Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort.

Objective: Rheumatoid Arthritis (RA) often exhibits suboptimal treatment response despite early diagnosis and treatment. This study aimed to analyze Early Rheumatoid Arthritis (ERA) synovial biopsies through histology and immunohistochemistry (IHC) to identify predictive factors for treatment response to Methotrexate (MTX).

Methods: 140 ERA patients from the UCLouvain Arthritis Cohort underwent synovial biopsy and were monitored after initiating Disease-Modifying Antirheumatic Drug (DMARD) therapy.

Two Broad Categories Overlapping With Rheumatoid Arthritis Observed in Synovial Biopsies from Patients With Juvenile Idiopathic Arthritis.

Objective: The objective is to characterize transcriptomic profiles and immune cell composition and distribution in juvenile idiopathic arthritis (JIA) synovial biopsies, assess for associations of these features with clinical parameters, and compare JIA and rheumatoid arthritis (RA) synovial features.

Methods: RNA sequencing (RNASeq) was performed on 24 samples, with pathway analysis and inference of relative abundance of immune cell subsets based on gene expression data. Two multiplex fluorescence immunohistochemistry (IHC) panels were performed on 28 samples (including 13 on which RNASeq was performed), staining for CD206 classical and CD206 nonclassical macrophages, and CD8 and CD4 T and B lymphocytes.

Patterns and determinants of response to novel therapies in juvenile and adult-onset polyarthritis.

Biologic and targeted synthetic DMARDs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Among these, polyarticular JIA (pJIA) and RA display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, the therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA.

Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis.

Objectives: Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven approaches to define clinically relevant subgroups.

Methods: RNASeq was performed on 74 samples, with disease activity data collected at inclusion. Principal components analysis (PCA) and unsupervised clustering were used to define patient clusters based on expression of the most variable genes, followed by pathway analysis and inference of relative abundance of immune cell subsets.

Abatacept as Monotherapy and in Combination With Methotrexate in Patients With Juvenile Idiopathic Arthritis: Analysis of 2 Phase III Trials.

Objective: To describe the efficacy and safety data of children with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with abatacept (ABA) + methotrexate (MTX) or ABA monotherapy when prior MTX use was either ineffective or not tolerated.

Methods: Posthoc analysis of 2 phase III trials of subcutaneous (SC) and intravenous (IV) ABA over 2 years in patients with pcJIA (aged 2-17 years). Patients were stratified by treatment with ABA + MTX or ABA monotherapy and further by prior biologic use.

Pharmacovigilance pregnancy data in a large population of patients with chronic inflammatory disease exposed to certolizumab pegol.

Introduction: Chronic inflammatory diseases (CIDs), including rheumatic diseases and other inflammatory conditions, often affect women of reproductive age. Tumor necrosis factor inhibitors (TNFi) are widely used to treat CID, but there is limited information on outcomes of TNFi-exposed pregnancies. We evaluated pregnancy outcomes from 1392 prospectively reported pregnancies exposed to certolizumab pegol (CZP), a PEGylated, Fc-free TNFi with no to minimal placental transfer.

High p16, a marker of cellular senescence, is associated with renal injury, impairment and outcome in lupus nephritis.

Objectives: Because a significant fraction of patients with lupus nephritis (LN) develops renal impairment, there is a need to better understand the mechanisms underlying disease progression. Here, we assessed for cellular senescence in the LN kidney, and its association with disease severity and outcome.

Methods: We enumerated the number of cells positive for p16 protein, a marker of cellular senescence, by immunohistochemistry followed by digital quantification, on renal biopsies from 40 patients with active LN.

Canakinumab improves patient-reported outcomes in children and adults with autoinflammatory recurrent fever syndromes: results from the CLUSTER trial.

Objectives: To evaluate the effect of canakinumab on health-related quality of life (HRQoL), work/school and social life of patients with autoinflammatory recurrent fever syndromes, including colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and tumour necrosis factor receptor-associated periodic syndrome, in the CLUSTER trial.

Methods: HRQoL of patients who received canakinumab 150 mg or 300 mg every four weeks in the CLUSTER trial (n=173) was assessed at baseline and Weeks 17 and 41. For children we used the Child Health Questionnaire - Parent Form 50 (CHQ-PF50), including psychosocial (PsS) and physical (PhS) component summary scores.

Serum calprotectin (S100A8/A9): a promising biomarker in diagnosis and follow-up in different subgroups of juvenile idiopathic arthritis.

Introduction: In the management of juvenile idiopathic arthritis (JIA), there is a lack of diagnostic and prognostic biomarkers. This study assesses the use of serum calprotectin (sCal) as a marker to monitor disease activity, and as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA.

Methods: Eighty-one patients with JIA from the CAP48 multicentric cohort were included in this study, as well as 11 non-paediatric healthy controls.

Molecular Signatures of Kidney Antibody-Secreting Cells in Lupus Patients With Active Nephritis Upon Immunosuppressive Therapy.

