Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood. METHODS: To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP). RESULTS: Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression. CONCLUSIONS: Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.

Impacts of inflammatory cytokines on depression: a cohort study.

BACKGROUND: Inflammatory factors are associated with depression. We seek to investigate the correlation between inflammatory cytokines and prognosis of depression or suicidal ideation and behavior at 3 months in depression patients. METHODS: Eighty-two depressed outpatients were recruited and treated as usual. Plasma cytokines were measured at baseline. Patients were followed up with Patient Health Questionnaire-9 and suicidal ideation and behavior according to the item 3 of Hamilton depression scale for 3 months. RESULTS: Compared to the depression patients with low level of interleukin-1ß, the high one had severe depressive symptoms at month 2 and 3 (B 0.92, P < 0.01; B 0.86, P = 0.02; respectively). The incidence of suicidal ideation or behavior was 18.3% at 3 months. Depression patients with high levels of tumor necrosis factor-α showed high risk of suicidal ideation and behavior than the low one (OR 2.16, 95% CI 1.00-4.65, P = 0.04). CONCLUSIONS: High levels of interleukin-1ß and tumor necrosis factor-α were predictive of middle-term severe depressive symptoms and suicidal ideation and behavior respectively.

Effects of ultrasound-guided erector spinae plane block on postoperative analgesia and plasma cytokine levels after uniportal VATS: a prospective randomized controlled trial.

PURPOSE: Although uniportal video-assisted thoracoscopic surgery (VATS) has been widely used, the associated postoperative pain is still severe. Currently, a variety of regional anesthesia methods have been used to relieve postoperative pain. In our study, we wanted to evaluate the effectiveness of ultrasound-guided erector spinae plane block (ESPB) as a postoperative analgesia after uniportal VATS. METHODS: Eighty patients scheduled to undergo uniportal VATS were randomly divided into Group ESP and Group C. In Group ESP, the patients underwent ultrasound-guided ESPB under general anesthesia before surgery, while Group C was set as blank control group without ESPB. The primary outcome was the sufentanil dose within 24 h after surgery. The secondary outcomes mainly included postoperative pain scores at 2, 4, 8, and 24 h evaluated using a numeric rating scale (NRS), intraoperative opioid dosage, levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the plasma, side effect profile, and length of postoperative hospital stay. RESULTS: Postoperative sufentanil consumption (32.5 ± 6.3 µg vs. 42.8 ± 7.6 µg, P < 0.001) was significantly lower in Group ESP than in Group C. Intraoperative sufentanil consumption was significantly lower in Group ESP than in Group C (P < 0.001). The postoperative NRS score and levels of inflammatory cytokines were significantly lower in Group ESP than in Group C (P < 0.05). CONCLUSIONS: Ultrasound-guided ESPB decreased the consumption of sufentanil both postoperatively and intraoperatively for patients undergoing uniportal VATS and appeared to be an effective treatment option.

Racial Disparities in Plasma Cytokine and Microbiome Profiles.

BACKGROUND: Many health issues prevalent in African American (AA) populations are associated with chronic inflammation and related health conditions, including autoimmune diseases, infectious diseases, neurologic disorders, metabolic syndromes, and others. The current study aims to understand plasma microbiome translocation as a potential trigger for chronic inflammation. METHODS: In this study, 16 Caucasian American (CA) and 22 African American (AA) healthy individuals were recruited. Microbial DNA was isolated from the plasma samples and sequenced via microbial 16S rRNA V3-4 sequencing. The plasma levels of 33 cytokines and chemokines were evaluated. The proinflammatory microbiomes were verified using human THP-1 cells in vitro. RESULTS: The plasma levels of IL-6, IL-15, MIP-1α, MIP-1ß, and MIP-3α were higher in the AA people, whereas IL-1α and IL-27 were elevated in the CA people. The plasma microbiomes exhibited eight bacterial genera/phyla differentially enriched in the CA and AA people. Given the critical role of IL-6 in chronic inflammation and associated diseases, we identified five bacteria genera significantly associated with IL-6. The abundance of Actinomyces was positively correlated with the plasma IL-6 level (r = 0.41, p = 0.01), while the abundance of Kurthia (r = -0.34, p = 0.04), Noviherbaspirillum (r = -0.34, p = 0.04), Candidatus Protochlamydia (r = -0.36, p = 0.03), and Reyranella (r = -0.39, p = 0.02) was negatively correlated with this. Finally, the THP-1 cells treated with heat-killed bacteria produced higher levels of IL-6 in vitro in response to the Actinomyces species compared to the species in the genus either uncorrelated or negatively correlated with IL-6. CONCLUSIONS: This is the first study to report potential blood microbiome translocation as a driver for persistently elevated IL-6 levels in the periphery in healthy AA versus CA people. Understanding the plasma microbiome linked to the IL-6 levels in people with different racial backgrounds is essential to unraveling the therapeutic approaches to improve precision medicine.

