Identification of a novel transcriptome signature for predicting the response to anti-TNF-α treatment in patients with rheumatoid arthritis.

Objectives: This study aims to identify and validate a transcriptomic signature capable of predicting the response to tumour necrosis factor inhibitors (TNFi) therapy in patients with rheumatoid arthritis (RA) before treatment initiation.

Methods: We performed a retrospective transcriptomic analysis using 2 public datasets, RNA-seq data from peripheral blood mononuclear cells (GSE138746) and microarray data from whole blood (GSE33377), to define a small-scale gene signature predictive of the response to TNFi treatment. Three external validations were then conducted, resulting in a total of 279 individuals, 169 responders, and 110 nonresponders.

Adipokines as potential pharmacological targets for immune inflammatory rheumatic diseases: Focus on rheumatoid arthritis, osteoarthritis, and intervertebral disc degeneration.

Adipokines are a heterogeneous group of signalling molecules secreted prevalently by adipose tissue. Initially considered as regulators of energy metabolism and appetite, adipokines have been recognized for their substantial involvement in musculoskeletal disorders, including osteoarthritis, rheumatoid arthritis, and many others. Understanding the role of adipokines in rheumatic inflammatory and autoimmune diseases, as well as in other musculoskeletal diseases such as intervertebral disc degeneration, is crucial for the development of novel therapeutic strategies.

Quantification of temporomandibular joint space in patients with juvenile idiopathic arthritis assessed by cone beam computerized tomography.

Objective: To describe a method to calculate the total intra-articular volume (inter-osseous space) of the temporomandibular joint (TMJ) determined by cone-beam computed tomography (CBCT). This could be used as a marker of tissue proliferation and different degrees of soft tissue hyperplasia in juvenile idiopathic arthritis (JIA) patients.

Materials And Methods: Axial single-slice CBCT images of cross-sections of the TMJs of 11 JIA patients and 11 controls were employed.

Asprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects.

Adipose tissue malfunction leads to altered adipokine secretion which might consequently contribute to an array of metabolic diseases spectrum including obesity, diabetes mellitus, and cardiovascular disorders. Asprosin is a novel diabetogenic adipokine classified as a caudamin hormone protein. This adipokine is released from white adipose tissue during fasting and elicits glucogenic and orexigenic effects.

WISP-2 modulates the induction of inflammatory mediators and cartilage catabolism in chondrocytes.

Wnt-1 inducible signaling pathway protein 2 (WISP-2/CCN5) is a recently identified adipokine that has been described as an important mediator of canonical Wnt activation in adipogenic precursor cells. In osteoarthritis (OA), the most common form of arthritis, chondrocytes exhibit aberrant and increased production of pro-inflammatory mediators and matrix degrading enzymes such as IL-1β and MMP-13. Although recent evidence suggests a role for Wnt signaling in OA physiopathology, little is known about the involvement of WISP-2 in cartilage degradation.

TMJ contrast enhancement in CBCT images using a new algorithm.

Magnetic resonance imaging (MRI) is considered the gold standard to reliably diagnose inflammation in the temporomandibular joint (TMJ) of patients with juvenile idiopathic arthritis (JIA). However, even MRI imaging is dependent on the familiarity of the radiologist with the normal appearance of the TMJ; therefore, new approaches are needed. Our purpose here is to improve imaging quality of cone beam computed tomography (CBCT) as a tool to help in the diagnosis of JIA in the TMJ.

Monomeric C reactive protein (mCRP) regulates inflammatory responses in human and mouse chondrocytes.

C-reactive protein (CRP) is an acute-phase protein that is used as an established biomarker to follow disease severity and progression in a plethora of inflammatory diseases. However, its pathophysiologic mechanisms of action are still poorly defined and remain elusive. CRP, in its pentameric form, exhibits weak anti-inflammatory activity.

HLA association with the susceptibility to anti-synthetase syndrome.

Objective: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD).

Methods: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing.

Results: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.

Levels of the Novel Endogenous Antagonist of Ghrelin Receptor, Liver-Enriched Antimicrobial Peptide-2, in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a debilitating, chronic, inflammatory, autoimmune disease associated with cachexia. The substitutive therapy of gut hormone ghrelin has been pointed at as a potential countermeasure for the management of metabolic and inflammatory complications in RA. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inverse agonist/antagonist of the ghrelin receptor makes feasible the development of a more rational pharmacological approach.

Molecular Relationships among Obesity, Inflammation and Intervertebral Disc Degeneration: Are Adipokines the Common Link?

Intervertebral disc degeneration (IVDD) is a chronic, expensive, and high-incidence musculoskeletal disorder largely responsible for back/neck and radicular-related pain. It is characterized by progressive degenerative damage of intervertebral tissues along with metabolic alterations of all other vertebral tissues. Despite the high socio-economic impact of IVDD, little is known about its etiology and pathogenesis, and currently, no cure or specific treatments are available.

