Larry W Moreland's research while affiliated with University of Colorado and other places

Publications (429)

Article
With the arrival of biologics and the shift toward treat-to-target therapy, the possibility of a sustained clinical response has become an achievable goal for many patients with rheumatoid arthritis (RA). Although biologics have revolutionized the treatment of RA, they are costly, potentially inconvenient, and carry risks of side effects. Whether t...
Article
Objectives ANCA-associated vasculitis (AAV) is a group of multisystem diseases that can have several ocular manifestations. There are published data on ocular manifestations of granulomatosis with polyangiitis (GPA), but few for eosinophilic granulomatosis with polyangiitis (EGPA) or microscopic polyangiitis (MPA). There is little information conce...
Article
Full-text available
Objective To assess markers of neutrophil activation such as calprotectin and N-formyl methionine (fMET) in anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) and large-vessel vasculitis (LVV). Methods Levels of fMET, and calprotectin, were measured in the plasma of healthy controls (n=30) and patients with AAV (granulomatosis wi...
Article
Biologics are effective, though costly, medications for the treatment of rheumatoid arthritis (RA). Biosimilars are medications that have no clinically meaningful differences when compared with their corresponding reference biologics but cost significantly less. The U.S. Food and Drug Administration and the European Medication Agency have approved...
Article
Background Patient-based registries can help advance research on rare diseases such as eosinophilic granulomatosis with polyangiitis (EGPA), a complex multiorgan form of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Objective The aim of this study is to compare patient-reported and physician-reported data on manifestations, tre...
Article
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and inflammation. The finding of autoantibodies in seropositive RA suggests that complement system activation might play a pathophysiologic role due to the local presence of immune complexes in the joints. Our first objective was to explore the Pathobiology of...
Article
The etiology of rheumatoid arthritis (RA) is unknown. Previous studies of mouse models of RA have strongly implicated the alternative and lectin pathways of the complement system in disease pathogenesis. Here we explored the Pathobiology of Early Arthritis Cohort (PEAC) tissue RNA sequencing (RNA-seq) database and identify correlations among comple...
Preprint
Rheumatoid arthritis (RA) is a prototypical autoimmune disease that causes destructive tissue inflammation in joints and elsewhere. Clinical challenges in RA include the empirical selection of drugs to treat patients, inadequate responders with incomplete disease remission, and lack of a cure. We profiled the full spectrum of cells in inflamed syno...
Article
Objective To study the prevalence, risk and clinical associations of hypothyroidism among several forms of vasculitis. Methods Patients with giant cell arteritis (GCA), Takayasu arteritis (TAK), polyarteritis nodosa (PAN), and the three forms of ANCA-associated vasculitis (AAV, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA)...
Article
Background Rheumatoid arthritis (RA) is independently associated with an increased risk of cardiovascular disease (CVD). One of the early stages of atherosclerosis is endothelial dysfunction, which is increased in RA. Using drugs to target endothelial dysfunction is a promising novel strategy for CVD prevention in RA. Sildenafil has been shown to i...
Article
Full-text available
Objective To describe clinical manifestations and outcomes in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in North America. Methods Analysis of patients aged 18 years or older who fulfilled the 1990 American College of Rheumatology Classification Criteria for EGPA enrolled in the Vasculitis Clinical Research Consortium from...
Article
Full-text available
Currently, it remains difficult to identify which SNPs identified by GWAS are functional, and how various functional SNPs (fSNPs) interact and contribute to disease susceptibility. GWAS have identified a CD40 locus that is associated with rheumatoid arthritis (RA). We previously used two techniques developed in our lab, SNP-seq and FREP-MS, to dete...
Preprint
BACKGROUND Patient-based registries can help advance research in rare diseases such as eosinophilic granulomatosis with polyangiitis (EGPA), a complex, multi-organ form of anti-cytoplasm neutrophil antibody (ANCA)-associated vasculitis. OBJECTIVE To compare patient-reported vs. physician-reported manifestations, treatments, and outcomes for patien...
