Inflammatory profiles in plasma and cerebrospinal fluid of patients with neurosarcoidosis

Byg, Keld-Erik; Illés, Zsolt; Sejbæk, Tobias; Lambertsen, Kate Lykke; Ellingsen, Torkell; Nielsen, Helle Hvilsted

doi:10.1016/j.jneuroim.2022.577849

Cited by 8 publications

(4 citation statements)

References 86 publications

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“…While angiogenesis has not explicitly been investigated before in CS, dysfunction in cardiac microvasculature, aortic elastic properties and coronary flow reserve have been reported in CS patients (43)(44)(45). Moreover, upregulated angiogenesis has been reported in other forms of sarcoidosis, such as neurosarcoidosis and PS (46,47). Our analysis showed upregulation of angiogenic pathways in both our gene-set enrichment and transcription factor analysis relative to control.…”

Section: Discussionsupporting

confidence: 73%

Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets

Daoud

Lema

Won

et al. 2023

Front. Cardiovasc. Med.

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IntroductionCardiac presentation of autoimmune sarcoidosis, known as cardiac sarcoidosis (CS), is a poorly understood disease with high mortality and low diagnosis rate. While CS is an immunological syndrome, little is known about how cardiac parenchymal and stromal cells mediate its pathogenesis. Moreover, while most current sarcoidosis research is based on research in pulmonary sarcoidosis (PS), it remains unclear how much both presentations of sarcoidosis overlap. To tackle these concerns, we leveraged publicly available sarcoidosis transcriptomic datasets.MethodsTwo publicly available bronchoalveolar lavage single-cell RNA sequencing datasets were integrated to analyze PS relative to control. Additionally, two publicly available cardiac single-nucleus RNA sequencing datasets were integrated to analyze CS relative to control. Following integration, we ran cell-cell communication, transcription factor, and differential expression analyses on parenchymal, stromal, and immune subsets identified in our analysis.ResultsOur analysis revealed that there was an expansion of stromal and immune cells in PS and CS. We also observed upregulation of Th17.1 and attenuated activation transcriptional profiles in the immune cells of CS and PS relative to control. Additionally, we found upregulation of pro-inflammatory and pro-fibrotic transcriptional profiles in the cardiac stromal cells of CS relative to control. We also found that cardiomyocytes exhibited upregulated cardiac stress and proliferation transcriptional profiles in CS relative to control.ConclusionsOur integrative transcriptomic analysis shows that despite tissue-specific differences, there are shared transcriptional trends between CS and PS. It also shows that stromal and parenchymal populations exhibit transcriptional trends that could explain their pathogenic role in CS.

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Section: Discussionsupporting

confidence: 73%

Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets

Daoud

Lema

Won

et al. 2023

Front. Cardiovasc. Med.

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“…Previous studies have tested fampridine against placebo, and the substantial amount of literature demonstrating the positive impact of fampridine on gait function over a 14-day trial period [5,6,36,37] provides support for the current findings. Additionally, the cytokine levels in our participants compared to cytokine levels in healthy controls in a study from our own lab using the same type of test kits and the same time frame as our study [38] verify the results of altered cytokine levels in our sample of pwMS compared with healthy controls.…”

Section: Strength and Limitationsmentioning

confidence: 54%

Performance Measures and Plasma Biomarker Levels in Patients with Multiple Sclerosis after 14 Days of Fampridine Treatment: An Explorative Study

Thorning,

Lambertsen,

Jensen

et al. 2024

IJMS

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Peripheral cytokine levels may serve as biomarkers for treatment response and disease monitoring in patients with multiple sclerosis (pwMS). The objectives were to assess changes in plasma biomarkers in PwMS after 14 days of fampridine treatment and to explore correlations between changes in performance measures and plasma biomarkers. We included 27 PwMS, 14 women and 13 men, aged 52.0 ± 11.6 years, with a disease duration of 17 ± 8.5 years, and an Expanded Disability Status Scale of 6 [IQR 5.0/6.5]. Gait and hand function were assessed using performance tests completed prior to fampridine and after 14 days of treatment. Venous blood was obtained, and chemiluminescence analysis conducted to assess plasma cytokines and neurodegenerative markers. All performance measures demonstrated improvements. Biomarkers showed decreased tumor necrosis factor (TNF) receptor-2 levels. Associations were found between change scores in (i) Six Spot Step Test and Interleukin (IL)-2, IL-8, and IL-17 levels; (ii) timed 25-foot walk and interferon-γ, IL-2, IL-8, TNF-α, and neurofilament light levels, and (iii) 12-Item Multiple Sclerosis Walking Scale and IL-17 levels. The associations may reflect increased MS-related inflammatory activity rather than a fampridine-induced response or that a higher level of inflammation induces a better response to fampridine.

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“…On the contrary, peripheral blood lymphocytes were significantly lower in NS patients compared to healthy control. Interestingly, the most frequent symptom in this NS group was headache (60%), followed by vertigo (55%) and tinnitus (50%) [65]. Peripheral T cell exhaustion and dysfunctional Treg cells have been implicated in the pathogenesis of sarcoidosis [61].…”

Section: Shared Molecular Mechanisms Between Migraine and Sarcoidosismentioning

confidence: 86%

“…Interestingly, endothelial dysfunction with the increase in the serum levels of the intracellular adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAM) has been also demonstrated in children and young adults with migraine [75]. sVCAM-1 levels have also been found significantly higher in subjects with more frequent migraine; in the same study, IL-6 was the only inflammatory mediator that was found to be higher in migraine patients than controls, when adjusting for age and sex, but without reaching statistical significance [65]. Notably, the decrease in VCAM-1 serum levels has been correlated to the therapeutic efficacy of alpha-lipoic acid (ALA) supplementation, used as an adjunct treatment in a clinical trial involving a population of female migraine patients without aura.…”

Section: Shared Molecular Mechanisms Between Migraine and Sarcoidosismentioning

confidence: 89%

Common Clinical and Molecular Pathways between Migraine and Sarcoidosis

Tana¹,

García‐Azorín

Cinetto

et al. 2023

IJMS

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Migraine and sarcoidosis are two distinct medical conditions that may have some common biological and clinical pathways. Sarcoidosis is a chronic granulomatous disease characterized by the formation of granulomas in various organs, including the lungs, skin, cardiovascular system, lymph nodes, and brain. Migraine is a common comorbidity in sarcoidosis patients and a common neurological disorder characterized by recurrent headaches that can be accompanied by other symptoms, such as nausea, vomiting, and sensitivity to light and sound. There have been several reports of individuals with neurosarcoidosis experiencing migraines, though the exact relationship between the two disorders is not well understood. Both conditions have been associated with inflammation and the activation of the immune system. In sarcoidosis, the formation of granulomas is thought to be an immune response to the presence of an unknown antigen. Similarly, the pain and other symptoms associated with migraines are thought to be caused by inflammation in the brain and the surrounding blood vessels. There is also evidence to suggest an interplay of environmental and genetic factors playing a role in both conditions, but evidence is inconsistent with the hypothesis of shared genetic susceptibility. This review aims to illustrate common clinical and biological pathways between migraine and sarcoidosis, including inflammation and dysregulation of the immune system, with a focus on the cumulative burden of concurrent disorders and therapeutic implications.

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Inflammatory profiles in plasma and cerebrospinal fluid of patients with neurosarcoidosis

Cited by 8 publications

References 86 publications

Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets

Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets

Performance Measures and Plasma Biomarker Levels in Patients with Multiple Sclerosis after 14 Days of Fampridine Treatment: An Explorative Study

Common Clinical and Molecular Pathways between Migraine and Sarcoidosis

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