Marvin Fritzler

University of Calgary · Faculty of Medicine

Objectives Antiphospholipid syndrome (APS) is characterised by the presence of antiphospholipid antibodies (aPLs) and clinical outcomes of thrombosis and/or obstetric morbidity and is associated with systemic lupus erythematosus (SLE). IgG antiphosphatidylserine/prothrombin complex (aPS/PT), IgM aPS/PT and IgG anti-beta 2 glycoprotein 1-domain 1 (a...

Introduction Despite progress in our understanding of disease pathogenesis for systemic autoimmune rheumatic diseases (SARD), these diseases are still associated with high morbidity, disability, and mortality. Much of the strongest evidence to date implicating environmental factors in the development of autoimmunity has been based on well-establish...

br> Aim: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microsc...

This pilot randomized controlled trial assessed the immunogenicity of paediatric vs adult hepatitis A vaccine doses in immunosuppressed adolescents (12–15 years) with juvenile idiopathic arthritis and Crohn’s disease. The study aimed to assess if a single, higher dose provides better immunogenicity, particularly before travel.

Background Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. Met...

Artificial intelligence and machine learning applications are emerging as transformative technologies in medicine. With greater access to a diverse range of big datasets, researchers are turning to these powerful techniques for data analysis. Machine learning can reveal patterns and interactions between variables in large and complex datasets more...

Objectives The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis patients. The aim of this study was to compare phenotypic features of anti-U1RNP+ mixed connective t...

Introduction Scurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the Foxp3 gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies...

Introduction Cytokines are mediators of the immune system that are essential for the maintenance, development and resolution of immune responses. Beneficial immune responses depend on complex, interdependent networks of signaling and regulatory events in which individual cytokines influence the production and release of others. Since disruptions in...

Purpose of review This manuscript reviews recently published advances in the identification of autoimmune inflammatory myopathies (AIM)-specific and AIM-related autoantibodies considered of value in the workup of patients suspected of having AIM. Newer autoantibodies, developments, and advances in the methodology of testing, the gaps and pitfalls i...

Diagnosis of autoimmune diseases is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the conditions. This review focused on the current knowledge of the role of autoantibodies' testing in various diseases, such as systemic lupus erythematosus, rheumat...

The kinesin superfamily protein 20B (KIF20B), also known as M-phase phosphoprotein-1, is a plus-end-directed motor enzyme for cytokinesis. Anti-KIF20B antibodies have been reported in idiopathic ataxia, but no previous studies have examined anti-KIF20B antibodies in systemic autoimmune rheumatic diseases (SARDs). We aimed to establish methods for d...

Exploration of cytokine levels in systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is needed to find common and diverse biomolecular pathways. Circulating levels of 87 cytokines were compared amongst 19 healthy controls and consecutive patients with SSc-ILD (n = 39), SSc without ILD (n = 29),...

Objectives A novel longitudinal clustering technique was applied to comprehensive autoantibody data from a large, well-characterised, multinational inception systemic lupus erythematosus (SLE) cohort to determine profiles predictive of clinical outcomes. Methods Demographic, clinical and serological data from 805 patients with SLE obtained within...

Objectives: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, mic...

Anti-nuclear (ANA) are present in approximately 90% of systemic sclerosis (SSc) patients and are key biomarkers in supporting the diagnosis and determining the prognosis of this disease. In addition to the classification criteria autoantibodies for SSc [i.e., anti-centromere, anti-topoisomerase I (Scl-70), anti-RNA polymerase III], other autoantibo...

Background The significance of antiphospholipid antibodies (aPL) in COVID-19 remains uncertain. Objective We determined if aPL were associated with COVID-19, and/or thrombosis or adverse outcomes during COVID-19 hospitalization. Methods Symptomatic adults tested for SARS-CoV-2 for clinical reasons (March-July 2020) with either ≥1 PCR positive (CO...

