Coziana Ciurtin

Objective: This study aimed to characterize whole blood transcriptomic profiles in adults with active Sjögren's disease (SjD) treated with anti‐CD20 or B lymphocyte stimulator/BAFF inhibition, identify markers of clinical response, and define inflammatory pathways linked to nonresponse. Methods: Whole blood RNA sequencing was performed at baseline and Week 24 in participants (n = 43) from a phase 2 GSK trial (NCT02631538) evaluating rituximab (RTX), belimumab (BEL), and sequential BEL‐RTX versus placebo. Differential expression (DESeq2; fold change >1.5; unadjusted P < 0.01) was integrated with pathway enrichment and ligand–receptor analyses (Metascape, gene set enrichment analysis, curated interaction databases). Clinical response was defined using EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Sjögren's Tool for Assessing Response (STAR); responder groups were compared using descriptive statistics, correlations, and logistic regression with receiver operating characteristic–based evaluation. Results: Sequential BEL‐RTX induced the largest transcriptional shift from baseline to Week 24. Baseline differential expression identified distinct ligand–receptor predictors for each response definition. ESSDAI nonresponse was associated with higher baseline transforming growth factor β‐2 (TGFβ‐2), C4A, and CD8A expression, and lower complement component 4 BP alpha (C4BPA) expression, defining complement‐regulated, cytotoxic, and stromal‐remodeling pathways (area under the curve [AUC] 0.89). In contrast, STAR nonresponders showed higher baseline expression of SPP1, TLR4, IL1R1, IL18R1, IL1RAP, TREM1, and FCGR2A, forming an IL‐1/IL‐18/FcγR‐centered myeloid module (AUC 0.80). No ligand–receptor genes overlapped between ESSDAI and STAR. ESSDAI genes clustered nonresponders distinctly, whereas STAR genes showed weak separation with no cluster concordance between the two response definitions. Conclusion: The distinct ESSDAI and STAR ligand–receptor signatures indicate different systemic biologic drivers of nonresponse to B cell therapies in SjD. Their complete nonoverlap suggests entrenched B cell–independent inflammatory circuits, highlighting complement regulation, TGFβ‐2–mediated remodeling, IL‐1/IL‐18 signaling, and FcγR activation as rational treatment pathways beyond B cell–targeted therapies. image

Objectives: Fatigue is an important and distressing symptom for many people living with chronic musculoskeletal (MSK) conditions. Non-pharmacological interventions designed to reduce fatigue have been investigated but the evidence is disparate across MSK conditions and across the lifespan. This scoping review aimed to create an overview of the current knowledge of non-pharmacological interventions for fatigue in MSK conditions across the lifespan, including their theoretical bases, the characteristics of participants and the clinical competencies of those delivering interventions. It aimed to use these findings to identify priorities for research and practice in collaboration with patient and public involvement groups. Design: A scoping review following the Joanna Briggs Institute methodology. Data sources: AMED, MEDLINE, PsycINFO, CINAHLPlus (EBSCO platform), EMBASE (Ovid platform), SCOPUS and Cochrane databases were searched for studies published between 1 January 2007 and 1 February 2026. Eligibility criteria for selecting studies: Peer-reviewed primary research studies describing a non-pharmacological intervention with either the intention or effect of reducing MSK fatigue and its impact were included. Data extraction and synthesis: Title and abstract and subsequent full-text review were performed by two independent reviewers in duplicate. Data were charted in categories according to types of intervention, participant characteristics and theoretical bases. Descriptive analysis of the results is presented. Results: 337 studies met the criteria. Conditions most frequently studied included fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus. Physical activity was the most common intervention type, most participants were adults and approximately 82% were female. 245 studies reported single component interventions, and 80 included a theoretical basis or the clinical competencies required to deliver them. Common exclusion criteria were physical comorbidities, psychiatric disease or unstable health conditions and cognitive impairments. Conclusions: Few studies have examined how combining single-component interventions can support person-centred fatigue management, and many populations have been excluded from research. To tailor interventions for people with MSK conditions, it is essential to understand how individual characteristics interact with health needs, define the underlying theory, identify the clinical skills required for effective delivery and have more inclusive inclusion criteria.