Article
Full-text available
Rheumatoid arthritis (RA) is a systemic and incurable autoimmune disease characterized by chronic inflammation in synovial lining of joints. To identify the signaling pathways involved in RA, its disease activity, and treatment response, we adapted a systems immunology approach to simultaneously quantify 42 signaling nodes in 21 immune cell subsets...
Article
Full-text available
Previously, using FREP-MS, we identified a protein complex including eight proteins that specifically bind to the functional SNP (fSNP) rs6032664 at a CD40 locus associated with autoimmune diseases. Among these eight proteins, four are ribosomal proteins RPL26, RPL4, RPL8, and RPS9 that normally make up the ribosomal subunits involved in the cellul...
Article
Objective To improve pneumococcal vaccination (PV) rates among rheumatology clinic patients on immunosuppressive therapy in the outpatient settings. Methods This quality improvement project was based on the pre-post-intervention design. Phase I of the project targeted rheumatoid arthritis patients from thirteen rheumatology clinics (1/2013 to 7/20...
Article
Objectives: Only a few small case series, case reports, and one small clinical trial suggested some benefit of leflunomide (LEF) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and other vasculitides. We analysed the clinical efficacy and tolerability of LEF in a large cohort of patients with various vasculitides. Methods: T...
Article
Objectives: Deficiency of adenosine deaminase 2 (DADA2) is a monogenic form of vasculitis that can resemble polyarteritis nodosa (PAN). This study screened for DADA2 in patients with presumed idiopathic PAN, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA) by DNA sequencing. Methods: Patients with idiopathic PAN (n=118)...
Article
Full-text available
Patients with rheumatoid arthritis (RA) are frequently treated with anti-TNFa immunoglobulin therapy but develop neutralizing antibodies against these drugs, necessitating therapeutic monitoring of drug concentrations and anti-drug antibodies. Patients with RA have multiple factors related to their autoimmune disposition that interfere with convent...
Article
Full-text available
Objectives Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. Methods Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospec...
Article
Background Takayasu’s arteritis (TAK) is a clinically heterogenous disease. Patterns of clinical presentation in TAK at diagnosis have not been well described, and a “triphasic pattern” of constitutional symptoms evolving into vascular inflammation and fibrosis has been reported but never systematically evaluated. Objectives To describe patterns o...
Article
Full-text available
Objective A Phase IV, open‐label, prospective study was conducted to characterize the long‐term safety of rituximab in a 4‐year observational registry of adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) within the United States. Methods Patients initiating treatment with rituximab were evaluated every 6...
Article
Objective Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular disease. Adventitial vasa vasorum density (aVVD), the vessel density of the vasa vasorum, is a surrogate measure for atherosclerotic plaque vulnerability. The purpose of this study was to compare the adventitial vasa vasorum density (aVVD) in RA and non-RA contr...
Article
Objectives: Takayasu's arteritis (TAK) is a clinically heterogenous disease. Patterns of clinical presentation in TAK at diagnosis have not been well described, and a “triphasic pattern” of constitutional symptoms evolving into vascular inflammation and fibrosis has been reported but never systematically evaluated. Methods: Patients with TAK were p...
Article
Full-text available
Rheumatoid arthritis (RA) is characterized by the production of anti-citrullinated protein antibodies (ACPAs). To gain insights into the relationship between ACPA-expressing B cells in peripheral blood (PB) and synovial tissue (ST), we sequenced the B cell repertoire in paired PB and ST samples from five individuals with established, ACPA+ RA. Bioi...
Article
Full-text available
We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture...
Article
Objectives: To develop and replicate, using data-driven methods, a novel classification system in Takayasu's arteritis based on distribution of arterial lesions. Methods: Patients were included from four international cohorts at major academic centres: India (Christian Medical College Vellore); North America (National Institutes of Health, Vascu...
Article
Objective We evaluated potential circulating biomarkers of disease activity in giant cell arteritis (GCA), Takayasu’s arteritis (TAK), polyarteritis nodosa (PAN), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss). Methods A panel of 22 serum proteins was tested in patients enrolled in the Vasculitis Clinical Research Consorti...