Changes in NK Cell Subsets and Receptor Expressions in HIV-1 Infected Chronic Patients and HIV Controllers.

Natural killer (NK) cells are major effectors of the innate immune response and purported to play an influential role in the spontaneous control of HIV infection. In the present study, we compared the phenotypes of NK cells in the peripheral blood of three groups of subjects with chronic HIV-1 infection, HIV controllers, and healthy donors. The results showed that CD56+/CD16- NK cell subsets decreased in chronic patients and remained unchanged in controllers. Notably, we found that people living with chronic HIV-1 infection had suppressed NKp80, NKp46, and NKG2D expressions on NK cells compared to healthy donors, while HIV controllers remained unchanged. In contrast, NKG2D expression was substantially higher in controllers than in chronic patients (M=97.67, p<0.001). There were no significant differences in inhibitory receptors KIR3DL1 and KIR2DL1 expressions. In addition, plasma cytokine IFN-γ, TNF-α and IL-12showed higher levels in HIV controllers compared to chronic patients. Overall, our study revealed that, as compared to chronic patients, HIV controllers show an increased activating receptors expression and higher number ofCD56+/CD16-NK cell subset, with increased expression levels of plasma cytokines, suggesting that higher immune activation in controllers may have a key role in killing and suppressing HIV.

Upregulation of OLR1 and IL17A genes and their association with blood glucose and lipid levels in femoropopliteal artery disease.

Oxidized low-density lipoprotein receptor 1 (OLR1) and interleukin 17A (IL17A) have pro-inflammatory roles in the development of cardiovascular disorders. The present study evaluated the association of OLR1 and IL17A and their polymorphisms with the development of femoropopliteal (FP) artery disease. The mRNA expression of OLR1 and IL17A in peripheral blood mononuclear cells as well as the frequency of OLR1 rs11053646 and IL17A rs8193037 and rs3819025 polymorphisms were assessed by polymerase chain reaction in 70 patients with FP artery disease and 80 age-matched disease-free controls. Furthermore, the levels of plasma cytokines were assessed by multiplex immunoassay. OLR1 and IL17A mRNA expression was significantly higher in patients with FP artery disease compared with that in controls (P<0.001). No significant difference was observed in the genotypic frequencies of OLR1 rs11053646 (P=0.87) or in IL17A rs8193037 and rs3819025 (P=0.80 and 0.92, respectively) polymorphisms between patients with FP artery disease and controls. Plasma IL4, -6, -10, -22, -31 and -33 as well as soluble cluster of differentiation 40 ligand and tumor necrosis factor-α levels were significantly increased among FP artery disease patients compared with controls (P<0.05). Furthermore, OLR1 expression was positively correlated with triglyceride (r=0.463, P<0.001), low-density lipoprotein cholesterol (r=0.507, P<0.001) and total cholesterol levels (r=0.357, P=0.006) in patients with FP artery disease. To the best of our knowledge, the present study was the first to identify an association between OLR1 and IL17A genes and FP artery disease. OLR1 and IL17A mRNA transcripts may be associated with blood lipid parameters and with the development of FP artery disease.