The Transcriptomic Profile of Monocytes from Patients With Sjögren’s Syndrome Is Associated With Inflammatory Parameters and Is Mimicked by Circulating Mediators

Lopes, Ana P; Bekker, Cornelis P. J.; Hillen, Maarten R; Blokland, Sofie L M; Hinrichs, Anneline C.; Pandit, Aridaman; Kruize, Aike A.; Roon, Joël A G van

doi:10.3389/fimmu.2021.701656

Cited by 18 publications

(17 citation statements)

References 63 publications

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“…Other mechanisms, such as small vessel vasculitis targeting the CNS, could also be involved in dementia onset in pSS patients. Another underlying pathophysiological pathway linking cognitive decline and pSS could be interferon (INF) pathway dysregulations [ 37 , 38 , 39 ]. However, our preliminary data need further investigation to determine the exact underlying immunological mechanisms behind the dementia and cognitive troubles in pSS patients.…”

Section: Discussionmentioning

confidence: 99%

Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients

Goulabchand

Gabelle

Ayrignac

et al. 2022

JCM

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Primary Sjögren’s syndrome (pSS) can be associated with neurological and cognitive involvement, negatively affecting patients’ quality of life. The aim of this study was to assess whether pSS patients are at higher risk of hospitalization for neurological diseases. Through a nationwide retrospective study using the French Health insurance database (based on International Classification for Disease codes, ICD-10), we selected patients hospitalized with new-onset pSS between 2011 and 2018. We compared the incidence of hospitalization for dementia, multiple sclerosis (MS), encephalitis, and peripheral neuropathy with an age- and sex-matched (1:10) hospitalized control group. Adjusted Hazard Ratios (aHR) considered confounding factors, particularly socio-economic status and cardiovascular diseases. We analyzed 25,661 patients hospitalized for pSS, compared with 252,543 matched patients. The incidence of hospitalization for dementia was significantly higher in pSS patients (aHR = 1.27 (1.04–1.55); p = 0.018), as well as the incidence of hospitalization for MS, encephalitis, and inflammatory polyneuropathies (aHR = 3.66 (2.35–5.68), p < 0.001; aHR = 2.66 (1.22–5.80), p = 0.014; and aHR = 23.2 (12.2–44.5), p < 0.001, respectively). According to ICD-10 codes, pSS patients exhibited a higher incidence of hospitalization for dementia, encephalitis, MS, and peripheral neuropathies than controls. Physicians must be aware of these neurological risks to choose the most appropriate diagnostic work-up.

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Section: Discussionmentioning

confidence: 99%

Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients

Goulabchand

Gabelle

Ayrignac

et al. 2022

JCM

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“…Trained immunity is mediated by changes in cellular metabolism, including increased glycolysis ( 3 ). Monocytic expression of key genes involved in cellular metabolic pathways associated with trained immunity were analyzed using a publicly available RNA sequencing dataset of pSS and HC monocytes ( 18 ). Monocytes from pSS patients expressed significantly lower transcript levels of the mTOR signaling pathway components PIK3R1 and EIF4EBP1 , the glycolytic enzymes PKM and PGM1 and the TCA-cycle enzymes MDH2 and CS ( Figure S9 ; Tables S2 , 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Paired-end raw FASTQ files were downloaded from the GEO database using GEO Series accession number GSE173670 ( 18 ), and were analyzed with the nf-core/RNA-seq pipeline (v3.1) using Nextflow (21.05.0.edge) and its default settings ( 33 , 34 ). Quality of the sequencing was reported with FastQC (v11.9).…”

Section: Methodsmentioning

confidence: 99%

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Trained Immunity in Primary Sjögren’s Syndrome: Linking Type I Interferons to a Pro-Atherogenic Phenotype