Sex differences in autoimmunity are among the most striking in human disease, yet they are often presented as fixed biological constants. A life course perspective reveals that sex bias emerges, intensifies or attenuates across developmental stages, shaped by interactions between sex chromosomes, hormonal transitions, immune maturation, environmental exposures and structural biases in research and clinical practice. We aimed to synthesise current evidence on sex bias in autoimmunity across the life course and to provide practical guidance for improving terminology, study design, reporting and interpretation in sex-aware autoimmune research. This narrative review integrates findings from immunology, endocrinology, epidemiology and methodological literature. Particular emphasis was placed on developmental transitions, including prepubertal, pubertal, reproductive, postpartum, menopausal and ageing stages and on identifying modifiable sources of bias in research practice. Sex differences in autoimmunity vary substantially across the lifespan. Early life immune programming, puberty-related hormonal shifts, reproductive transitions, pregnancy and postpartum immune modulation and menopause all contribute to dynamic patterns of disease susceptibility and expression. Structural factors, including diagnostic bias, sampling bias and insufficient sex stratified analyses, frequently distort interpretation of biological differences. Current research practices often conflate sex and gender, underpower sex-specific analyses and fail to report sex-disaggregated outcomes, limiting scientific rigour and clinical applicability. Sex bias in autoimmunity is not static but evolves with developmental and hormonal transitions. Addressing this complexity requires deliberate changes in research practice. Embedding a life course framework is essential for improving the accuracy, relevance and translational value of autoimmune research.

Pain is a frequent symptom in people with inflammatory arthritis (IA), which has substantial impact on their quality of life. Analyses of electronic health record data indicate that UK pain care in people with IA often involves prescribing long-term opioids and gabapentinoids, despite absent trial evidence for efficacy. Patient survey data suggest that non-pharmacological pain care with supportive trial evidence is underused. A UK-specific guideline on pain management for people with IA is required to address this. This comprehensive life-course guideline is the first British Society for Rheumatology Guideline to specifically address pain in people with IA. It provides evidence-based recommendations on how pain can be best managed in people with IA. It was developed using the methods outlined in the British Society for Rheumatology’s ‘Creating Clinical Guidelines’ protocol by a multidisciplinary Guideline Working Group, comprising healthcare professionals with expertise in paediatric and adult rheumatology and people with lived experience. By undertaking and considering the evidence from several systematic literature and umbrella reviews, 23 recommendations were developed. These address how pain should be assessed in people with IA alongside the role of the following treatments in IA pain management: DMARDs, glucocorticoids, analgesics, neuromodulators, exercise and physical activity, psychological interventions, ergonomic and orthotic interventions (excluding orthoses for foot pain), education, weight management and diet, addressing sleep problems, fatigue management, digital technologies and medical devices, complementary therapies, and support from others. An audit tool is provided to support the Guideline’s implementation, and key recommendations made for future research.

Objectives: Delays in Juvenile Idiopathic Arthritis (JIA) diagnosis may impact long-term outcomes and health-related quality of life (HRQoL). This study investigated referral pathways, initial treatment patterns and changes in HRQoL among UK children and young people with JIA stratified by ethnic group and socioeconomic position. Methods: Treatment-naive children and young people diagnosed with JIA between 2001 and 2019 were recruited into the Childhood Arthritis Prospective Study (CAPS). Outcomes included duration to first appointment, and change in HRQoL and disease activity following initial presentation. Associations between duration, presentation, and referral source with ethnicity and socioeconomic position, were assessed using adjusted Cox proportional hazards models. Results: Of 1275 patients, 65% were female, 91% White ethnicity (5% Asian, 1% Black, 3% Mixed), and 27% in the most deprived socioeconomic group. Median age was 8 years. Median time to first appointment was 18 weeks, varying slightly by ethnic group but not socioeconomic position. Referral source and initial treatment were similar across groups. While disease activity and HRQoL improved over the first 12 months following first appointment in paediatric rheumatology for individuals with JIA, the overall HRQoL measures remained below population norms for people without JIA, with limited improvement beyond 1 year. Ethnicity and socioeconomic position were not associated with time to appointment, initial treatment, or changes in disease activity or HRQoL. Conclusion: In this national inception cohort, ethnicity and socioeconomic position do not appear to be associated with access to specialist care, initial treatment, or early clinical outcomes. Persistent low HRQoL despite reduced disease activity highlights the need to address physical and psychosocial wellbeing beyond disease control.