Objective: This study was undertaken to characterize kidney and urine antibody-secreting cells (ASCs) from patients with active lupus nephritis, before and after induction therapy.

Methods: We included patients with biopsy-proven active lupus nephritis and performed anti-CD138 staining of kidney biopsy samples to visualize ASCs. We performed single-cell gene expression profiling on sorted ASCs from fresh biopsy samples using multiplex reverse transcriptase-polymerase chain reaction.

Paired Rheumatoid Arthritis Synovial Biopsies From Small and Large Joints Show Similar Global Transcriptomic Patterns With Enrichment of Private Specificity and TCR Signaling Pathways.

Objectives: We explored histological and transcriptomic profiles of paired synovial biopsies from rheumatoid arthritis (RA) patients, in order to assess homogeneity in synovial tissue at the individual level.

Methods: Synovial biopsies were performed simultaneously in one small and one large joint per patient using needle-arthroscopy for the knee and ultrasound-guided biopsy for the hand or wrist. Synovium from individuals with osteoarthritis was used as controls.

Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease characterized by the development of anti-nuclear antibodies. Susceptibility to SLE is multifactorial, with a combination of genetic and environmental risk factors contributing to disease development. Like other polygenic diseases, a significant proportion of estimated SLE heritability is not accounted for by common disease alleles analyzed by SNP array-based GWASs.

Efficacy and Safety of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis With and Without Fever at Baseline: Results From an Open-Label, Active-Treatment Extension Study.

Objective: To evaluate the long-term efficacy and safety of canakinumab and explore prediction of response in patients with systemic juvenile idiopathic arthritis (JIA) with or without fever at treatment initiation.

Methods: At enrollment, patients with active systemic JIA (ages 2 to <20 years) started open-label canakinumab (4 mg/kg every 4 weeks subcutaneously). Efficacy measures included the adapted American College of Rheumatology (ACR) Pediatric 50/70/90 criteria, the Juvenile Arthritis Disease Activity Score (JADAS), and clinically inactive disease and clinical remission on medication, evaluated by either the JADAS or ACR criteria.

Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome: Report of two new cases and literature review.

We herein report two new adolescent cases of Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome. This rare, recently described condition may be associated with postural orthostatic tachycardia syndrome (POTS) and other forms of orthostatic intolerance. This report provides details on two cases and a literature review.

Comparison of the disease activity score and the revised EUSTAR activity index in diffuse cutaneous systemic sclerosis patients.

Objectives: To compare the ability of the Disease Activity Score (DAS) and the Revised EUSTAR Activity Index (RAI) to detect diffuse cutaneous systemic sclerosis (dcSSc) patients requiring treatment intensification in a Belgian cohort.

Methods: We retrospectively compared the widely used DAS and the recently developed RAI in a longitudinal cohort (median follow-up of 42 months) of 62 dcSSc patients, of whom 30 with a disease duration ≤3 years at inclusion. Active disease was defined by a DAS ≥3/10 or a RAI ≥2.

Proteomic analysis in lupus mice identifies Coronin-1A as a potential biomarker for lupus nephritis.

Background: Approximately 50% of systemic lupus erythematosus (SLE) patients develop nephritis, which is among the most severe and frequent complications of the disease and a leading cause of morbidity and mortality. Despite intensive research, there are still no reliable lupus nephritis (LN) markers in clinical use that can assess renal damage and activity with a high sensitivity and specificity. To this end, the aim of this study was to identify new clinically relevant tissue-specific protein biomarkers and possible underlying molecular mechanisms associated with renal involvement in SLE, using mass spectrometry (MS)-based proteomics.

Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches.

Background: Pathogenesis and aetiology of systemic sclerosis (SSc) are currently unclear, thus rendering disease prognosis, diagnosis and treatment challenging. The aim of this study was to use paired skin biopsy samples from affected and unaffected areas of the same patient, in order to compare the proteomes and identify biomarkers and pathways which are associated with SSc pathogenesis.

Methods: Biopsies were obtained from affected and unaffected skin areas of SSc patients.

Tapering of biological antirheumatic drugs in rheumatoid arthritis patients is achievable and cost-effective in daily clinical practice: data from the Brussels UCLouvain RA Cohort.

Background/purpose: Studies have demonstrated that rheumatoid arthritis (RA) patients who achieve low disease activity or remission are able to taper biological disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to evaluate the proportion of patients in whom bDMARDs can be tapered in daily practice and to analyse the characteristics of these patients. Other objectives were to analyse which bDMARDs are more suitable for dose reduction and the cost savings.

Serum GlycA Level is Elevated in Active Systemic Lupus Erythematosus and Correlates to Disease Activity and Lupus Nephritis Severity.

Objective: Reliable non-invasive biomarkers are needed to assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). Glycoprotein acetylation (GlycA), a novel biomarker for chronic inflammation, has been reported to be increased in several inflammatory diseases. We investigated the relevance of serum GlycA in SLE patients exhibiting various levels of activity and severity, especially with regards to renal involvement.