Recent progress in the treatment of lupus nephritis.

The treatment of lupus nephritis has seen significant advances during the past decade mainly due to the publication of well-designed randomized clinical trials (RCTs). The choice of treatment is guided by the histopathologic classification but is also influenced by demographic, clinical, and laboratory characteristics that allow for the identification of patients at risk for more aggressive disease. For the induction arm, low-dose cyclophosphamide regimens and mycophenolate mofetil have been validated as alternatives to the established National Institutes of Health regimen of high-dose cyclophosphamide; for the maintenance phase, azathioprine and mycophenolate compete for treatment of first choice.

Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease.

There is a need in autoimmune diseases to uncover the mechanisms involved in the natural resolution of inflammation. In this article, we demonstrate that granulocytic myeloid-derived suppressor cells (G-MDSCs) abundantly accumulate within the peripheral lymphoid compartments and target organs of mice with experimental autoimmune encephalomyelitis prior to disease remission. In vivo transfer of G-MDSCs ameliorated experimental autoimmune encephalomyelitis, significantly decreased demyelination, and delayed disease onset through inhibition of encephalitogenic Th1 and Th17 immune responses.

Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout.

Background: Gout is a prevalent inflammatory arthritis affecting 1-2% of adults characterized by activation of innate immune cells by monosodium urate (MSU) crystals resulting in the secretion of interleukin-1β (IL-1β). Since neutrophils play a major role in gout we sought to determine whether their activation may involve the formation of proinflammatory neutrophil extracellular traps (NETs) in relation to autophagy and IL-1β.

Methodology/principal Findings: Synovial fluid neutrophils from six patients with gout crisis and peripheral blood neutrophils from six patients with acute gout and six control subjects were isolated.

Balancing efficacy and toxicity of novel therapies in systemic lupus erythematosus.

Therapy of systemic lupus erythematosus has been facing the paradox of an overwhelming rate of trials testing novel potential therapeutic agents and the lack of US FDA approval of a single new drug for over five decades. Heterogeneity in disease phenotype, concomitant immunosuppressive medication and a lack of unequivocal hard end points for clinical trials have proven to be significant obstacles in establishing efficacy of candidate therapies. Nevertheless, combination regimens with already existing agents have shown efficacy with acceptable safety profiles, mainly in cases of refractory to conventional treatment disease.

TRAF1/C5, eNOS, C1q, but not STAT4 and PTPN22 gene polymorphisms are associated with genetic susceptibility to systemic lupus erythematosus in Turkey.

A significant source of variability in the literature on systemic lupus erythematosus (SLE) susceptibility genes has been the inability to replicate genetic findings across different racial or ethnic groups. We investigated whether a single nucleotide polymorphism (SNP) of the STAT4 (rs7574865), PTPN22 (rs2476601), TRAF1/C5 (rs10818488), and C1q (rs292001) genes as well as the 27-bp VNTR polymorphism on intron 4 of eNOS, previously associated with SLE in other populations, are also associated with SLE risk in Turkey. A group of 158 SLE patients and 155 healthy controls were included in this study.

European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies.

Background: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD).

A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression: implications for the pathogenesis.

Background: In systemic lupus erythematosus (SLE) sustained CD40L expression by T cells and platelets activates a variety of cells via its receptor CD40 contributing to disease pathogenesis. Although CD40 has recently been identified in genome-wide association study as a novel rheumatoid arthritis susceptibility gene such an association has not been documented for SLE.

Objective: To investigate whether the rs4810485 CD40 single nucleotide polymorphism (SNP) is associated with increased risk for SLE and its impact on CD40 expression.

Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression.

Objective: MicroRNAs (miRNAs) regulate the expression of genes involved in immune activation. A study was undertaken to characterise the miRNA signature and identify novel genes involved in the regulation of immune responses in systemic lupus erythematosus (SLE).

Methods: The expression of 365 miRNAs in peripheral blood mononuclear cells of patients with SLE and healthy controls was analysed using TaqMan Low Density Arrays.

Association of the PTPN22 R620W polymorphism with increased risk for SLE in the genetically homogeneous population of Crete.

Autoimmune diseases affect approximately 5% of the population, but much work remains to define the genetic risk factors and pathogenic mechanisms underlying these conditions. There is accumulating evidence that common genetic factors might predispose to multiple autoimmune disorders. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune disorders with multiple susceptibility genes.

Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative.

Objective: A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties.

Methods: An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires).

Air trapping in Wegener's granulomatosis: an additional finding on expiratory chest HRCT.

Purpose: This study was undertaken to assess the presence and extent of air trapping (AT) on high-resolution computed tomography (HRCT) in patients with Wegener's granulomatosis (WG) and to correlate the finding with the inspiratory pattern and bronchial/bronchiolar involvement.

