Annals of the Rheumatic Diseases

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The indirect immunofluorescence assay (IIFA) on HEp-2 cells is widely used for detection of antinuclear antibodies (ANA). The dichotomous outcome, negative or positive, is integrated in diagnostic and classification criteria for several systemic autoimmune diseases. However, the HEp-2 IIFA test has much more to offer: besides the titre or fluorescence intensity, it also provides fluorescence pattern(s). The latter include the nucleus and the cytoplasm of interphase cells as well as patterns associated with mitotic cells...

OBJECTIVES: Nerve growth factor (NGF) has emerged as a key driver of pain in osteoarthritis (OA) and antibodies to NGF are potent analgesics in human disease. Here, we validate a novel vaccine strategy to generate anti-NGF antibodies for reversal of pain behaviour in a surgical model of OA. METHODS: Virus-like particles were derived from the cucumber mosaic virus (CuMV) and coupled to expressed recombinant NGF to create the vaccine. 10-week-old male mice underwent partial meniscectomy to induce OA or sham-surgery...

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common class of childhood rheumatic diseases, with distinct disease subsets that may have diverging pathophysiological origins. Both adaptive and innate immune processes have been proposed as primary drivers, which may account for the observed clinical heterogeneity, but few high-depth studies have been performed. METHODS: Here we profiled the adaptive immune system of 85 patients with JIA and 43 age-matched controls with indepth flow cytometry and machine learning approaches...

OBJECTIVES: To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months...

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OBJECTIVE: There is inconsistent evidence about the association between inflammatory disorders and depression and anxiety onset in a primary care context. The study aimed to evaluate the risk of depression and anxiety within multisystem and organ-specific inflammatory disorders. METHODS: This is a prospective cohort study with primary care patients from the UK Clinical Practice Research Datalink diagnosed with an inflammatory disorder between 1 January 2001 and 31 December 2016...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

OBJECTIVES: Osteoarthritis (OA) is a painful and debilitating disease and it is associated with aberrant upregulation of multiple factors, including matrix metalloproteinase 13 (MMP13), interleukin-1β (IL-1β) and nerve growth factor (NGF). In this study, we aimed to use the CRISPR/Cas9 technology, a highly efficient gene-editing tool, to study whether the ablation of OA-associated genes has OA-modifying effects. METHODS: We performed intra-articular injection of adeno-associated virus, which expressed CRISPR/Cas9 components to target each of the genes encoding MMP13, IL-1β and NGF, in a surgically induced OA mouse model...

In 2012, a European initiative called Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile localised scleroderma (JLS) is a rare disease within the group of paediatric rheumatic diseases (PRD) and can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. This study aims to provide recommendations for assessment and treatment of JLS...

OBJECTIVES: To evaluate the efficacy and safety of ianalumab (VAY736), a B cell-depleting, B cell activating factor receptor-blocking, monoclonal antibody, in patients with active primary Sjögren's syndrome (pSS) in a double-blind, placebo-controlled, phase II, single-centre study. METHODS: Patients with pSS, EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) ≥6, were randomised to ianalumab single infusion at either 3 mg/kg (n=6), 10 mg/kg (n=12) or placebo (n=9)...

OBJECTIVE: Gout is the most common inflammatory arthritis worldwide, and patients experience a heavy burden of cardiovascular and metabolic diseases. The inflammation is caused by the deposition of monosodium urate (MSU) crystals in tissues, especially in the joints, triggering immune cells to mount an inflammatory reaction. Recently, it was shown that MSU crystals can induce mechanistic target of rapamycin (mTOR) signalling in monocytes encountering these crystals in vitro. The mTOR pathway is strongly implicated in cardiovascular and metabolic disease...

OBJECTIVES: Early initiation of effective treatment favours remission in rheumatoid arthritis, but it remains unknown if the same concept applies to psoriatic arthritis (PsA). Therefore, this study investigated whether the combination of golimumab plus methotrexate (MTX) as a first-line treatment is superior to MTX alone in inducing remission in PsA. METHODS: This investigator-initiated, multicentre, double-blind, randomised, placebo-controlled trial included 51 MTX and bDMARD-naive patients with PsA fulfilling the CASPAR criteria and with active disease at baseline (≥3 swollen joint count/tender joint count)...

OBJECTIVE: We aimed to understand the role of the tyrosine phosphatase PTPN14-which in cancer cells modulates the Hippo pathway by retaining YAP in the cytosol-in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHODS: Gene/protein expression levels were measured by quantitative PCR and/or Western blotting. Gene knockdown in RA FLS was achieved using antisense oligonucleotides. The interaction between PTPN14 and YAP was assessed by immunoprecipitation...

OBJECTIVES: Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population. METHODS: The COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression...

OBJECTIVE: Congenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect for large groups of patients. We therefore used nation-wide healthcare registers to investigate comorbidity and outcomes in patients with CHB and their siblings. METHODS: Data from patients with CHB (n= 119) and their siblings (n= 128), all born to anti-Ro/SSA-positive mothers, and from matched healthy controls (n= 1,190) and their siblings (n= 1,071), were retrieved from the Swedish National Patient Register...

OBJECTIVES: To investigate a potential shared susceptibility between rheumatoid arthritis (RA) and acute coronary syndrome (ACS) by estimation of the risk of ACS among full siblings of patients with RA. METHODS: By linking nation-wide Swedish registers, we identified a cohort of patients with new-onset RA 1996-2016, age- and sex-matched (5:1) general population comparator subjects, full siblings of RA and comparator subjects, and incident ACS events through 31 December 2016...

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