Publications by authors named "Julius Lindblom"

Objectives: Early trials of CD19-chimeric antigen receptor (CAR) T cell therapy in systemic lupus erythematosus (SLE) show promise, but the molecular mechanisms underlying its disease-modifying effects remain unclear. We aimed to compare biological profiles and alterations following CD19-CAR T cell versus standard pharmacotherapy in SLE.

Methods: Pseudo-bulk gene expression derived from single-cell RNA sequencing of peripheral blood mononuclear cells from 7 SLE patients before and after CD19-CAR T cell therapy was compared with whole-blood transcriptome data from 30 SLE patients in remission on standard pharmacotherapy and 31 SLE patients before and 6 months after treatment with rituximab, belimumab, or cyclophosphamide.

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Objectives: To gain insights into the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) and identify potential drug targets through investigation of whole-blood human transcriptome.

Methods: We analysed differentially expressed genes in peripheral blood from active central nervous system (CNS) lupus (n = 26) and active non-neuropsychiatric SLE (n = 38) patients versus healthy controls (n = 497) from the European PRECISESADS project (NTC02890121). We further explored dysregulated gene modules in active CNS lupus and their correlation with serological markers.

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Objectives: In response to the urgent unmet needs of heterogeneity, unpredictability, and diagnostic delay in systemic lupus erythematosus (SLE), we aimed to identify and validate new immunoglobulin (Ig)G and IgA autoantibody specificities.

Methods: Using a KoRectly EXpressed technology-based microarrays (i-Ome Discovery; Sengenics), we screened for circulating IgG and IgA autoantibodies against 1609 proteins in 2 independent cohorts (discovery: NTC02890121; validation: NCT02890134) comprising patients with SLE (n = 199 and n = 30), primary Sjögren's disease (n = 115 and n = 31), and systemic sclerosis (n = 115 and n = 24), and healthy controls (HCs; n = 111 and n = 84), respectively.

Results: We identified and validated 5 IgG (anti-Lin-28 homolog A [LIN28A], anti-HNRNPA2B1, anti-HMG20B, anti-HMGB2, and anti-alpha-globin transcription factor CP2 [TFCP2]) and 4 IgA (anti-LIN28A, anti-HMG20B, anti-SUB1, and anti-TFCP2) autoantibodies that demonstrated high specificity for SLE (0.

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Objectives: This study aimed to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE).

Methods: Plasma samples were screened for IgG and IgA seroreactivity against 1609 protein autoantigens using a microarray (i-Ome Discovery; Sengenics). We determined differentially abundant autoantibodies (daAAbs) in patients with SLE vs healthy controls within a discovery (n = 196 vs n = 110; NTC02890121) and an independent validation cohort (n = 30 vs n = 83; NCT02890134) from the European PRECISESADS project.

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Objectives: To determine belimumab efficacy assessed using the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) in patients with systemic lupus erythematosus (SLE) from phase III belimumab randomised controlled trials (RCTs).

Methods: A post hoc analysis was carried out on five RCTs in active adult SLE: four with intravenous (BLISS-52, BLISS-76, BLISS-NEA, EMBRACE) and one with subcutaneous belimumab (BLISS-SC). The 52-week landmark assessments were analysed across trials.

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Objectives: To determine factors associated with reports of EuroQol 5-Dimensions (EQ-5D) full health state (FHS) before and after a trial intervention in patients with SLE, resorting to machine learning algorithms.

Methods: We conducted a post hoc analysis of two phase 3 clinical trials of belimumab (BLISS-52, BLISS-76). Demographic, laboratory and clinical features were retrieved and the Monte Carlo Feature Selection algorithm was employed, then further refined upon consideration of collinearity and clinical relevance.

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Objective: To determine SLE endotypes according to B cell immunophenotyping and serological profile and assess endotypes' response to belimumab.

Methods: We analysed data from 796 patients with SLE from the phase III trial BLISS-SC. Unsupervised machine learning employing factor analysis of mixed data (FAMD) and subsequent clustering determined endotypes based on B cell immunophenotyping and serological profiles.

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Objective: To determine the efficacy of belimumab on mucocutaneous manifestations of SLE in a large integrative analysis.

Methods: Using data from five phase III clinical trials (BLISS-52; BLISS-76; BLISS-NEA; EMBRACE; BLISS-SC; N = 3086), we investigated the effect of belimumab vs. placebo on top of standard therapy on inducing improvement in mucocutaneous BILAG (mcBILAG) and mucocutaneous SLE Disease Activity Index 2000 (mcSLEDAI-2K), and on preventing mcBILAG flares.

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Objectives: DORIS remission, based on clinical activity, and lupus low disease activity state (LLDAS), which includes serological markers, are protective targets in SLE. However, it remains unclear whether their prognostic impact is influenced by serum anti-dsDNA and complement levels.

Methods: We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) totalling 45 254 monthly visits.

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Article Synopsis
  • This study explored the adverse events (AEs) related to COVID-19 vaccination in patients with rheumatoid arthritis (RA) as part of the COVAD-2 study, which surveyed participants from February to June 2022.
  • It included 7203 participants, including 1423 RA patients, and found that RA patients reported higher rates of both major and minor AEs compared to healthy controls, and even more when compared to those with other autoimmune diseases.
  • Active RA significantly increased the risk of major AEs and hospitalization, while patients on certain medications like methotrexate or TNF inhibitors experienced fewer AEs than those not on these treatments.
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  • The study aimed to understand how systemic lupus erythematosus (SLE) progresses after starting therapy, focusing on different patient responses and outcomes.
  • Researchers analyzed data from 2868 patients across four clinical trials, identifying four distinct disease evolution characteristics based on both clinical measures and patient-reported outcomes.
  • The findings suggest that categorizing patients into these trajectories could help personalize treatments and improve future clinical study designs, as no single factor can predict how SLE will progress.
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Background: Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE.