Materials And Methods: Twenty-one patients (7 M/14 F) with WG underwent inspiratory and expiratory HRCT. Images were evaluated for the presence and extent of AT and for airway involvement (bronchi/bronchioles); the predominant HRCT pattern was also documented.

Podocyte main slit diaphragm proteins, nephrin and podocin, are affected at early stages of lupus nephritis and correlate with disease histology.

Renal podocytes and their slit diaphragms ensure the integrity of the renal basement membrane that forms the barrier to urinary protein loss. A putative disruption of the slit diaphragm and its main protein components, nephrin and podocin, may be implicated in the pathogenesis of lupus nephritis (LN). We studied the glomerular protein expression of nephrin and podocin in NZB/W LN mice by Western blot and immunofluorescence; mRNA levels were measured by real-time PCR.

The negative costimulatory molecule PD-1 modulates the balance between immunity and tolerance via miR-21.

Disruption of the programmed death-1 (PD-1) pathway leads to breakdown of peripheral tolerance and initiation of autoimmunity. The molecular pathways that mediate this effect remain largely unknown. We report here that PD-1 knockout (PD-1(-/-) ) mice develop more severe and sustained Ag-induced arthritis (AIA) than WT animals, which is associated with increased T-cell proliferation and elevated levels of IFN-γ and IL-17 secretion.

The development of a simple questionnaire to screen patients with SLE for the presence of neuropsychiatric symptoms in routine clinical practice.

Aim: The creation of a physician-administered questionnaire to screen patients with Systemic Lupus Erythematosus (SLE) for the presence of symptoms suggestive of neuropsychiatric involvement (NPSLE).

Methods: The development of the questionnaire followed three phases. First, a list of manifestations was prepared based on the ACR case definitions for NPSLE.

Development of quality indicators to evaluate the monitoring of SLE patients in routine clinical practice.

The assessment of systemic lupus erythematosus (SLE) patients in routine clinical practice is mainly based on the experience of the treating physician. This carries the risk of unwanted variability. Variability may have an impact on the quality of care offered to SLE patients, thereby affecting outcomes.

Does rituximab increase the incidence of infectious complications? A narrative review.

Background: Rituximab has increasingly been used for the treatment of hematological malignancies and autoimmune diseases, and its efficacy and safety are well established. Although clinical trials have shown conflicting results regarding the association of rituximab with infections, an increased incidence of infections has recently been reported in patients with lymphomas being treated with rituximab. However, clinical experience regarding the association of rituximab with different types of infection is lacking and this association has not been established in patients with rheumatoid arthritis.

Gene network analysis of bone marrow mononuclear cells reveals activation of multiple kinase pathways in human systemic lupus erythematosus.

Background: Gene profiling studies provide important information for key molecules relevant to a disease but are less informative of protein-protein interactions, post-translational modifications and regulation by targeted subcellular localization. Integration of genomic data and construction of functional gene networks may provide additional insights into complex diseases such as systemic lupus erythematosus (SLE).

Methodology/principal Findings: We analyzed gene expression microarray data of bone marrow mononuclear cells (BMMCs) from 20 SLE patients (11 with active disease) and 10 controls.

The role of the pro-apoptotic protein Siva in the pathogenesis of Familial Mediterranean fever: A structural and functional analysis.

Familial Mediterranean fever (FMF) is an autosomal, recessive disease, attributed to mutations in MEFV gene encoding pyrin, which is characterized by recurrent, acute and self-limiting attacks of fever as well as an increased neutrophil and monocyte apoptosis. Most disease-associated mutations in MEFV gene reside on the C-terminal PRYSPRY (B30.2) domain of pyrin, an area found to interact with the pro-apoptotic protein Siva.

EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs.

Objectives: To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.

Methods: The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.

Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade.

Immune responses against endogenous nuclear antigens are characteristic of systemic lupus erythematosus (SLE), a highly pleiomorphic disease predominantly affecting young women of reproductive age. Genome-wide association studies have confirmed the importance of genes associated with the immune response as well as genes involved in endothelial function and tissue response to injury. Immune complexes, autoantibodies, complement, cytokines, endothelial injury and a thrombophilic state associated with antiphospholipid antibodies are important for mediating tissue dysfunction.

Innate immunity in systemic lupus erythematosus: sensing endogenous nucleic acids.

Historically, the involvement of complement - an integral part of the innate immune response- in the pathogenesis of lupus was recognized early. Emphasis shifted quickly however to the specific immunity with scientists concentrating on the adaptive immune response (autoantigens, autoreactive T cells and autoantibodies). Similarly, the detection of interferon alpha (IFNα), another key mediator of innate immunity, in the sera of active lupus patients by Hooks and Moutsopoulos in 1979 was poorly understood and thus ignored for many years.