Øyvind Molberg

• MD, PhD
• Professor (Full) at University of Oslo

Background Progression of interstitial lung disease (ILD) reduces long-term survival in patients with systemic sclerosis (SSc), such that aggressive treatment and tight monitoring should be considered in appropriate patients. Conversely, identifying stable SSc-ILD patients over time is important in clinical practice to avoid overtreatment and inclu...

Background Giant cell arteritis (GCA) is a chronic large-vessel vasculitis that affects mainly the aorta and its primary branches, and in Western countries is the most common form of vasculitis in people older than 50 years. The most severe manifestations of GCA include blindness and ischemic stroke caused by occlusion of affected arteries. GCA pre...

Background Lupus nephritis (LN) is one of the main clinical challenges in systemic lupus erythematosus (SLE) and a cause of significant morbidity and mortality. Genetic contribution to SLE pathogenesis is important, and genetic profiling through polygenic risk scores has been shown useful to stratify SLE patients according to dominating molecular d...

Background The IgG4-related disease (IgG4-RD) responder index (RI) is a validated tool to assess disease activity in IgG4-RD [1]. The RI reflects symptoms attributable to active IgG4-RD as well as relevant findings from the physical examination, imaging and laboratory evaluations, with higher scores reflecting more active disease. Multiorgan involv...

Background Connective tissue disease (CTD) is an umbrella term for a heterogeneous group of autoimmune diseases affecting the connective tissue in various organs. One of the most serious complications associated with CTDs is interstitial lung disease (ILD), which results in significant morbidity and mortality. A subset of CTD-ILD patients shows pro...

Background A subset of patients with connective tissue disease associated interstitial lung disease (CTD-ILD) progresses. These patients have been included in clinical ILD trials as a group despite their different underlying diseases. It has not been studied whether this basket approach of pooling different CTD-ILDs is valid, e.g., if the disease c...

Background Interstitial lung disease (ILD) progression can be assessed using different definitions. Declining forced vital capacity (FVC) is the simplest and most accepted. Both progressive pulmonary fibrosis (PPF) as defined by the 2022 ATS/ERS/JRS/ALAT guideline, and progressive fibrosing ILD (PF-ILD) as used in INBUILD, define progressive diseas...

Background Gastrointestinal dysmotility is a common complication in systemic sclerosis (Sc) patients including slow colonic transit leading to gastrointestinal tract (GIT) symptoms. Fecal microbiota transplantation (FMT) with ACHIM did not improve lower or total GIT symptoms in SSc patients compared to placebo enrolled in the Norwegian multicenter,...

Background Accurate estimations of incidence rates are important in all epidemiological studies. Register derived International Classification of Disease (ICD) codes appear near ideal case defining items being seemingly specific and easy to access in large populations, but their applicability in complex clinical syndromes like SLE is still unclear....

Background Interstitial lung disease (ILD) is a major cause of morbidity and mortality in systemic sclerosis (SSc). In clinical practice, physicians often wait for progression to initiate or escalate therapy. Similarly, progressive SSc-ILD patients are recruited into trials to enrich for further progression. These strategies assume that patients wi...

Background Systemic sclerosis (SSc) is a multi-organ disease and patient-reported outcome measures (PROMs) are important to better understand the complexity and impact of the disease. This heterogeneous disease has a wide specter of symptoms, and there are several different PROMs in use for this disease-group to assess all possible symptoms. Recent...

Background Cardiovascular morbidity, severe infection and renal damage are amongst the most serious complications of SLE. Objectives To combine a mendelian randomization (MR) approach and investigation of a clinical SLE cohort to evaluate the contribution of SLE-genetic risk to the development of myocardial infarction (MI), end-stage renal disease...

Background Progression of interstitial lung disease (ILD) is a candidate for long-term mortality in patients with systemic sclerosis (SSc). Different definitions of progression have been proposed. Declining lung function is often used, whereas others include composite definitions such as the 2022 ATS/ERS/JRS/ALAT guideline criteria for progressive...

Background Lower gastrointestinal tract (GIT) complications are common in patients with systemic sclerosis (SSc), associate with a high disease burden, and current treatment alternatives are limited. Patients with SSc have also an altered intestinal microbiota composition. This provides a rational for the investigation of fecal microbiota transplan...