Article
Objective: To identify and validate, using computer-driven methods, patterns of arterial disease in Takayasu's arteritis (TAK) and giant cell arteritis (GCA). Methods: Patients with TAK or GCA were studied from the Diagnostic and Classification Criteria for Vasculitis (DCVAS) cohort and a combined North American (NA) cohort. Case inclusion requi...
Preprint
Full-text available
Rheumatoid arthritis (RA), a chronic autoimmune disease characterized by circulating autoantibodies, involves many cytokine-mediated signaling pathways in multiple immune cell subsets. Most studies of immune cells in RA have limitations, such as analysis of a small number of cell subsets or pathways, and limited longitudinal data on patient phenoty...
Article
Full-text available
To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an i...
Article
Objectives: To describe tracheobronchial disease in patients with granulomatosis with polyangiitis (GPA) and evaluate the utility of dynamic expiratory CT to detect large-airway disease. Methods: Demographic and clinical features associated with the presence of subglottic stenosis (SGS) or endobronchial involvement were assessed in a multicentre...
Article
Purpose of review: Uncertainty persists about the contribution of lipids to the increased risk of cardiovascular disease (CVD) among rheumatoid arthritis and other inflammatory joint disease (IJD) patients. In reviewing recent research, we consider potential insights gained by quantifying lipoprotein particles directly, rather than by their lipid...
Article
Full-text available
Objective The Patient Reported Outcome Measurement Information System (PROMIS) is a collection of item banks of self-reported health. This study assessed the feasibility and construct validity of using PROMIS instruments in vasculitis. Methods Data from a multicenter longitudinal cohort of subjects with systemic vasculitis were used. Instruments f...
Article
Objectives: The pathogenesis of eosinophilic granulomatosis with polyangiitis (EGPA) remains poorly understood, and may overlap with eosinophilic asthma and primary hypereosinophilic syndrome (HES). The aim of this study was to analyse a panel of serum cytokines and chemokines as markers of disease activity in patients with these conditions. Meth...
Article
Background: Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare a...
Article
Full-text available
Objective: Identification of a biomarker for disease activity in eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss) remains an unmet need. This study examined the value of serum periostin, a marker of type 2 inflammation, as a measure of disease activity in patients with EGPA. Methods: Participants enrolled in a multicenter, pro...
Article
Objective To determine contraception use among a cohort of reproductive‐age women (18‐50 years) with rheumatic diseases. Methods We conducted a study of administrative data from a single, large medical center between years 2013 and 2014. Women who had 1 of 21 rheumatic disease diagnoses and had at least 2 outpatient rheumatology visits were includ...
Article
Full-text available
Background: Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensio...
Preprint
Full-text available
To define the cell populations in rheumatoid arthritis (RA) driving joint inflammation, we applied single-cell RNA-seq (scRNA-seq), mass cytometry, bulk RNA-seq, and flow cytometry to sorted T cells, B cells, monocytes, and fibroblasts from 51 synovial tissue RA and osteoarthritis (OA) patient samples. Utilizing an integrated computational strategy...
Article
Background: The aims of this study were to define changes in catastrophizing that occur with initiation of a new disease-modifying antirheumatic drug (DMARD) and to examine the relationship between changes in Clinical Disease Activity Index (CDAI) and changes in catastrophizing. Methods: Participants in an ongoing multisite, prospective observat...
Article
Objective The Patient Reported Outcomes Measurement Information System (PROMIS) is a calibrated item bank used to assess patient reported outcomes across multiple domains. The purpose of this study was to describe the performance of selected PROMIS measures in rheumatoid arthritis (RA) patients with active disease, initiating a disease‐modifying an...
Article
Cardiovascular disease (CVD) risk is 1.5-fold higher in rheumatoid arthritis (RA), partly due to subclinical atherosclerosis that develops before the diagnosis of RA. Dyslipidemia in RA is better quantified by lipoproteins and apolipoproteins than by cholesterol levels. Current risk factors likely underestimate CVD risk by underestimating prior ris...
Article
Objectives: To evaluate large-vessel (LV) abnormalities on serial imaging in patients with giant cell arteritis (GCA) and discern predictors of new lesions. Methods: Clinical and imaging data from patients with GCA (including subjects diagnosed by LV imaging) enrolled in a prospective, multicenter, longitudinal study and/or a randomized clinical...
