To explore incidence and progression of coronary atherosclerosis and identify determinants in patients with rheumatoid arthritis (RA). We specifically evaluated the impact of inflammation, cardiac risk factors, duration of medication exposure, and their interactions on coronary plaque progression.

Massive weight loss leads to marked knee pain reduction in individuals with knee pain, but the reason for the reduction in pain is unknown. This study was undertaken to quantify the contribution of magnetic resonance imaging (MRI)–evidenced changes in pain‐sensitive structures, bone marrow lesions (BMLs), and synovitis, and changes in pain sensitization or depressive symptoms, to knee pain improvement after substantial weight loss.

Ankylosing spondylitis (AS) is an inflammatory arthritis in which men have a higher risk of developing progressive axial disease than women. Transcriptomic studies have shown reduced expression of cytotoxic cell genes in the blood of AS patients. HLA–B27 contributes the greatest risk for AS, suggesting a role for CD8+ T cells. This study was undertaken to profile AS patient cytotoxic cells with the hypothesis that an alteration in CD8+ T cells might explain the aberrant cytotoxic profile observed in patients.

Alterations of the gut microbiota have been implicated in many forms of arthritis, but an examination of cartilage microbial patterns have not been performed. The objective of this study was to characterize the microbial DNA profile of articular cartilage and determine changes associated with osteoarthritis (OA).

Plasmablasts play important roles in autoimmune diseases, including systemic lupus erythematosus (SLE). Activation of mechanistic target of rapamycin complex 1 (mTORC1) is regulated by amino acid levels. In patients with SLE, mTORC1 is activated in B cells and modulates plasmablast differentiation. However, the detailed mechanisms of amino acid metabolism in plasmablast differentiation remain elusive. Here, we evaluated the effects of methionine in human B cells.

We would like to thank Dr. Park and colleagues for their interest in our manuscript on lupus psychosis and for their description of Four Cases of Lupus Associated Psychosis. Albeit rare in occurrence, psychosis has been reported as an early manifestation of SLE in several studies. In the SLICC cohort the earliest psychotic episode occurred 2 months prior to the diagnosis of SLE and so it is incorrect that “almost a quarter occurred a year prior to the diagnosis of lupus”.

To investigate effect of therapies on radiographic progression in axial spondyloarthritis (axSpA).

We read with great interest the paper by Hanly et al (1) discussing lupus‐associated psychosis. The authors present data from the largest prospective inception cohort study to date (Systemic Lupus International Collaborating Clinics (SLICC) Cohort), which demonstrate that psychosis is a relatively rare event, occurring in 1.53% of all NPSLE patients. Of these patients with lupus‐associated psychosis, almost a quarter occurred a year prior to the diagnosis of lupus, and over 80% resolved within a year. While this might suggest a benign course for psychosis, each episode of psychosis is a severe organ threatening manifestation of SLE and should be treated with immunosuppressant medications.

A 39‐years‐old woman, was diagnosed with limited pulmonary granulomatosis with polyangiitis (GPA) five years ago.

Select biosimilars—versions of originator biologic drugs made by different manufacturers—have provided substantial cost savings in some European countries.(1) For example, Denmark obtained a 64% discount in a mandatory nationwide non‐medical switch from originator to biosimilar infliximab.(2) In the US, for systemic inflammatory conditions such as rheumatoid arthritis, five originator tumor necrosis factor (TNF) inhibitors—adalimumab (Humira), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade)—and two infliximab biosimilars—infliximab‐dyyb (Inflectra, approved in April 2016, marketed in November 2016) and infliximab‐abda (Renflexis, approved in April 2017, marketed in July 2017)—are currently available.

To address whether a targeted modulation of the abnormal expression of heat shock protein (HSP)70 and autoantibodies against this molecule in systemic lupus erythematosus (SLE) can influence disease.

Fc receptors for IgGs (FcγRs) play important roles both in protective and pathogenic immune responses. The assembly of the CARD9/BCL10/MALT1 signalosome is required for optimal FcγR‐induced canonical NF‐κB activation and pro‐inflammatory cytokine release. Our goal was to clarify the relevance of the MALT1 protease activity in FcγR‐driven events and the therapeutic potential of selective MALT1 protease inhibitors in FcγR‐mediated diseases.

GWASs have identified many susceptibility loci for systemic lupus erythematosus (SLE). However, most of these loci are located in noncoding regions of the genome. Long noncoding RNAs (lncRNAs) are pervasively expressed and reported to be involved in various diseases. This study aimed to explore the genetic significance of lncRNAs in SLE.