Purpose Lupus nephritis (LN) is a major cause of morbidity in Systemic Lupus Erythematosus (SLE) and a subset of patients still develop end stage renal disease (ESRD). Genetics is important in SLE pathogenesis and today >180 SLE risk loci have been identified at Genome-wide significance (GWS). Here we investigate how gene-gene interactions influenc...

Purpose Norway is one of the few countries worldwide where societal factors facilitate complete population-based cohorts on rare diseases. Due to the organization of the specialist health services all patients with systemic lupus erythematosus (SLE) are likely to be captured at public hospitals. In addition, national identity numbers prevent lost t...

Purpose Lupus nephritis (LN) is a major clinical challenge and cause of significant morbidity and mortality in systemic lupus erythematosus (SLE). Today >180 SLE risk loci at Genome-wide significance (GWS, p < 5×10–8), including risk genes involved in B-cell function, have been identified. Associations between an individual’s genetical burden and c...

Background Systemic sclerosis (SSc) carries a high risk for progressive interstitial lung disease (ILD). Several anti-inflammatory therapies have been used to treat SSc-ILD and recently the first antifibrotic therapy has been approved. Personalized treatment strategies are largely missing to date. The two chemokines, CCL2 (MCP-1) and CCL17 (TARC),...

Background Milestones in the field of IgG4-related disease (IgG4-RD) include the 2011 Comprehensive Diagnostic Criteria (CDC) (1), the 2019 ACR/EULAR classification criteria (2), and the recent identification of four distinct clinical phenotypes (3). Performance of the criteria and phenotypic disease expression in Scandinavian populations are large...

Background Interstitial lung disease (ILD) in primary Sjögren’s syndrome (pSS) has been reported to be present in 10-15% of patients, but pSS-ILD behavior over time is not well characterized. Objectives Assess the pattern of ILD in pSS, its disease behavior and factors associated with disease progression in a well-characterized pSS-ILD cohort. Me...

Background Systemic sclerosis (SSc) is a complex autoimmune, multi-organ disease with gastro-intestinal tract (GIT) involvement significantly contributing to comorbidity. While understanding of mechanisms behind SSc-related GIT disease is incomplete, recent work shows that altered gut microbiota (dysbiosis) is present in many patients and associate...

Background Based on the argument that symptoms define disease, physicians commonly apply the terms “preclinical” or “subclinical” disease to describe patients with disease-related findings but no accompanying symptoms for connective tissue disease associated interstitial lung disease (CTD-ILD). The term subclinical frequently applies to patients wi...

Background Gastro-intestinal tract (GIT) symptoms is highly prevalent in patients with systemic sclerosis (SSc). The GIT-symptoms impact on the quality of life is significant, and available treatment alternatives are limited. Recently published articles show associations between gut microbiota changes and GIT-symptoms in SSc. We, therefore, perform...

Background Gastrointestinal tract (GIT) involvement is associated with high morbidity in systemic sclerosis (SSc) but the data on its impact from unselected and well characterized SSc cohorts are scarce. Currently, the effect of immunosuppressive (IS) treatment on GIT involvement is largely unknown. Objectives To evaluate the severity and worsenin...

Background Gastrointestinal tract (GIT) involvement is highly prevalent in systemic sclerosis (SSc) and associates with GIT symptoms that are present early and progress over time. Changes in gut microbiota are often reported in inflammatory disease settings but whether GIT symptoms associate with altered immune recognition of specific gut bacteria...

Background ASSD is characterized by antisynthetase antibodies (ARS) and the triad arthritis/myositis/Interstitial Lung Disease (ILD). ASSD and systemic sclerosis (SSc) may share features, like Raynaud’s phenomenon (RP), capillaroscopic alterations, and also some SSc specific autoantibodies. Objectives To evaluate the characteristics of ASSD + for...

Background In systemic sclerosis (SSc) patients with interstitial lung disease (ILD) approximately 30% show progressive ILD. It is unknown whether a progressive ILD period is followed by further lung function decline. In clinical practice, treatment is frequently initiated after observation of lung function decline over 6-12 months and lung functio...