Article
Introduction The Outcome Measures in Rheumatology (OMERACT) ‘3x3′ method analyzes the occurrence of benefit and harm simultaneously at the individual patient level. We applied this method to two recent rheumatoid arthritis (RA) trial datasets. Methods Treatment of Early Aggressive RA (TEAR) and the RA Comparison of Active Therapies (RACAT) randomi...
Preprint
Background Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership (AMP) RA/SLE network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dime...
Article
Objectives: To evaluate damage and variables associated with damage in GCA. Methods: Patients with GCA enrolled in a prospective, multicentre, longitudinal study were included. Per-protocol assessments were made with the Vasculitis Damage Index and the Large-Vessel Vasculitis Index of Damage. Results: The study included 204 patients: 156 women...
Article
Background: Interleukin(IL)-13-producing CD8+ T cells have been implicated in the pathogenesis of type-2 driven inflammatory human conditions. We have shown that CD8+IL-13+ cells play a critical role in cutaneous fibrosis, the most characteristic feature of systemic sclerosis (scleroderma; SSc). However, the molecular mechanisms underlying IL-13 a...
Conference Paper
Background Therapy-related serious adverse events (SAEs) are important causes of morbidity in patients with GPA or MPA. Long-term safety data of rituximab in GPA/MPA are limited. Objectives To characterize safety events in an observational registry of patients with GPA/MPA initiating rituximab. Methods This interim analysis of RaVeR, an ongoing o...
Data
Supplementary Table 1. Sequences of primer pairs used in quantitative PCR analyses. Supplementary Table 2. Sequences of 20mer peptides used to evaluate T cell responses. Supplementary Table 3. Summary of patient demographics, clinical data and quality controls outcomes by cohort Supplementary Table 4. Results of genome‐wide association analysis for...
Data
Supplementary Figure 1. Quality Control and Study Design. AAV = ANCA‐associated vasculitis; GERA = Genetic Epidemiology Research on Aging; VCRC = Vasculitis Clinical Research Consortium; WGGER = Wegener's Granulomatosis Genetic Repository; UNC = University of North Carolina. Panel A shows the outcomes of genotyping quality control for single nucleo...
Article
Specific human leukocyte antigen (HLA)-DRB1 alleles encode a "shared epitope" (SE) associated with rheumatoid arthritis (RA), especially more severe cyclic-citrullinated peptide antibody-positive (anti-CCP+) RA. Associations of SE alleles (0, 1 or 2) with total and cardiovascular disease (CVD) mortality and incident coronary heart disease (CHD), CV...
Article
Objective: Pain sensitization may contribute to pain severity in rheumatoid arthritis (RA), impacting assessment of disease activity. We examined whether pain processing mechanisms were associated with disease activity among RA patients with active disease. Methods: This study includes 139 subjects enrolled in the Central Pain in Rheumatoid Arth...
Article
Full-text available
Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main diseas...
Article
Full-text available
Objectives: To determine the prevalence of anti-myeloperoxidase (MPO) antibodies of IgA (IgA anti-MPO) isotype in patients with eosinophilic granulomatosis with polyangiitis (EGPA), and the association of the IgA antibodies with IgG anti-MPO and with disease activity. Methods: Serum samples from patients with EGPA followed in a multi-center long...
Article
Full-text available
Background The target sample size for clinical trials often necessitates a multicenter (center of excellence, CoE) approach with associated added complexity, cost, and regulatory requirements. Alternative recruitment strategies need to be tested against this standard model. Objectives The aim of our study was to test whether a Web-based direct rec...
Article
Evidence suggests the greater than 1.5 increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) is related to an accelerated burden of subclinical atherosclerosis that develops before the diagnosis of RA. Dyslipidemia in RA is better quantified by lipoproteins and apolipoproteins than cholesterol levels. Current risk factors like...