Objectives: Juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM) are systemic autoimmune rheumatic diseases (RMDs) with childhood-onset associated with increased risk of damage accumulation and cardiovascular disease (CVD) over the life course. Methods: Damage associated with JSLE and JDM has been assessed using validated outcome measures in a longitudinal single-centre cohort study with long-term follow-up, involving data collected both retrospectively and prospectively. Descriptive statistics, sensitivity and regression analyses have been used to evaluate predictors of damage and CVD-risk. Results: We assessed comparatively a JSLE cohort (n=76), with a mean age of 24.3 ±4.2 years and a JDM cohort (n=79) with a mean 20.1 ± 5.0 years (p<0.001), with matched duration of follow-up (10.0 ± 4.2 vs. 11.0 ± 5.1, respectively, p=0.68). Traditional CVD-risk factors, including hypertension (p=0.02), dyslipidaemia (p=0.0005), and higher total cholesterol (p=0.01) and LDL-cholesterol (p=0.02) levels at the last assessment were higher in JSLE vs. JDM. Over the disease course, 39 (51.3%) AYA with JSLE vs. 47 (59.4%) AYA with JDM accumulated damage (p=0.307), which was independently predicted by the body mass index in both cohorts (p=0.038 and p=0.026, respectively). The PDAY score was the only tool able to stratify AYA based on CVD-risk (median = 5 (4-13) points in JSLE vs. 0 (0-3) points in JDM, p=0.0001), as all the adult CVD-risk scores were very low in both cohorts. Conclusions: This is the first comparative evaluation of JSLE vs. JDM in adulthood, which highlighted increased damage burden and CVD-risk in JSLE that warrants further investigation. Statement of clinical significance: No previous studies explored log-term outcomes and cardiovascular risk assessment in juvenile systemic lupus erythematosus (JSLE) compared to juvenile dermatomyositis (JDM), despite both conditions sharing pathogenic mechanisms, a significant risk of organ damage, and overlapping therapeutic approaches. Additionally, there is a scarcity of studies following children and young people into adulthood and none evaluating the performance of validated cardiovascular disease (CVD)-risk scores in these two conditions. This study provides the first comparative evaluation of organ specific damage accrual and their predictors, and CVD-risk drivers in JSLE vs. JDM in two cohorts with similar mean disease duration of over 10 years. Our results highlight similar prevalence of overall damage in both conditions, but with distinct organ and systems involvement, and significantly increased CVD-risk in JSLE. Interestingly, in addition to recognised predictors, the body mass index (BMI) was an independent predictor of damage in both cohorts, which emphasizes the need for better strategies to address modifiable contributors to damage accrual. This study raises awareness that CVD-risk scores validated for use in adult populations underperform in both JSLE and JDM in young adulthood, highlighting in parallel the potential clinical utility of a paediatric CVD-risk score (the PDAY score) for risk stratification in JSLE, as well as the need for more robust CVD-risk tools for adequate risk identification and tailored management strategies in JSLE and JDM later in life.

Objectives: Despite growing use of machine learning (ML) in medical research, evaluation of sex and ethnicity bias in systemic lupus erythematosus (SLE) models remains limited, underscoring a need for improved equity and model reliability. This study systematically reviewed ML models in SLE to assess bias and mitigation strategies and developed a GenAI proof-of-concept to automate and compare literature review performance. Methods: A manual PubMed review (Nov 2019-Nov 2024) assessed sex and ethnicity bias in original ML studies predicting clinically relevant SLE outcomes using a bias assessment scoring matrix and ML model quality criteria. GenAI applied the same criteria to free-access literature, enabling comparison of manual and AI-driven review methods. Results: Sex bias was assessed in 51 ML studies, with high reviewer agreement (κ=0.867). Over half (26, 51%) scored zero across all bias categories, and most failed to address sex skews in training/test datasets. Nearly all ignored sex-related variables, and none disaggregated performance by sex. Quality assessment showed moderate agreement (κ=0.767), with most studies rated medium quality (31, 60.7%), and few rated high (7, 13.7%) or low (13, 25.4%). Only 18 (35%) studies reported participant ethnicity and 15 (29%) considered it in ML models, with most failing to mitigate its impact. Conclusion: ML models in SLE largely overlook sex and ethnicity differences, risking inconsistent performance and health inequities. Investment in sex-disaggregated data and transparent AI development is essential. Our results demonstrate the potential to develop GenAI tools that automate bias detection and quality evaluation in medical ML studies.