Objective To perform a comprehensive evaluation of and identify correlates for physical fitness in consecutive patients with juvenile idiopathic arthritis (JIA) who have been diagnosed in the era of biologics and to compare the results with those obtained in healthy controls. Methods The study cohort included 60 patients with JIA (50 girls) ages 1...

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presen...

Rationale: Interstitial lung disease (ILD) represents a major challenge in systemic sclerosis (SSc), but there are no precise, population-based data on its overall impact, limiting opportunities for screening and management strategies. Objective: Evaluate impact of ILD in a unique, nationwide, population based SSc cohort. Methods: ILD was asse...

Background Systemic sclerosis (SSc) is a progressive, multi organ, auto-immune disease marked by frequent and severe gastrointestinal (GI) afflictions and gut dysbiosis. Objectives Determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in pat...

Background Interstitial lung disease (ILD) represents a clinical challenge in systemic sclerosis (SSc) and associates with high mortality. The presence of severe lung fibrosis is a strong predictor for early mortality. There is substantial progress in SSc-ILD research, but precise, population-based data on cumulative incidence, range of severity an...

Objective Primary cardiac involvement is presumed to account for a substantial part of disease‐related mortality in systemic sclerosis (SSc). Still, there are knowledge gaps on the evolution and total burden of systolic dysfunction in SSc. Here we evaluated prospective left ventricular (LV) and right ventricular (RV) systolic function in an unselec...

Objectives Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to...

Combining HLA-DQ–gluten tetramers with mass cytometry and RNA sequencing analysis, we find that gluten-specific CD4+ T cells in the blood and intestines of patients with celiac disease display a surprisingly rare phenotype. Cells with this phenotype are also elevated in patients with systemic sclerosis and systemic lupus erythematosus, suggesting a...

Objective Interstitial lung disease (ILD) in systemic sclerosis (SSc) runs a highly variable course, and prediction tools are highly desired. The aim of this study was to assess the diagnostic and prognostic performance of 4 candidate serum biomarkers for SSc‐associated ILD. Methods Serum samples from a combined cohort of SSc patients (from Paris,...

Cell subset driving celiac disease elevated in multiple autoimmune disorders. Combining HLA-Class II tetramers with CyTOF (mass cytometry) and RNA seq to study gluten-specific CD4+ T cells.

Background Even though progressive rhinosinusitis with osteitis is a major clinical problem in granulomatosis with polyangiitis (GPA), there are no studies on how GPA-related osteitis develops over time, and no quantitative methods for longitudinal assessment. Here, we aimed to identify simple and robust CT-based methods for capture and quantificat...

We thank Xu and co‐workers for their interest regarding our newly published article on the role of CCL21 in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc) (1). Here, we want to respond to their concerns. This article is protected by copyright. All rights reserved.

Background Dysregulation of Fractalkine (CX3CL1) and its receptor CX3CR1 has been linked to the pathobiology of chronic inflammatory conditions. We explored CX3CL1 in systemic sclerosis (SSc) related progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in two different but complementary sources of biomaterial. Methods We col...

Venn diagram for the primary ILD endpoint. Venn diagram including the frequency of events for each parameter included in the primary composite ILD outcome; with the blue circle showing the frequency of annual FVC decline >5%, the red circle showing the frequency of annual DLCO decline>7.5% and the green circle showing the frequency of the 1-year mo...

Anonymized data from the OUH cohort. Anonymized data file including clinical data and CX3CL1 levels SSc patients and healthy controls. (ZIP)

Anonymized data from the UCLA cohort. Anonymized data file including clinical data and CX3CL1 levels SSc patients and healthy controls. (ZIP)

Univariable logistic regression analyses of the composite ILD endpoint. Univariable logistic regression analyses of clinical characteristics and the composite ILD outcome measure in the Oslo University Hospital SSc cohort. (PDF)

We thank Zhou and co‐workers for their interest regarding our newly published manuscript on the role of CCL21 in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). Here, we want to respond to their concerns. Genome‐wide association studies (GWASs) have been foreshadowed to be a major advance in biomedical discovery, wit...