Rising US drug expenditures are driven primarily by spending on specialty biologic drugs. From 2014 to 2018 alone, spending on biologic drugs increased 50% to $125 billion (1). Growing spending reflects rising biologic drug prices, not just increased use. Many policy analysts, including the Congressional Budget Office (CBO), forecasted that biosimilars would curb spending by finally introducing competition into the marketplace.

In 2016, the American Academy of Ophthalmology (AAO) changed the recommended daily dose of hydroxychloroquine (HCQ) from 6.5 mg/kg to <5 mg/kg. However, it is not clear that the lower prescribed dose of HCQ will have the same efficacy for systemic lupus erythematosus (SLE) activity or the same role in protecting against cardiovascular risk factors and thrombosis. This study was undertaken to address the frequency of HCQ retinopathy and the role of HCQ blood levels in identifying those individuals who are at a greater future risk of retinopathy.

To develop an evidence‐based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.

Billions of public dollars are spent each year on biologic disease‐modifying antirheumatic drugs (DMARDs), but the drivers of recent increases in biologic DMARD spending are unclear. This study was undertaken to characterize changes in total spending and unit prices for biologic DMARDs in Medicare and Medicaid programs and quantified the major sources of these spending increases.

Pain sensitization contributes to the complex osteoarthritis (OA) pain experience. The relation between hand OA imaging features and clinically assessed pain sensitization is largely unexplored. We aimed to examine the association of structural and inflammatory features of hand OA with local pressure pain thresholds in the Nor‐Hand study.

Systemic juvenile idiopathic arthritis (JIA) is a form of arthritis in childhood that is initially dominated by innate immunity–driven systemic inflammation and is thus considered a polygenic autoinflammatory disease. However, systemic JIA can progress toward an adaptive immunity–driven afebrile arthritis. Based on this observation of biphasic disease progression, a “window of opportunity” for optimal, individualized and target‐directed treatment has been proposed. This hypothesis requires testing, and in this review we summarize current evidence regarding molecular factors that may contribute to the progression from an initially predominantly autoinflammatory disease phenotype to autoimmune arthritis. We consider the involvement of innately adaptive γδ T cells and natural killer T cells that express γδ or αβ T cell receptors but cannot be classified as either purely innate or adaptive cells, versus classic B and T lymphocytes in this continuum. Finally, we discuss our understanding of how and why some primarily autoinflammatory conditions can progress toward autoimmune‐mediated disorders over the disease course while others do not and how this knowledge may be used to offer individualized treatment.

Neutrophils are key immune cells participating in host defense through several mechanisms, including the formation of neutrophil extracellular traps (NETs). This study was undertaken to investigate the role of neutrophils in juvenile dermatomyositis (JDM).

Patients with hypomorphic mutations in DNase II develop a severe and debilitating autoinflammatory disease. This study was undertaken to compare the disease parameters in these patients to those in a murine model of DNase II deficiency, and to evaluate the role of specific nucleic acid sensors and identify the cell types responsible for driving the autoinflammatory response.

Autoantibodies against citrullinated proteins are found in 64–89% of rheumatoid arthritis (RA) patients, with 88–99% specificity. This study was undertaken to create an unbiased, comprehensive profile of serum antibodies against the human proteome, including the citrullinome and the homocitrullinome, in RA patients, using a high‐density peptide array.

To determine whether systemic lupus erythematosus (SLE) can develop in the absence of BAFF in an SLE‐prone host.

To evaluate patterns of elevations of isotypes of rheumatoid factor (RF) and anti–citrullinated protein antibodies (ACPAs) pre–rheumatoid arthritis (RA) diagnosis and post–RA diagnosis.

To assess the benefit of the recombinant human interleukin‐1 receptor antagonist anakinra in treating pediatric patients with secondary hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) associated with rheumatic and nonrheumatic conditions.

To examine changes in the extent of specific patterns of interstitial lung disease (ILD) as they transition from one pattern to another in response to immunosuppressive therapy in systemic sclerosis–related ILD (SSc‐ILD).

To determine the stage of B cell development at which a systemic lupus erythematosus (SLE)–associated DNA methylation signature originates in African American (AA) and European American (EA) subjects, and to assess whether epigenetic defects in B cell development patterns could be predictive of SLE status in individual and mixed immune cell populations.

Monocular cell infiltration and type I IFN system activation play an important role in primary Sjögren’s syndrome (pSS). This study aimed to clarify the mechanism of Poly (ADP‐Ribose) Polymerase Family Member 9 (PARP9) on monocular cell infiltration triggered by type I IFN.

To address the independent role of peptidylarginine deiminase type 2 and 4 (PAD2 and PAD4, respectively) in generating rheumatoid arthritis (RA) autoantigens by using a system that mimics intracellular citrullination in the RA joint.