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  • The study aimed to compare the occurrence of breakthrough COVID-19 infections (BIs) in fully vaccinated patients with systemic lupus erythematosus (SLE) against those with other rheumatic autoimmune diseases (rAIDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs).
  • Results showed that 10.7% of SLE patients reported at least one BI, with frequencies similar to HCs and nrAID patients but higher than those with other rAIDs.
  • Overall, vaccinated SLE patients experienced comparable levels of COVID-19 infection frequency and severity as healthy individuals, with no significant association found between demographic factors or treatments and BIs in SLE patients.
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Objective: To investigate the association between neuropsychiatric systemic lupus erythematosus (NPSLE) and SLICC/ACR damage index (SDI) items, especially non-neuropsychiatric items.

Methods: Baseline data from five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) were analysed. NPSLE involvement was defined as NP BILAG A/B/C/D (n = 272); NP BILAG E denoted non-neuropsychiatric SLE (n = 3273).

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Introduction: Current therapeutic management of lupus nephritis (LN) fails to induce long-term remission in over 50% of patients, highlighting the urgent need for additional options.

Methods: We analyzed differentially expressed genes (DEGs) in peripheral blood from patients with active LN ( = 41) and active nonrenal lupus ( = 62) versus healthy controls (HCs) ( = 497) from the European PRECISESADS project (NTC02890121), and dysregulated gene modules in a discovery ( = 26) and a replication ( = 15) set of active LN cases.

Results: Replicated gene modules qualified for correlation analyses with serologic markers, and regulatory network and druggability analysis.

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Objectives: Substantial proportions of patients with SLE report poor health-related quality of life (HRQoL). Our objective was to investigate the impact of neuropsychiatric involvement (NP) in SLE on patient-reported outcomes.

Methods: We analysed data from four phase III trials (BLISS-52, BLISS-76, BLISS-SC, EMBRACE; N = 2968).

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Objectives: To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE).

Methods: We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission.

Results: We analysed data from 321 patients; 40.

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Article Synopsis
  • The study investigates delayed adverse events (DAEs) from COVID-19 vaccinations in patients with systemic lupus erythematosus (SLE) compared to other autoimmune diseases and healthy individuals, with a focus on data scarcity impacting vaccine hesitancy among immunocompromised individuals.
  • The research, conducted through a global online survey of over 7200 individuals, found that SLE patients experienced significantly more major DAEs and hospitalizations post-vaccination than healthy controls and had higher rates of severe rashes compared to those with other rheumatic diseases.
  • The findings suggest a need for careful monitoring of SLE patients post-vaccination due to their elevated risk of adverse events, particularly after receiving the Moderna vaccine.
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Introduction: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease that presents a challenge for clinicians. To identify potential biomarkers for diagnosis and disease activity in SLE, we investigated a selected yet broad panel of cytokines and autoantibodies in patients with SLE, healthy controls (HC), and patients with other autoimmune diseases (AIDs).

Methods: Serum samples from 422 SLE patients, 546 HC, and 1223 other AIDs were analysed within the frame of the European PRECISESADS project (NTC02890121).

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Introduction: Belimumab was recently approved for treating lupus nephritis (LN), yet LN cases during belimumab treatment given for nonrenal causes have been reported. Identification of reliable signals of impending flare is imperative.

Methods: We evaluated belimumab efficacy in preventing renal flares and factors associated with renal flare occurrence in nephritis-naïve patients with systemic lupus erythematosus (SLE) who are receiving add-on belimumab or placebo in 5 phase 3 clinical trials using Cox regression analysis.

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Objective: To investigate whether abnormal BMI is associated with health-related quality of life (HRQoL) impairments, defined as patient-reported problems within the different dimensions of the three-level EQ-5D (EQ-5D-3L), before and after treatment for active systemic lupus erythematosus (SLE).

Patients And Methods: We conducted a post-hoc analysis of data from two phase III clinical trials of belimumab in SLE, i.e.

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Article Synopsis
  • This study investigates the molecular characteristics of proliferative lupus nephritis (LN) through imaging mass cytometry, focusing on the spatial profiles of 50 proteins in LN and healthy kidneys.
  • Proliferative LN is characterized by podocyte loss, significant immune cell infiltration (primarily memory T-cells and macrophages), and notable changes in both glomeruli and tubulointerstitial areas.
  • The research highlights the role of macrophages in the disease and identifies features such as fibronectin presence and epithelial-to-mesenchymal transition in tubular cells, showcasing the effectiveness of IMC in understanding the complex architecture of LN at the protein level.
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Objective: To identify determinants of neuropsychiatric (NP) flares in patients with SLE treated for active SLE yet no ongoing severe NPSLE with non-biologic standard therapy plus belimumab or placebo.

Methods: We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, EMBRACE; n = 3638) after exclusion of patients with baseline NP BILAG A. Factors associated with NPSLE flare, defined as a new NP BILAG A or B, were investigated using Cox regression.

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