Background Increased autoantibody prevalence has been described in instances of high-dose exposure to polychlorinated biphenyls (PCBs). In 1996, an equipment malfunction at the Swan Hills Treatment Centre in Alberta, Canada, caused the release of gases containing PCBs into the ambient air. In view of the immune effects of PCBs and their potential a...

(1) Background: Myositis specific antibodies (MSA) are important diagnostic biomarkers. Among the rarest and most challenging MSA are anti-OJ antibodies which are associated with anti-synthetase syndrome (ASS). In contrast to the other tRNA synthetases that are targets of ASS autoantibodies (e.g Jo-1, PL-7, PL-12, EJ, KS, Zo), OJ represents a macro...

The objective of this study is to report the clinical, serological and pathological features of patients with autoimmune myositis other than dermatomyositis, who displayed both muscle weakness on physical examination and prominent B cell aggregates on muscle pathology, defined as ≥ 30 CD20+ cells/aggregate. Specifically, the presence of a brachio-c...

Objective: The rationale for this study was based on reports that valosin-containing protein (VCP) mutations are found in hereditary inclusion body myositis (IBM) and VCP was detected in rimmed vacuoles of sporadic IBM (sIBM) muscle biopsies. Autoantibodies to VCP have not been reported in sIBM or other inflammatory myopathies (IIMs). The aim of t...

Objectives: Cognitive dysfunction (CD) is a common manifestation of systemic lupus erythematosus (SLE) which can have detrimental consequences for those affected. To date, no treatments have been approved for SLE- CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medicatio...

Objectives The development of autoantibody directed towards citrullinated proteins (ACPA) are predictive of RA in at-risk individuals. The biological events that underpin loss of immune tolerance and progression into inflammatory arthritis are not known. We sought to identify serum proteomic alterations that drive autoantibody formation, persistenc...

Objectives To determine if serologic phenotypes could be identified in systemic lupus erythematosus patients developing interstitial lung disease (ILD) and/or myositis. Methods Adult SLE patients (without myositis/ILD at baseline) had annual assessments and serum sampling between 2000 and 2017. New-onset ILD was identified using the SDI pulmonary...

Autoimmune cholestatic liver disease includes both Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). Both conditions result in impairment of hepatic bile flow ultimately leading to chronic liver injury, liver fibrosis and eventually end stage cirrhosis. Early and accurate diagnosis are important for the risk stratification...

Aims: To perform ultrastructural and histopathological analysis of muscle biopsies from a large group of systemic sclerosis (SSc) patients, including some with early/mild SSc features, and examine whether capillary pathology differentiates 'scleromyositis' (SM) from other auto-immune myositis (AIM) subsets. Methods: Muscle biopsies from a total...

Anti-Ki/SL antibodies were first described in 1981 and have been associated with systemic lupus erythematosus (SLE) and Sicca syndrome. Despite the long history, very little is known about this autoantibody system, and significant confusion persists. Anti-Ki/SL antibodies target a 32 kDa protein (also known as PSME3, HEL-S-283, PA28ƴ, REGƴ, proteas...

Objective: Cognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood-brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we deter...

Objective: The study objective was to identify differences in gene expression between treatment responders (TRs) and treatment non-responders (TNRs) diagnosed with juvenile dermatomyositis (JDM). Methods: Gene expression analyses were performed using whole blood messenger RNA sequencing in patients with JDM (n = 17) and healthy controls (HCs; n...

Background Antinuclear Antibodies (ANA) detected in juvenile idiopathic arthritis (JIA) sera are considered to be a biomarker for JIA-related uveitis. There is an unclear consensus on the screening dilutions of ANA as detected by the HEp-2 indirect immunofluorescence assay (IFA) that should be used when predicting the risk of uveitis in JIA. The pr...

Cytokine autoantibodies, particularly those directed to type I interferon (T1IFN), have been reported to portend an increased risk of severe COVID-19. Since SLE is one of the conditions historically associated with T1IFN autoantibodies, we sought to determine the prevalence of cytokine autoantibodies in our local cohort of 173 patients with SLE pre...

