Paul Monach

Boston University | BU · Department of Medicine

Levels of neutrophil extracellular traps (NETs) were measured in plasma of healthy controls (HC, n = 30) and patients with granulomatosis with polyangiitis (GPA, n = 123), microscopic polyangiitis (MPA, n = 61), Takayasu's arteritis (TAK, n = 58), and giant cell arteritis (GCA, n = 68), at times of remission or activity and correlated with levels o...

Objective: Vitamin D might participate in the pathogenesis of several immune-mediated diseases, but few related data are available for ANCA-associated vasculitis (AAV). In this study, we analysed the association between vitamin D status and disease in patients with AAV. Methods: Serum levels of 25(OH)D2/ 3 were measured in 125 randomly selected...

Objectives Severe infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial. Methods Data on 197 patients recruited...

Objective Proteinase 3 (PR3) is the major antigen for anti-neutrophil cytoplasmic antibodies (ANCAs) in the systemic autoimmune vasculitis, granulomatosis with polyangiitis (GPA). PR3 anti-neutrophil cytoplasmic antibodies (PR3-ANCAs) recognize different epitopes on PR3. We aimed to study the effect of mutations on PR3 antigenicity. Methods The re...

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...

Objective: Autoreactive B cells are responsible for ANCA production in ANCA-associated vasculitis (AAV). Rituximab depletes circulating B cells including autoreactive ones. We aimed to evaluate changes and associations with relapse of the circulating autoreactive B cell pool following therapeutic B cell depletion in AAV. Methods: Sequential flow...

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...

Background The frequency of the proteinase 3 gene (PRTN3) polymorphisms in patients with ANCA-associated vasculitis (AAV) is not well characterized. We hypothesize that PRTN3 gene polymorphisms induce allosteric changes in PR3 conformation which may alter its interaction with ligands and PR3-ANCA during inflammation with potential implications for...

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...

Objective Improved biomarkers of current disease activity and prediction of relapse are needed in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). For clinical relevance, biomarkers must perform well longitudinally in patients on treatment and in patients with nonsevere flares. Methods Twenty-two proteins were measured in 347 serum...

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)...

Background: Little is known about the autoreactive B cells in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3 (PR3+) B cells. Methods: Multicolor flow cytometry in combination with bioinformatics and functional in vitro studies wer...

To better define the control of immune system regulation, we generated an atlas of microRNA (miRNA) expression from 63 mouse immune cell populations and connected these signatures with assay for transposase-accessible chromatin using sequencing (ATAC–seq), chromatin immunoprecipitation followed by sequencing (ChIP–seq) and nascent RNA profiles to e...

Neutrophils are implicated in multiple homeostatic and pathological processes, but whether functional diversity requires discrete neutrophil subsets is not known. Here, we apply single-cell RNA sequencing to neutrophils from normal and inflamed mouse tissues. Whereas conventional clustering yields multiple alternative organizational structures, dif...

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...

(1) describe imaging features of CIA, (2) compare dilation rate and wall thickening of aortic aneurysms in patients with CIA versus those with giant cell arteritis/aortitis (GCA), (3) present clinical outcomes of CIA patients. Retrospective search of electronic records from 2004 to 2018 yielded 71 patients, 52 of whom were female, with a mean age o...

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...

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr...

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...

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)...

Background: The utility of ANCA testing as an indicator of disease activity in ANCA-associated vasculitis (AAV) remains controversial. This study aimed to determine the association of ANCA testing by various methods and subsequent remission and examine the utility of a widely used automated addressable laser-bead immunoassay (ALBIA) to predict dise...

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...

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...

Background Proteinase 3 (PR3)-reactive B cells are present in PR3-ANCA-associated vasculitis (AAV) at levels higher than healthy controls. Objectives To evaluate the dynamics of the PR3-reactive B cell repopulation in patients with PR3-AAV after treatment with rituximab, and to analyze possible associations between these immunological changes and...

Background Bartonellosis is an emerging anthropozoonosis caused by infection with intracellular Gram-negative Bartonella species. It leads to necrotizing granulomas and endothelial damage and causes acute and chronic human diseases, such as cat scratch disease, bacillary angiomatosis and endocarditis. Endocarditis due to Bartonella henselae and B....

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...

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...

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...

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...

CD4 effector lymphocytes (T ) are traditionally classified by the cytokines they produce. To determine the states that T cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic T cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing...

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...

Objective: To investigate serum IL-6 (sIL-6) levels during active disease, complete remission (CR), and relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to explore the association of changes in sIL-6 with clinical outcomes. Methods: sIL-6 levels were measured at baseline and longitudinally over 18 months, in...

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...

Objective Patients with ANCA‐associated vasculitis (AAV) are at elevated risk for cardiovascular disease (CVD). A clearer understanding of the association between changes in disease activity and lipid levels in AAV would inform CVD risk stratification in this population. Methods Lipid levels were assessed using baseline and month 6 stored serum sa...