Objectives: Studies assessing relative mortality risks across the spectrum of systemic inflammatory rheumatic diseases are largely missing. In this study, we wanted to estimate standard mortality ratios (SMRs) and causes of death in an ethnically homogeneous cohort covering all major CTDs and primary systemic vasculitides (PSVs). Methods: We pro...

Background Primary cardiac affection is common and is a major cause of death in systemic sclerosis (SSc), but there are knowledge gaps regarding the effect of cardiac dysfunction on mortality. Objectives The purpose of this study was to evaluate diastolic function in a large, unselected SSc cohort and assess the effect of diastolic dysfunction (DD...

Background Vitamin D has an important role in the immune system, and has been linked to rheumatoid arthritis (RA) and coronary artery disease (CAD). The exact mechanisms by which vitamin D is involved in these processes are still unclear. Therefore, we wanted to search for differences in expression of genes involved in the vitamin D receptor (VDR)...

Objective: We aimed to jointly investigate the role of antipeptidyl arginine deiminase type 4 antibodies (anti-PAD4) and polymorphisms in the PADI4 gene together with clinical variables in rheumatoid arthritis (RA). Methods: Serum IgG autoantibodies to human recombinant PAD4 were identified by DELFIA technique in 745 patients with RA (366 availa...

Background SLE and MCTD are both chronic immune mediated systemic diseases with similar clinical features. We wanted to compare characteristics and morbidity in addition to mortality prediction models in our large and population based cohorts of SLE and MCTD. Method 243 SLE patients from the Oslo SLE cohort and 145 patients from the Norwegian MCTD...

Objective Recent data has shown that patients with lupus nephritis (LN) have increased mortality. However, no studies have been population based, and few compare mortality data in Systemic Lupus Erythematosus (SLE) patients with and without LN. The aim of our study was to investigate mortality in patients who does or does not develop LN in a popula...

Background The phenotypic stability of mixed connective tissue disease (MCTD) is not clear, and knowledge about disease activity and remission is scarce. We aimed to establish the occurrence of evolution from MCTD to another defined rheumatic condition, and the prevalence and durability of remission after long-term observation. Methods In this larg...

Abstract Background Magnetic resonance imaging (MRI) and computed tomography (CT) angiography have now largely replaced interventional angiography in the diagnoses and follow up of Takayasu arteritis (TAK) but data on the effects of this change of imaging method on diagnostic delay and vascular damage, and detailed data on the effect of different t...

Objective To compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms. Design Adult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital...

Objectives.: To assess the prevalence, extent, progression, functional impact and mortality of interstitial lung disease (ILD) in a nationwide unselected MCTD cohort. Methods.: The study cohort included patients with high-resolution CT lung scans available at baseline (n = 135) and at follow-up (n = 119). The extent of disease was expressed as p...

Background Magnetic resonance imaging (MRI) of thigh muscles is increasingly used to assess disease activity and damage extent in chronic myositis, but the validity of the findings is not clear. Here, the primary aim was to compare thigh MRI findings in patients having chronic myositis associated with anti-synthetase syndrome (ASS) and in matched h...

Objective: Extensive skin disease and renal crisis are hallmarks of anti-RNA polymerase III (RNAP)-positive systemic sclerosis (SSc), while lung and heart involvement data are conflicting. Here, the aims were to perform time-course analyses of interstitial lung disease (ILD) and pulmonary hypertension (PH) in the RNAP subset of a prospective unsel...

Objective: Inclusion body myositis (IBM) is characterised by a combination of inflammatory and degenerative changes affecting muscle. While the primary cause of IBM is unknown, genetic factors may influence disease susceptibility. We conducted the largest genetic association study to date in IBM, investigating immune-related genes using the Immuno...

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...

Objectives: To assess pregnancy outcome in an unselected Takayasu arteritis (TAK) cohort, and identify pregnancy related concerns. Methods: Consenting, female patients with TAK were predominantly recruited from a population based South-east Norway TAK cohort. Additional cases (n=8) were recruited at Oslo University Hospital. Data on the number o...