Objectives A perception derived from cross-sectional studies of small systemic lupus erythematosus (SLE) cohorts is that there is a marked discrepancy between antinuclear antibody (ANA) assays, which impacts on clinicians’ approach to diagnosis and follow-up. We compared three ANA assays in a longitudinal analysis of a large international incident...

Dear Editor, with interest, we read the recent article by He et al. [1] comparing line immunoassay (LIA) for the detection of myositis specific antibodies (MSA) with the HEp-2 indirect immunofluorescence assay (IFA) in a ‘real-world’ cohort of patients investigated for idiopathic inflammatory myopathies (IIM). We thank the authors for sharing their...

Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defin...

Background Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE) characterized by decreased lung volumes and diaphragmatic weakness in a dyspneic patient. Chest wall dysfunction secondary to pleuritis is the most commonly proposed cause. In this case report, we highlight a new potential mechanism of SLS in SLE,...

COVID‐19 (SARS‐CoV‐2 infection) can lead to intensive care unit (ICU) admission and critical illness myopathy (CIM). We examined three ICU patients with COVID‐19, who required mechanical ventilation for pneumonia and developed CIM. Pathological examination of skeletal muscle biopsies revealed myopathic changes consistent with CIM, variable inflamma...

Objective: The objective of this study was to assess the predictive significance of anti-Scl-70 (anti-topoisomerase I) antibodies, as determined by three different methods, for decline in forced vital capacity (FVC) within the first year of follow-up in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD). Methods: Pati...

The classification and diagnosis of systemic autoimmune diseases are frequently based on a collection of criteria composed of clinical, laboratory, imaging, and pathology elements that are strongly associated with the respective disease. Autoantibodies are a distinctive hallmark and have a prominent position in the classification criteria of many a...

Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are reported in systemic sclerosis (SSc) but its involvement in SSc pathogenesis is not clear. In the present study we assessed markers of neutrophil activation and NET formation in SSc patients in relation to markers of inflammation and disease phenotype. Fact...

The establishment of the International Consensus on ANA Patterns (ICAP) in 2014-2015 was welcomed by members of the medical community as a significant improvement in guiding harmonization of ANA test interpretation and reporting. In the subsequent years, several itinerant meetings and continuous interaction with the community contributed to dissemi...

Objective To examine associations between sunlight exposure and anti–citrullinated protein antibodies (ACPAs) using general population data in Quebec, Canada. Methods A random sample of 7,600 individuals (including 786 subjects who were ACPA positive and 201 self‐reported rheumatoid arthritis [RA] cases) from the CARTaGENE cohort was studied cross...

Objective We previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM’s concurrent criter...

Background To evaluate the interpretation and reporting of antinuclear antibodies (ANA) by indirect immunofluorescence assay (IFA) using HEp-2 substrates based on common practice and guidance by the International Consensus on ANA patterns (ICAP). Method Participants included two groups [16 clinical laboratories (CL) and 8 in vitro diagnostic manuf...

Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a standardized way, adding value to laboratory findings and helping with critical clinical decisions. This paper proposes a test report based on the practices informed by 118 laborator...

The relation between infections and autoimmune diseases has been extensively investigated. Multiple studies suggest a causal relation between these two entities with molecular mimicry, hyperstimulation and dysregulation of the immune system as plausible mechanisms. The recent pandemic with a new virus, i.e., SARS-CoV-2, has resulted in numerous stu...

Introduction Antiphospholipid syndrome (APS) is an autoimmune condition characterized by the presence of antiphospholipid antibodies (aPL) and clinical outcomes of thrombosis and obstetric morbidity. APS is more common in patients with systemic lupus erythematous (SLE), with persistently positive aPLs being found in 20-30% of SLE patients. The revi...

Background Cognitive impairment (CI) in SLE is highly prevalent. Several factors are associated with CI: depression, pain, fatigue, medications, as well as more specific SLE factors such as disease damage, and autoantibodies. We aimed to phenotype CI in SLE using machine learning techniques to enable personalised targeted treatments. Methods SLE p...