et al. 2022

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BackgroundTrained immunity – or innate immune memory – can be described as the long-term reprogramming of innate immune cells towards a hyperresponsive state which involves intracellular metabolic changes. Trained immunity has been linked to atherosclerosis. A subgroup of patients with primary Sjögren’s syndrome (pSS) exhibits systemic type I interferon (IFN) pathway activation, indicating innate immune hyperactivation. Here, we studied the link between type I IFNs and trained immunity in an in vitro monocytic cell model and peripheral blood mononuclear cells (PBMCs) from pSS patients.MethodsThe training stimuli heat killed Candida albicans, muramyl dipeptide, IFNβ, and patient serum were added to THP-1 cells for 24 hours, after which the cells were washed, rested for 48 hours and subsequently re-stimulated with LPS, Pam3Cys, poly I:C, IFNβ or oxLDL for 4-24 hours. PBMCs from pSS patients and healthy controls were stimulated with LPS, Pam3Cys, poly I:C or IFNβ for 0.5-24 hours.ResultsTraining with IFNβ induced elevated production of pro-atherogenic cytokines IL-6, TNFα and CCL2, differential cholesterol- and glycolysis-related gene expression, and increased glucose consumption and oxLDL uptake upon re-stimulation. Type I IFN production was increased in Candida albicans- and IFNβ-trained cells after LPS re-stimulation, but was reduced after poly I:C re-stimulation. Training with muramyl dipeptide and IFNβ, but not Candida albicans, affected the IFN-stimulated gene expression response to IFNβ re-stimulation. PBMCs from pSS patients consumed more glucose compared with healthy control PBMCs and tended to produce more TNFα and type I IFNs upon LPS stimulation, but less type I IFNs upon poly I:C stimulation.ConclusionsType I IFN is a trainer inducing a trained immunity phenotype with pro-atherogenic properties in monocytes. Conversely, trained immunity also affects the production of type I IFNs and transcriptional response to type I IFN receptor re-stimulation. The phenotype of pSS PBMCs is consistent with trained immunity. This connection between type I IFN, trained immunity and cholesterol metabolism may have important implications for pSS and the pathogenesis of (subclinical) atherosclerosis in these patients.

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“…Previous studies indicate that SARD patients have increased proportions of monocytes in their peripheral blood, particularly those of the intermediate and non-classical type (52)(53)(54)(55). Nonclassical monocytes have been shown to have an increased capacity to secrete pro-inflammatory molecules and present antigens to T cells, as compared to classical monocytes (56,57).…”

Section: Accumulation Of Innate Immune Populations Favoring Productio...mentioning

confidence: 99%

Altered Balance of Pro-Inflammatory Immune Cells to T Regulatory Cells Differentiates Symptomatic From Asymptomatic Individuals With Anti-Nuclear Antibodies

et al. 2022

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Systemic Autoimmune Rheumatic Diseases (SARDs) are characterized by the production of anti-nuclear antibodies (ANAs). ANAs are also seen in healthy individuals and can be detected years before disease onset in SARD. Both the immunological changes that promote development of clinical symptoms in SARD and those that prevent autoimmunity in asymptomatic ANA+ individuals (ANA+ NS) remain largely unexplored. To address this question, we used flow cytometry to examine peripheral blood immune populations in ANA+ individuals, with and without SARD, including 20 individuals who subsequently demonstrated symptom progression. Several immune populations were expanded in ANA+ individuals with and without SARD, as compared with ANA- healthy controls, particularly follicular and peripheral T helper, and antibody-producing B cell subsets. In ANA+ NS individuals, there were significant increases in T regulatory subsets and TGF-ß1 that normalized in SARD patients, whereas in SARD patients there were increases in Th2 and Th17 helper cell levels as compared with ANA+ NS individuals, resulting in a shift in the balance between inflammatory and regulatory T cell subsets. Patients with SARD also had increases in the proportion of pro-inflammatory innate immune cell populations, such as CD14+ myeloid dendritic cells, and intermediate and non-classical monocytes, as compared to ANA+ NS individuals. When comparing ANA+ individuals without SARD who progressed clinically over the subsequent 2 years with those who did not, we found that progressors had significantly increased T and B cell activation, as well as increased levels of LAG3+ T regulatory cells and TGF-ß1. Collectively, our findings suggest that active immunoregulation prevents clinical autoimmunity in ANA+ NS and that this becomes impaired in patients who progress to SARD, resulting in an imbalance favoring inflammation.

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The Transcriptomic Profile of Monocytes from Patients With Sjögren’s Syndrome Is Associated With Inflammatory Parameters and Is Mimicked by Circulating Mediators

Cited by 18 publications

References 63 publications

Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients

Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients

Trained Immunity in Primary Sjögren’s Syndrome: Linking Type I Interferons to a Pro-Atherogenic Phenotype

Altered Balance of Pro-Inflammatory Immune Cells to T Regulatory Cells Differentiates Symptomatic From Asymptomatic Individuals With Anti-Nuclear Antibodies

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