX. Results: Median sNfL levels, assessed in serum samples from TTRv individuals, differed across all assays (all p < 0.001). Passing-Bablok regression slopes were 1.01 (Simoa-ELISA), 1.00 (Simoa-MSD R-PLEX), and 1.02 (MSD R-PLEX-ELISA), with very strong correlations (all r > 0.8). Bland-Altman analysis showed mean differences of 0.1 ± 0.2 pg/mL (Simoa-ELISA), 0.7 ± 0.1 pg/mL (Simoa-MSD R-PLEX), and -0.6 ± 0.2 pg/mL (MSD R-PLEX-ELISA). In HC, sNfL levels positively correlated with age. Z-score normalization allowed for inter-assay comparison. Conclusions: The ELISA and MSD R-PLEX assays provide suitable alternatives for the Simoa assay to measure sNfL levels in carriers of a pathogenic TTR-gene variant. The differences in concentrations defined by the assays directly relate to the internal standard provided with the assays.

Post-traumatic osteoarthritis (ptOA) following joint injury accounts for at least 12% of cases of symptomatic OA. Surgical restoration of joint biomechanics does not prevent ptOA development, suggesting other factors influence individual OA risk. One suggested factor is the immuno-inflammatory response in the joint, with both adaptive and innate immune responses implicated. Whether different joint injuries incite different acute inflammatory responses, potentially explaining variable ptOA risk, has not been explored. Male 10-12-week-old C57BL/6 mice were randomly assigned to one of 6 interventions: naïve non-operated-controls (NOC), sham surgery (SHAM), anterior cruciate ligament (ACL) sprain (ACLS - subcritical loading injury without ACL damage or ptOA development), ACLR (non-surgical ACL rupture), ACLT (surgical ACL transection), and surgical destabilization of the medial meniscus (DMM). Tissues were harvested at 8 time points spanning acute injury (day-1, -2, -7), and early (day-14), progressive (day-28, -42), and established/advanced (day-56, -70) ptOA development. Immune cells from the synovium and primary and secondary lymphatic organs were analysed using dedicated flow cytometry panels, and joints were evaluated using an established histopathological scoring system. Joint injuries that induced ptOA had a distinct spatiotemporal Th1 and Th 17 response in synovial tissue and draining lymph node with little systemic change. The Th1 response subsided once the cartilage damage reached its maximum, whereas Th17 cells continuously accumulated in the synovial tissue. Importantly, model-specific temporal differences in both Th1/Th2 and Th17/Treg cells were observed. Joint injury also led to a distinct pattern of monocyte cell numbers across tissues. In particular, a short-term (up to day-14) depletion of classically-activated Ly6Chigh monocytes in bone marrow and spleen was concordant with a synovial tissue influx indicating recruitment of systemic cells in ptOA-inducing injuries. This data indicates a predominant loco-regional and limited systemic response to joint injury. The magnitude and duration of the initial transient increase in activated-monocyte and M1 macrophages, and both acute and long-term Th1 and Th17 T-cell response, differentiated pt-OA-inducing from non-ptOA-inducing injury. Importantly, what you injure (ACL vs. meniscus) rather than how you injure it (surgery vs. non-surgical) determines the temporal pattern and systemic involvement of both the innate and adaptive immune response and the structural ptOA progression and severity.

Parvovirus B19 (B19V) is a common viral agent that may cause arthritis in adults. In rare cases, B19V has been associated with cryoglobulinaemic vasculitis. We report the case of a 47-year-old woman who presented with an acute febrile polyarthritis and palpable purpura on the lower limbs. Laboratory investigations revealed low complement C4, positive IgM and IgG for Parvovirus B19, and detectable serum cryoglobulins, which immunofixation was consistent with type III cryoglobulinemia. The patient responded favourably to corticosteroid therapy, with complete resolution of symptoms. One month after premature discontinuation of steroids, she experienced a relapse of polyarthralgia. A second course of low-dose corticosteroids led to sustained remission, without further relapse. In order to understand the clinical features of B19V-associated cryoglobulinaemic vasculitis, we conducted a narrative review of the literature using the PubMed database, in which we identified seven cases. The most frequent features included constitutional symptoms, cutaneous vasculitis, joint involvement and complement consumption. One previous case clearly identified type III cryoglobulinemia. These findings highlight the clinical heterogeneity of this entity and the importance of considering B19V in the differential diagnosis of small-vessel vasculitis with cryoglobulinemia, particularly in seronegative patients for hepatitis C and autoimmune diseases.

Rheumatoid arthritis (RA) is a systemic inflammatory condition that can lead to increased death rates, severe disability, and destructive joint damage. The prevalence of RA is the most frequent of all inflammatory diseases and is reported to affect 0.1-2.0% of the population worldwide. The incidence and disability-adjusted life years rates of RA in India have shown an increasing trend from 1990 to 2021. In the current investigation, a pharmacoinformatics approach was used to explore the potential synthetic derivative compounds of curcumin against unexplored hub genes associated with the therapeutics of RA in the Indian population. Such investigations could not only cut short the in-vitro and in-vivo experimental approaches. Herein, a GWAS of RA was conducted in a genetically distinct Indian population. CD4, STAT4, and CCR6 genes were identified and reconfirmed by a few previously reported GWAS findings, which revealed CCR6 as one of the key targets associated with RA. Lipinski's rule was used to determine the adsorption, distribution, metabolism, and excretion of ligands for drug suitability, and acute toxicity was also predicted. However, further docking analysis was carried out for curcumin and its nine derivatives against CCR6, STAT4, and CD4 human proteins compared with standards, i.e., Methotrexate and Hydroxychloroquine. Based on molecular docking, toxicity, and pharmacokinetics, the MD simulation study was observed for CCR6, STAT4, and CD4 with Methotrexate complex, Hydroxychloroquine complex, and pentagamavuton complex, respectively. This study revealed pentagamavuton as an active therapeutic that majorly inhibits the activity of the pivotal receptor CCR6, STAT4, and CD4 in humans.