Background Prior studies of SLE clusters based on autoantibodies have utilized cross-sectional data from single centers. We applied clustering techniques to longitudinal and comprehensive autoantibody data from a large multinational, multi-ethnic inception cohort of well characterized SLE patients to identify clusters associated with disease outcom...

Immune checkpoint inhibitors (ICI) have dramatically improved the treatment of certain types of cancer and represent an example of applied precision medicine (PM). However, some patients treated with ICI can develop immune-related adverse events (irAE) that can progress to overt life-threatening diseases. During the past years, there have been a fl...

Objective A close temporal relationship between systemic sclerosis (SSc) onset and cancer has been reported in anti-RNA polymerase III-positive patients. We investigated the association between cancer and other SSc autoantibodies in a national SSc registry. Methods SSc patients enrolled in the Canadian Scleroderma Research Group registry from 2004...

Objective Dispersion, or variability in an individual’s performance across multiple tasks at a single assessment visit, has been associated with cognitive dysfunction (CD) in many neurodegenerative and neurodevelopmental disorders. We aimed to compute a dispersion score using neuropsychological battery (NB) tests and determine its association with...

Objective The aim of this study was to determine the independent value of N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein to predict onset of cardiopulmonary disease in a large, multi-center systemic sclerosis cohort followed prospectively. Methods Subjects from the Canadian Scleroderma Resear...

The body’s innate and acquired immune systems are critical in responses to a wide spectrum of assaults, including SARS-CoV-2 infection. We identify studies of autoimmunity to support our hypothesis that a high intelligence quotient (IQ) may put children at increased risk for severe COVID-19 sequelae; especially those whose viral load is high and/or...

Objectives: To examine i) the relationship between neuropsychological performance and depression and anxiety over time, and ii) the overlap between classification of cognitive dysfunction, anxiety, and depression in SLE. Methods: 301 patients with SLE were included. Cognition was measured using a modified version of the ACR neuropsychological ba...

High levels of anti-citrullinated protein antibodies (ACPA) are often observed prior to a diagnosis of rheumatoid arthritis (RA). We undertook a replication study to confirm CpG sites showing evidence of differential methylation in subjects positive vs. negative for ACPA, in a new subset of 112 individuals sampled from the population cohort and bio...

This chapter provides an overview of key autoantibodies used in the diagnosis and management of SLE. Issues addressed are the advantages to, but limitations of, ANA testing and what the key considerations are in ordering ANA tests and then interpreting the results. There is a progressive move toward closing the seronegative gap in SLE, the use of s...

Objective Scleromyositis remains incompletely characterized owing in part to its heterogeneity. The purpose of this study was to explore the role of autoantibody profiles to define subsets of scleromyositis. Methods Subjects with scleromyositis from a prospective cohort were divided into 3 groups based on autoantibody profiles: subjects with SSc-s...

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several anti-nuclear antibodies (ANA), including those in the classification criteria (anti-centromere, anti-topoisomerase I (Scl-70), anti-RNA Pol III). However, the presence of less common antibodies such as anti-fibrillarin (U3-RNP) that generate a clumpy nucleolar pa...

Objective To review: (1) degree of conformity to the American College of Rheumatology neuropsychological battery (ACR-NB) among studies that used a NB, (2) review definitions of cognitive impairment (CI) from studies that used a NB, and (3) characterize measurement tools used to assess CI in systemic lupus erythematosus (SLE). Methods The literatu...

Dating to the discovery of the Lupus Erythematosus (LE) cell in 1948, there has been a dramatic growth in the discovery of unique autoantibodies and their cognate targets, all of which has led to the availability and use of autoantibody testing for a broad spectrum of autoimmune diseases. Most studies of the sensitivity, specificity, commutability,...

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of life-threatening COVID-19 are believed to disproportionately affect certain at-risk populations. However, it is not clear whether individuals with cystic fibrosis (CF) are at a higher risk of COVID-19 or its adverse consequences. Recurrent respi...