With great interest, we read the commentary by Dr. Ryu Watanabe. This commentary highlights the main findings of our recent study that demonstrates the biased mal‐differentiation of Th1 and Th17 cells in patients with Takayasu's arteritis (TAK) and identifies mTORC1 hyperactivity as the T cell‐intrinsic mechanism [1]. Accordingly, targeting mTORC1 efficiently abrogates the pro‐inflammatory T cell differentiation and ameliorates arterial inflammation in humanized TAK model [1].

Rheumatoid arthritis (RA) risk is strongly influenced by environmental exposures and the organ with the largest interface with our environment is the lung. To effectively exchange oxygen for carbon dioxide, the lung must support a delicately thin mucosal border (2 µm) spread over 140 m2 (1). While ideal for gas exchange, the immensity of the lung’s surface area makes it challenging to mitigate threats from inhaled pathogens and toxins while simultaneously promoting immunologic tolerance to harmless epitopes. A failure to maintain homeostatic host‐environment interactions along this mucosal border is implicated in the pathogenesis of many lung diseases and growing evidence suggests it is also implicated in the pathogenesis of RA.

I read the article by Zhang et al. published in this journal with great interest (1). They demonstrated that CD4+ T cells isolated from Takayasu's arteritis (TAK) are biased to differentiate into Th1 and Th17 cells because of mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity. Subsequently, using human artery‐NSG chimera model, they showed that mTORC1 inhibition, by either rapamycin or RNAi technology, effectively abrogated the mal‐differentiation of TAK CD4+ T cells and vascular inflammation.

This study aimed to investigate the role of an inflammatory lipid mediator, leukotriene B4 (LTB4), and its receptor BLT1 in systemic sclerosis (SSc).

To determine the 5‐year outcome of treatment for meniscal tear in osteoarthritis.

Familial hemophagocytic lymphohistiocytosis (FHLH) is a complex cytokine storm syndrome caused by genetic abnormalities rendering CD8+ T cells and natural killer cells incapable of cytolytic killing. In murine models of FHLH, interferon‐γ (IFNγ) produced by CD8+ T cells has been identified as a critical mediator of disease, and an IFNγ‐blocking antibody (emapalumab) has recently been approved by the Food and Drug Administration. However, development of hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in patients who are genetically unresponsive to IFNγ questions the absolute necessity of IFNγ in driving disease. This study was undertaken to determine the necessity of IFNγ in driving HLH.

Takayasu arteritis (TAK) is a progressive autoimmune large vessel vasculitis with infiltration of proinflammatory T cells, with a largely unknown etiology. This study was undertaken to explore the involvement of mechanistic target of rapamycin (mTOR) in proinflammatory T cell differentiation and disease progression in TAK.

To investigate a role for insulin‐resistant pathways in inflammation and therapeutic targeting for disease modification in Rheumatoid Arthritis.

Peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients exhibit a gene expression program (interferon [IFN] signature) that is attributed to overproduction of type I IFNs by plasmacytoid dendritic cells. Type I IFNs have been thought to play a role in the pathogenesis of SLE. This study was undertaken to examine an unexpected influence of monocyte/macrophages on the IFN signature.

Few studies have systematically and quantitatively addressed the impact of urate‐lowering therapy on monosodium urate (MSU) deposits. This study was undertaken to analyze the effect of lifestyle measures and conventional urate‐lowering therapy on MSU deposits in patients with gout.

T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).

Anti–citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are commonly present in rheumatoid arthritis (RA) without a clear rationale for their coexistence. Moreover, autoantibodies develop against proteins with different posttranslational modifications and native proteins without obvious unifying characteristics of the antigens. We undertook this study to broadly evaluate autoantibody binding in seronegative and seropositive RA to identify novel features of reactivity.

Rheumatoid arthritis (RA) is preceded by autoantibodies to citrullinated proteins (ACPA). Citrullins are arginine residues which have been modified by Peptidyl Arginyl Deiminases (PADs). PAD4 is the target of autoantibodies in RA. This suggests that ACPAs could arise because PAD4 is recognized by T cells which help the production of autoantibodies to proteins bound by PAD4. We previously found evidence for this hapten carrier model in mice. Here, we looked for evidence for this model in humans.

Genetic variants in the region of TNFAIP3 interacting protein 1 (TNIP1) are associated with autoimmune disease and reduced TNIP1 gene expression. This study aimed to define the functional genetic mechanisms driving TNIP1 hypomorphic expression imparted by the SLE‐associated TNIP1 H1 risk haplotype.

Type I interferon (IFN‐I) responses are broadly associated with autoimmune disease including SLE. Given the cardinal role of autoantibodies in SLE, we investigated whether a B cell‐specific IFN assay might correlate with SLE activity.