Article
Objective: To compare the efficacy of abatacept to placebo for giant cell arteritis (GCA). Methods: In this multicenter trial, patients with newly-diagnosed or relapsing GCA were treated with abatacept 10 mg/kg IV on days 1, 15, 29, week 8, together with prednisone. At week 12, patients in remission underwent a double-blinded randomization to co...
Article
Objective: To compare the efficacy of abatacept to placebo for the treatment of Takayasu's arteritis (TAK). Methods: In this multicenter trial, patients with newly-diagnosed or relapsing TAK were treated with abatacept 10 mg/kg IV on days 1, 15, 29, week 8, together with prednisone. At week 12, patients in remission underwent a double-blinded ra...
Article
Objective: In RA, autoreactive B cells are pathogenic drivers and sources of anti-citrullinated protein antibodies (ACPA) that serve as a diagnostic biomarker and predictor of worse long-term prognosis. Yet the immunobiologic significance of persistent ACPA production at a cellular level is poorly understood. Methods: In a cross-sectional study...
Article
Full-text available
Th17 and TfH cells are thought to promote tissue inflammation and autoantibody production, respectively, in autoimmune diseases including rheumatoid arthritis (RA). TfH cells that co-express Th17 markers (CXCR5+Th17) encompass both of these pathogenic functions, and are increased in some human autoimmune settings including juvenile dermatomyositis....
Article
Full-text available
Objective: To identify risk alleles relevant to the cause and biology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: We conducted a genome-wide association and subsequent replication study including 1986 cases of AAV [granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)] and 4723 controls...
Article
Objective. To improve herpes zoster (HZ) vaccination rates in high-risk patients with rheumatoid arthritis (RA) being treated with immunosuppressive therapy. Methods. This quality improvement project was based on the pre- and post-intervention design. The project targeted all patients with RA over the age of 60 years while being treated with immun...
Article
Full-text available
Nature Communications 7 : Article number: 12460 10.1038/ncomms12460 ( 2016 ); Published: 23 August 2016 ; Updated: 10 October 2016 . The HTML version of this Article incorrectly duplicated the authors S.
Data
Supplementary Figures 1-6, Supplementary Tables 1-4, Supplementary Note 1 and Supplementary References
Article
Full-text available
Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment eff...
Article
Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment eff...
Article
Objective: Abnormal function of high density lipoprotein (HDL) has been implicated as a potential mechanism for the increased cardiovascular disease (CVD) in patients with rheumatoid arthritis. The current work evaluated changes in HDL function and HDL-associated proteins over two years of follow-up in early RA patients receiving either methotrexa...
Article
Full-text available
Background The aim was to compare the effect of etanercept (ETN) and conventional synthetic disease-modifying anti-rheumatic drug (DMARD) therapy on serum amyloid A (SAA) levels and to determine whether SAA reflects rheumatoid arthritis (RA) disease activity better than C-reactive protein (CRP). Methods We measured SAA and CRP at baseline, 24, 48,...
Article
Th17 and TfH cells are thought to promote tissue inflammation (Th17) and autoantibody production (TfH) in rheumatoid arthritis (RA) and other autoimmune diseases. TfH cells that co-express Th17 markers (Th17/TfH) correlate with disease activity in juvenile dermatomyositis. However, Th17/TfH cells have not been detailed in RA subjects in context of...
Article
Objectives: To evaluate the cost-effectiveness of all 4 interventions in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) clinical trial: Immediate triple (IT), immediate etanercept (IE), step-up triple (ST), and step-up etanercept (SE). Step-up interventions started methotrexate and added either etanercept or sulfasalazine plus hydro...
Article
Full-text available
Background: There is abundant evidence that low socioeconomic status (SES) is associated with worse health outcomes among people with Rheumatoid Arthritis (RA); however, the influence of socioeconomic disadvantage in early life has yet to be studied within that population. Methods: Data originated from the cross-sectional arm of the Consortium E...
Article
Full-text available
Background: There is abundant evidence that low socioeconomic status (SES) is associated with worse health outcomes among people with Rheumatoid Arthritis (RA); however, the influence of socioeconomic disadvantage in early life has yet to be studied within that population. Methods: Data originated from the cross-sectional arm of the Consortium Eval...