Purpose of review: In this review, we describe recent progress in the clinical epidemiology of sporadic inclusion body myositis (IBM). Recent findings: In a population-based, retrospective study from Norway, performed with a denominator population of 2.6 million; and with cases defined by the 1997 and/or 2011 European Neuro-Muscular Centre Resea...

Background & aims: The strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Antineutrophil cytoplasmic antibodies (ANCA) have been reported in up to 94% of PSC patients, but their clinical significance and immunogenetic basis are ill defined. We aimed to characterize clinical and genetic associatio...

Objectives: Vitamin D modulates inflammation, and this may explain the observed associations between vitamin D status and disorders driven by systemic inflammation, such as coronary artery disease (CAD) and inflammatory rheumatic diseases (IRDs). The aims of this study were to assess vitamin D status in patients with CAD alone and in patients with...

Purpose of review: Interstitial lung disease (ILD) is the major determinant of morbidity and mortality in systemic sclerosis (SSc). In highly selected SSc patients, it was recently shown that stem cell therapy early in the disease course improved survival and reduced the extent of ILD, providing a rationale for early ILD detection strategies in th...

Significance Fibrosis is a leading cause of death in industrialized countries. Until now, there has been no effective therapy to prevent or counteract the fibrotic process. This article describes the effect of the blockade of a late costimulatory molecule to prevent inflammation-driven skin, lung, and vessel fibrosis and to induce regression of est...

Background The clinical phenotype of the antisynthetase syndrome (AS) has been related with the underlying autoantibody specificity. The typical disease triad (arthritis, myositis, and interstitial lung disease -ILD) is common in anti Jo-1 + AS, whereas isolated ILD is associated with anti PL-7 and PL-12 Ab. The majority of anti Jo-1 + patients wit...

Background Systemic sclerosis (SSc) is a complex, immune-mediated disorder that carries high risk for progressive interstitial lung disease (ILD). CX3CL1 (Fractalkine) is expressed in lungs; and has the ability to act as an adhesion molecule as well as a potent chemoattractant of mononuclear cells via its interaction with CX3CR1. Here, we hypothesi...

Background Vitamin D has an important role in the immune system, and has been linked to inflammation, rheumatoid arthritis (RA) and coronary artery disease (CAD)[1, 2]. However, the exact mechanisms how vitamin D is involved in these processes are still unclear. Objectives To compare expression of vitamin D receptor (VDR) associated genes in the a...

Background Gastrointestinal tract (GIT) involvement in systemic sclerosis (SSc) is common, occurring in 50–90% of the patients (1). However, there is limited knowledge of self reported GIT symptoms affecting patients in daily life. Objectives To describe frequency and severity of self reported gastrointestinal symptoms in a large SSc cohort and ev...

Objectives: To investigate serum levels of endostatin in a well characterised cohort of patients with primary Sjögren's syndrome (pSS) and healthy controls (HC) and assess associations between these mediators and clinical parameters. Methods: All patients (n=144) were recruited from the Norwegian systemic connective tissue disease and vasculitis...

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc-RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods:...

Objective: Interstitial lung disease (ILD) is a major component of the antisynthetase syndrome, but quantitative data on longterm pulmonary outcome in antisynthetase syndrome are limited. In this study, the main aims were to compare pulmonary function tests (PFT) and the 6-min walking distance (6MWD) between patients with antisynthetase syndrome a...

Background: We recently identified a human B-cell population that is naturally autoreactive and tolerized by functional anergy (BND cells). Objective: We sought to identify the molecular mechanism of how anergic autoreactive BND cells escape functional anergy and whether this process is altered in patients with lupus. Methods: Isolated periphe...

The concept of mixed connective tissue disease (MCTD) as a separate connective tissue disease (CTD) has persisted for more than four decades. High titers of antibodies targeting the U1 small nuclear ribonucleoprotein particle (U1 snRNP) in peripheral blood are a sine qua non for the diagnosis of MCTD, in addition to distinct clinical features inclu...

Objectives: Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18 which has been linked to pulmonary inflammation is an interesting candidate, but data have not been consistent. Here, we aimed to assess CCL18 levels in a large, prospective and unselected SSc cohor...