To assess the impact of knee chondrocalcinosis (CC) on the 5‐year risk of joint replacement and disease progression in patients with knee osteoarthritis (KOA).

To examine modifiable risk factors in relation to the presence of hyperuricemia and to estimate the proportion of hyperuricemia cases in the general population that could be prevented by risk factor modification, along with estimates of the variance explained.

Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are linked to inflammation and autoimmunity, including rheumatoid arthritis (RA). However, whether NETs are present in the circulation of RA patients and contribute to inflammation and disease progression has not been carefully addressed. We undertook this study to assess markers of neutrophil activation and NET formation in plasma samples, investigating whether they add clinical value in improving the determination of prognosis and monitoring in RA patients.

IgG4‐related disease (IgG4‐RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4‐RD.

IgG4‐related disease (IgG4‐RD) is a unique inflammatory disorder in which Th2 cytokines promote IgG4 production. In addition, recent studies have implicated the Toll‐like receptor (TLR) pathway. This study was undertaken to examine the expression of TLRs in salivary glands (SGs) from patients with IgG4‐RD.

To evaluate the antiinflammatory and analgesic effects of sepiapterin reductase (SPR) inhibition in a mouse model of inflammatory joint disease, and to determine whether urinary sepiapterin levels, as measured in mice and healthy human volunteers, could be useful as a noninvasive, translational biomarker of SPR inhibition/target engagement.

To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients.

To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis (RA).

We previously reported that the co‐activation of NF‐κB and STAT3 in non‐immune cells including synovial fibroblasts enhances the expression of NF‐κB target genes, playing a role in chronic inflammation including rheumatoid arthritis (RA). Here we examined the role of NF‐κB activation in chondrocytes to understand the pathogenesis of RA. Furthermore, we investigated TMEM147 as a representative NF‐κB activator in chondrocytes.

Knee cartilage damage is often linked to mechanical overloading. However, cartilage requires mechanical load to remain healthy, suggesting that underloading may be detrimental. We examined knee overloading and underloading by defining cumulative load as the joint effects of body mass index (BMI) and daily walking, and examined the relation of cumulative load to worsening cartilage damage over two years.

While biologic therapies have dramatically improved the management of rheumatoid arthritis (RA), not all patients respond well to treatment and the field continues to await individualized medicine approaches that promise to determine effective medications based on a patient’s distinct disease features. The cellular and molecular characterization of an individual’s synovium holds promise to understand pathology, predict outcomes and tailor treatment decisions, akin to the histologic and genetic assessment of tumor tissue that guides cancer care.

A 55‐year‐old woman presented with a ten‐year history of progressive deformities of her hands and feet. She had been diagnosed with systemic lupus erythematosus (SLE) ten years previously, with high anti‐nuclear antibody (ANA) titers, low complement levels, oral ulceration, arthritis, and left leg deep vein thrombosis. She did not adhere to treatment and only took low‐dose prednisone and warfarin intermittently.

Rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) exhibit alterations in brain connectivity synonymous with central sensitization. This study was undertaken to investigate how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with FM.

Systemic lupus erythematosus (SLE) patients exhibit accelerated development of atherosclerosis and increased incidents of cardiovascular disease (CVD) that cannot be explained by traditional risk factors alone. Accumulating evidence suggests that reduced levels of high‐density lipoproteins (HDLs), along with altered HDL composition and function, may contribute to the accelerated atherosclerosis in SLE patients. Normally, HDLs play various atheroprotective roles through facilitating cholesterol efflux, inhibiting vascular inflammation, and scavenging oxidative species. However, systemic inflammation, oxidative stress, and autoimmunity in SLE patients induce changes in HDL size distribution and proteomic and lipidomic signatures. These compositional changes in HDLs result in the formation of proinflammatory, dysfunctional HDL. These lupus‐altered HDLs have impaired antiatherogenic function with reduced cholesterol efflux capacities, impaired antioxidation abilities, and diminished antiinflammatory properties. In fact, dysfunctional HDL may promote atherogenesis by inducing inflammation. Thus, dysfunctional HDLs could be an important biomarker of accelerated atherosclerosis in lupus. Additionally, HDL‐targeted therapies, especially infusion of reconstituted HDLs, may serve as a potential therapeutic intervention for SLE patients with CVD.

Autoantibodies targeting histidyl–transfer RNA synthetase (HisRS; anti–Jo‐1) are common in the idiopathic inflammatory myopathies (IIMs) and antisynthetase syndrome. This study was undertaken to investigate immunity against HisRS in the blood and lungs of patients with IIM/antisynthetase syndrome.

Evaluate the efficacy and safety of ustekinumab through 1 year in a phase II Systemic Lupus Erythematosus (SLE) trial.