Background We recently reported that, in a small number of subjects, the proportion of proteinase 3 (PR3)-specific B cells was higher in patients with PR3-ANCA-associated vasculitis (AAV) compared to healthy controls (HCs). Objectives The objectives of this work were to replicate our previous findings on a larger number of subjects, including myel...

Objectives: We aimed to assess the frequency of venous thromboembolic events (VTEs) observed in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial and identify novel potential risk factors. Methods: VTEs in 197 patients enrolled in the RAVE trial were analysed. Baseline demographics, univariate and multivariate analyses were performed to i...

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...

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...

Objective Proteinase 3 (PR3) is the major antigen for anti-neutrophil cytoplasmic antibodies (ANCAs) in the systemic autoimmune vasculitis, granulomatosis with polyangiitis (GPA). PR3 anti-neutrophil cytoplasmic antibodies (PR3-ANCAs) recognize different epitopes on PR3. We aimed to study the effect of mutations on PR3 antigenicity. Methods The re...

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...

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...

Glucocorticoids are standard of care for many chronic inflammatory conditions, including juvenile dermatomyositis (JDM) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We sought to define pharmacodynamic biomarkers of therapeutic efficacy and safety concerns of glucocorticoid treatment for these two disorders. Previous...

Objective This study examined the association between Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms and granulomatosis with polyangiitis (GPA), and MIF's role in a murine model of granulomatous vasculitis. Methods The human study involved 1077 patients with GPA and controls. Genotyping for the MIF ‐794 CATT5‐8 promoter micros...

Background The deregulated overproduction of interleukin (IL)−6 has been implicated in several inflammatory and antibody-mediated autoimmune diseases. Objectives To investigate serum IL-6 levels (sIL-6) during active disease, remission, and relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to explore the associ...

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...

Objectives To evaluate circulating cytokine profiles in patients with ANCA‐associated vasculitis (AAV), classified by ANCA specificity (proteinase 3 (PR3)‐ANCA versus myeloperoxidase (MPO)‐ANCA) or by clinical diagnosis (granulomatosis with polyangiitis (GPA) versus microscopic polyangiitis (MPA)). Methods A panel of 29 cytokines was tested in 186...

Background and objectives: The significance of persistent hematuria or proteinuria in patients with ANCA-associated vasculitis who are otherwise in clinical remission is unclear. Design, setting, participants, & measurements: A post hoc analysis was conducted using participants enrolled in two randomized, placebo-controlled clinical trials who h...

Objectives: To study the determinants of the pharmacokinetics (PK) of rituximab (RTX) in patients with ANCA-associated vasculitis (AAV) and its association with clinical outcomes. Methods: This study included data from 89 patients from the RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375 mg/m2). RTX was quantified...

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...

Background: Immunopathologic features predict renal function at baseline and follow-up in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN). The interstitial infiltrate consists predominantly of T lymphocytes, but their pathophysiologic significance is unclear, especially in light of the success of B-cell-directed thera...

Background Evidence supporting the classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) based on ANCA type is accumulating.¹ Objectives To evaluate serum cytokine profiles in patients with AAV classified by ANCA specificity (proteinase 3 (PR3)-ANCA versus myeloperoxidase (MPO)-ANCA) or by clinical diagnosis (...

Background Response to rituximab (RTX) is variable in patients with ANCA-associated vasculitis (AAV), and predictors of treatment efficacy/relapse risk would be useful. Previous studies have shown that RTX pharmacokinetics (PK) is associated with treatment efficacy in patients with lymphoma. Objectives To study the determinants of RTX PK in patien...

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...

Background Eosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti–interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis. Methods In this multicenter, double-blind, parallel-group, phase 3 trial, we randomly a...

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...

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...

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...

18th International Vasculitis and ANCA Workshop, Univ Tokyo, Tokyo, JAPAN, MAR 25-28, 2017

A 57-year-old woman presented with fatigue, night sweats, weight loss, headache, abdominal pain, and skin lesions. Laboratory testing revealed hypergammaglobulinemia and hypocomplementemia. Diagnostic tests were performed.

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...

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...

Antineutrophil cytoplasmic antibodies (ANCA) appear to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). Yet, ANCA alone are not sufficient to generate disease, and some evidence suggests that infectious triggers may serve as inciting events for AAV disease activity. Antibodies of the IgM isotype often serve as markers...

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 c...

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...

Objective: We investigated the relationships between glucocorticoid use, disease activity, and changes in body mass index (BMI) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: We analyzed AAV patients enrolled in the Rituximab in AAV trial. Glucocorticoid use, BMI, and disease activity were measured reg...

Objective: To examine the relationship of antineutrophil cytoplasmic antibody (ANCA) type and ANCA-associated vasculitis (AAV) diagnosis with demographic features, disease manifestations, and clinical outcomes. We focused on patients who account for the differences between ANCA type and disease type classifications: anti-myeloperoxidase (MPO)-ANCA...

Objectives: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in AAV. This study investigated serum S100A8/A9 levels as a biomarker predicting future relapse in a large cohort of patients with severe ANCA-associated vasculitis (AAV). Methods: Serum levels of S100A8/A9 were measured at baseline, months 2, and 6 foll...