Adipokines: Linking metabolic syndrome, the immune system, and arthritic diseases.

Metabolic syndrome (MetS) represents a cluster of metabolic and cardiovascular complications, including obesity and visceral adiposity, insulin resistance, dyslipidemia, hyperglycemia and hypertension, which directly increase the risk of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM2). Patients with arthritic diseases, such as rheumatoid arthritis and osteoarthritis, have a higher incidence of CVD. Although recent advances in the treatment of arthritic diseases, the incidence of CVD remains elevated, and MetS has been identified as a possible link between CVD and arthritic diseases.

Obesity, Fat Mass and Immune System: Role for Leptin.

Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism.

Inflammatory myopathy in the context of an unusual overlapping laminopathy.

Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery-Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot-Marie-Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported.

E74-Like Factor (ELF3) and Leptin, a Novel Loop Between Obesity and Inflammation Perpetuating a Pro-Catabolic State in Cartilage.

Background/aims: The E74-like factor 3 (ELF3) is an inflammatory mediator that participates in cartilage destruction in osteoarthritis. Leptin and other adipokines negatively impact articular cartilage, triggering catabolic and inflammatory responses in chondrocytes. Here, we investigated whether leptin induces ELF3 expression in chondrocytes and the signaling pathway involved in this process.

Adipokines and inflammation: is it a question of weight?

Obesity has reached epidemic proportions in the Western society and is increasing in the developing world. It is considered as one of the major contributors to the global burden of disability and chronic diseases, including autoimmune, inflammatory and degenerative diseases. Research conducted on obesity and its complications over the last two decades has transformed the outdated concept of white adipose tissue (WAT) merely serving as an energy depot.

Biomechanics, obesity, and osteoarthritis. The role of adipokines: When the levee breaks.

Osteoarthritis is a high-incidence painful and debilitating disease characterized by progressive degeneration of articular joints, which indicates a breakdown in joint homeostasis favoring catabolic processes. Biomechanical loading, associated with inflammatory and metabolic imbalances of joint, strongly contributes to the initiation and progression of the disease. Obesity is a primary risk factor for disease onset, and mechanical factors increased the risk for disease progression.

Progranulin as a biomarker and potential therapeutic agent.

Progranulin is a cysteine-rich secreted protein with diverse pleiotropic actions and participates in several processes, such as inflammation or tumorigenesis. Progranulin was first identified as a growth factor and, recently, it was characterised as an adipokine implicated in obesity, insulin resistance and rheumatic disease. At a central level, progranulin acts as a neurotropic and neuroprotective factor and protects from neural degeneration.

Leptin in the interplay of inflammation, metabolism and immune system disorders.

Leptin is one of the most relevant factors secreted by adipose tissue and the forerunner of a class of molecules collectively called adipokines. Initially discovered in 1994, its crucial role as a central regulator in energy homeostasis has been largely described during the past 20 years. Once secreted into the circulation, leptin reaches the central and peripheral nervous systems and acts by binding and activating the long form of leptin receptor (LEPR), regulating appetite and food intake, bone mass, basal metabolism, reproductive function and insulin secretion, among other processes.

Adipokines induce pro-inflammatory factors in activated Cd4+ T cells from osteoarthritis patient.

Osteoarthritis (OA) is a chronic systemic musculoskeletal disorder involving inflammation, immunity, and metabolic alterations. OA is commonly regarded as non-inflammatory disease; still inflammation is recognized as contributing to the symptoms and progression of OA. New evidence suggests that adipokines are involved in the pathophysiology of OA and might modulate the production of inflammatory mediators including in immune cells.

Pollutants make rheumatic diseases worse: Facts on polychlorinated biphenyls (PCBs) exposure and rheumatic diseases.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in adipose tissue, disturbing its metabolism and the balance of adipokines, related to obesity. The altering secretion pattern of adipokines from the adipose tissue and the increasing mechanical load in weight-bearing joints presented in obesity condition, are risk factors for osteoarthritis development. The most prevalent rheumatic diseases, osteoarthritis and rheumatoid arthritis, are chronic conditions that target the whole joints, leading to increasing disability and health care cost.

Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis.

Objective: To identify predictors of response to tumor necrosis factor (TNF) antagonists in ankylosing spondylitis (AS) and psoriatic arthritis (PsA).

Methods: Systematic review and meta-analysis of clinical trials and observational studies based on a systematic search. Meta-analyses of similar observations were performed using random effects computing summary OR.

Tocilizumab in giant cell arteritis: Multicenter open-label study of 22 patients.

Objective: To assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids.

Methods: A retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose.