Serum Levels Of CXCL10 Research Articles

High serum levels of CXCL13 predict lower response to csDMARDs in both ACPA-positive and ACPA-negative early rheumatoid arthritis.

Increased circulating levels of CXCL13 reflect synovial production and indicate immune dysregulation in patients with rheumatoid arthritis (RA). Here we tested whether CXCL13 predicts response to first-line treatment with methotrexate (MTX) in patients with early RA, independently and in association with anti-citrullinated protein antibodies (ACPA) and IgM-rheumatoid factor (RF). A prospective cohort of 243 early RA patients undergoing treat-to-target with MTX was evaluated. CXCL13, ACPA and IgM-RF were determined on baseline sera. Short-term variations of CXCL13 were measured after 2 months. The association of high CXCL13 (≥100 pg/ml) with disease remission after 6 months and escalation to second-line therapies within year 2 was evaluated in the total population and in ACPA-subgroups separately. High levels of CXCL13 were found in 53.6% of ACPA-positive and 31.5% of ACPA-negative patients, with minimal association with disease activity and RF. Serum CXCL13 remained stable after 2 months. High baseline CXCL13 independently predicted failure to achieve remission and more frequent requirement of second-line treatment in ACPA-positive patients, with adjusted ORs in the range of 0.17-0.49 for remission and 6.75 for second-line treatment. In ACPA-negative patients with high CXCL13, remission occurred at the expense of higher doses of MTX, and levels of CXCL13 predicted MTX escalations with an adjusted OR (95% CI) of 2.69 (1.35-5.34). High serum levels of CXCL13 identify a subgroup of RA patients who are more refractory to first-line treatment with MTX. CXCL13 appears a promising biomarker of response to MTX in both ACPA-positive and -negative early RA.

Metformin Exhibits Anti-Inflammatory Effects by Regulating microRNA-451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis.

Osteoarthritis (OA) is the most common cause of chronic disability in joints among older individuals. The primary goal of OA treatment is pain relief to improve the quality of life. Inflammation and aging are involved in the pathogenesis of pain in OA. In this study, we evaluated the ability of metformin to regulate microRNAs, such as miR-451 and miR-15b, and their target proteins, CXCL16 and B cell leukemia/lymphoma 2 (BCL-2), involved in inflammation and apoptosis. In this double-blind placebo-controlled clinical trial, patients were randomly divided into two groups: one receiving metformin and the other receiving a placebo for four months (starting at 0.5 g/day for the first week, increasing to 1 g/day for the second week, and increasing to 1.5 g/day for the remaining period). In addition to evaluating the clinical response using the Knee Injury and Osteoarthritis Outcome Score questionnaire, miR-451 and miR-15b expression levels were detected using real-time polymerase chain reaction. The serum levels of CXCL16 and BCL-2 were evaluated using enzyme-linked immunosorbent assay kits before (time zero) and after treatment (month four). Metformin increased miR-451 expression levels simultaneously with pain reduction, whereas miR-15b expression did not change significantly after four months of treatment. Also, metformin decreased the serum levels of BCL-2 and CXCL16 in patients with OA. The effects of metformin in reducing pain can be attributed to many factors, including its anti-inflammatory and antiaging effects. Our findings suggest that metformin may reduce pain and inflammation in patients with OA through the regulation of miR-451/CXCL16 and BCL-2.

Increased Cytokine Levels in Seronegative Myositis: Potential Th17 Immune Response Implications

Th17 cells are known for producing IL-17 and their role in the pathogenesis of various autoimmune diseases, including myositis. Likewise, the participation of the IL-23/IL-17 pathway in autoimmunity has been confirmed. In this study, we aimed to evaluate the behavior of cytokines in myositis, focusing on the autoantibodies profile and the myositis core set measures. Twenty-five myositis patients were enrolled in this cross-sectional study. An expert rheumatologist evaluated the myositis core set measures. Serum levels of cytokines and chemokines were quantified using the LEGENDplex Multi-Analyte Flow Assay Kit from BioLegend. The autoantibodies detection was carried out using the line-blot assay kit Euroline: Autoimmune Inflammatory Myopathies from EUROIMMUN. We found higher serum levels of IL-33, CXCL8, IL-6, IL-23, and IL-12p70 in seronegative patients. A multiple linear regression analysis revealed that MYOACT scores could be predicted by the increment of IL-23 and the decrement of CCL2, IL-10, and CXCL8 serum levels. These findings suggest that the immune response in seronegative myositis patients exhibits an IL-23-driven Th17 immune response. The relevance of this discovery lies in its potential therapeutic implications. Insights into the IL-23-driven Th17 immune response in seronegative patients highlight the potential for targeted therapies aimed at modulating Th17 activity.

A-239 Cxcl10 induced gut dysbiosis exacerbates acute lung injury and secondary infection in influenza by inhibiting il22

Abstract Background Secondary infections are the most cause of severe pulmonary injury and death in influenza. CXCL10, known as interferon γ-induced protein 10(IP-10), is highly upregulated in response to IFN-γstimulation during influenza. Previous studies show that CXCL10 contributes to bacteria co-infections and worse finales in influenza. However, the underlying mechanisms by which CXCL10 facilitate secondary infections remains unclear. Emerging evidences show that influenza virus infections disturb the composition and function of gut microbiota, which in turn influences the infection process. Herein, we aimed to explore whether CXCL10 could affect the progress of influenza infection and secondary infection in a gut microbiota dependent manner. Methods CXCL10 knockout mice were used to determine the role of CXCL10 in staphylococcus aureus co-infection after influenza A virus (IAV) infection. Lung tissues from CXCL10 knockout mice were collected for Transcriptomics sequencing. Feces from mice and clinicals including IAV patients and healthy individuals were collected for Metagenomic sequencing. Paired serum samples were collected for Metabolomic sequencing. QRT-PCR was performed to determine the expression of inflammatory factors in lung tissues from CXCL10 knockout mice. Elisa assays were used to measure the serum expression levels of CXCL10 and IL22. Flow cytometry was applied to detect the proportion of IL22+ cells. Fecal microbiota transplantation (FMT) was applied to confirm that CXCL10 plays an adverse role in acute lung injury and staphylococcus aureus co-infection after IAV infection by disrupting intestinal microbiome homeostasis. Results CXCL10 aggravated acute lung injury and promoted staphylococcus aureus coinfection after IAV infection. Transcriptomics sequencing results suggests improved cell membrane integrity and regeneration of epithelial cells after IAV infection in CXCL10 knockout mice with an upregulation of integrity proteins. CXCL10 knockout significantly increased the expression levels of IL22 without influencing virus duplication. rh-IL22 protects lung epithelial cell from staphylococcus aureus co-infection in influenza and increased the expression of tight junction proteins. The gut microbiome shows different structures between wild type mice and knockout mice, as well as clinical samples according to serum CXCL10 expression levels. We found some genera were markedly increased in knockout mice and patients with low serum CXCL10 expression levels including Lactobacillus, Lachnospiraceae, Oscillibacter, Odoribacter, Eubacterium. FMT from patients with low serum CXCL10 levels and healthy individuals ameliorating lung pathological damage. Conclusions This study interpreted that CXCL10 exacerbates acute lung injury and secondary infection in influenza by inducing gut dysbiosis, suggesting that balancing the gut flora could be assistant treatments to protect from acute lung injury and secondary infections in influenza. And IL22 may be a potential mediating factor between gut-lung axis to improve epithelial integrity.

CXCL10 predicts autoimmune features and a favorable clinical course in patients with IIP: post hoc analysis of a prospective and multicenter cohort study

BackgroundInterstitial pneumonia with autoimmune features (IPAF), which does not meet any of the criteria for connective tissue diseases (CTD), has been attracting an attention in patients with idiopathic interstitial pneumonia (IIP). However, the biomarkers that reflect the clinical course of these patients have not been fully elucidated.ObjectiveTo identify useful serum biomarkers reflecting CTD-related features and favorable prognoses in patients with IIP.MethodsThis was a post hoc analysis of a prospective and multicenter cohort study between 2015 and 2020. Newly diagnosed patients with IIP were consecutively enrolled, and 74 autoimmune features and autoantibodies were comprehensively checked during IIP diagnosis. Serum levels of CXCL10, CXCL1, CCL2, BAFF, angiopoietin-2, and leptin were evaluated at the time of IIP diagnosis.ResultsTwo hundred twenty-two patients (159 men and 63 women) with IIP were enrolled. The median observation duration was 36 months. The median age was 71 years old, and median %forced vital capacity (FVC) was 84.1% at the time of IIP diagnosis. The proportion of patients who met the classification criteria for IPAF was 11.7%. In patients with high serum CXCL10, changes in both %FVC and %diffusion lung capacity for carbon monoxide at one year were significantly higher than those in patients with low CXCL10 (p = 0.014 and p = 0.009, respectively), whereas these changes were not significant for other chemokines and cytokines. High CXCL10 levels were associated with acute/subacute onset (p < 0.001) and the diagnosis of nonspecific interstitial pneumonia with organizing pneumonia overlap (p = 0.003). High CXCL10 levels were related to a higher classification of IPAF (relative risk for IPAF was 3.320, 95%CI: 1.571–7.019, p = 0.003) and lower classification of progressive pulmonary fibrosis (PPF; relative risk for PPF was 0.309, 95%CI: 0.100-0.953, p = 0.027) compared to those with low CXCL10. Finally, survival was higher in patients with IPF and high CXCL10 (p = 0.044), and high CXCL10 was a significant prognostic factor in multivariate Cox proportional hazards models (hazard ratio 0.368, p = 0.005).ConclusionsHigh serum levels of CXCL10 are associated with CTD-related features, the favorable clinical course, and survival in patients with IIP, especially IPF.Clinical trial numberNot applicable.

A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease.

The inflammatory bowel diseases (IBD) known as Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract believed to arise because of an imbalance between the epithelial, immune and microbial systems. It has been shown that biological differences (genetic, epigenetic, microbial, environmental, etc.) exist between patients with IBD, with multiple risk factors been associated with disease susceptibility and IBD-related phenotypes (e.g. disease location). It is also known that there is heterogeneity in terms of response to therapy in patients with IBD, including to biological therapies that target very specific biological pathways (e.g. TNF-alpha signaling, IL-23R signaling, immune cell trafficking, etc.). It is hypothesized that the better the match between the biology targeted by these advanced therapies and the predominant disease-associated pathways at play in each patient will favor a beneficial response. The aim of this pilot study was to identify potential biological differences associated with differential treatment response to the anti α4β7 integrin therapy known as Vedolizumab. Our approach was to measure a broad range of analytes in the serum of patients prior to initiation of therapy and at the first clinical assessment visit, to identify potential markers of biological differences between patients at baseline and to see which biomarkers are most affected by treatment in responders. Our focus on early clinical response was to study the most proximal effects of therapy and to minimize confounders such as loss of response that occurs further distal to treatment initiation. Specifically, we performed targeted analyses of >150 proteins and metabolites, and untargeted analyses of >1100 lipid entities, in serum samples from 92 IBD patients (42 CD, 50 UC) immediately prior to initiation of therapy with vedolizumab (baseline samples) and at their first clinical assessment (14-week samples). We found lower levels of SDF-1a, but higher levels of PDGF-ββ, lactate, lysine, phenylalanine, branched chain amino acids, alanine, short/medium chain acylcarnitines, and triglycerides containing myristic acid in baseline serum samples of responders as compared to non-responders. We also observed an increase in serum levels of CXCL9 and citrate, as well as a decrease in IL-10, between baseline and week 14 samples. In addition, we observed that a group of metabolites and protein analytes was strongly associated with both treatment response and BMI status, although BMI status was not associated with treatment response.

Serum and Tissue CXCL9 Levels in Patients with Vitiligo Before and After Phototherapy: A Case-Control Study

Background: Vitiligo is a common pigmentation disease that affects 1–2% of the global population. It is a genetic disease that is triggered by an environmental factor resulting in an autoimmune disease. The predominance of the T-helper 1 (Th1) pattern favors the development of vitiligo. Interferon-gamma (IFN-γ) is the most important cytokine that is associated with the Th1 immune response. IFN-γ induces the release of chemokine which is called CXCL9. Objectives: Evaluation of the effects of narrow band ultraviolet B (nbUVB) phototherapy on the serum and tissue levels of CXCL9 among vitiligo patients. Patients and methods: We recruited in our study two groups; one group of twenty patients complaining of nonsegmental vitiligo and the other is a control group composed of another age and sex-matched twenty healthy controls, we assessed the serum level of CXCL9 in all subjects before the study and the patient group was reassessed after treatment with nbUVB for 12 weeks. We also determined tissue level of CXCL9 in patients before and after the phototherapy for 12 weeks from suction blister fluid. Results: We detected that serum levels of CXCL9 were higher in patients with vitiligo compared to healthy matched controls. nbUVB sessions for twelve weeks were done, and we found that serum and tissue levels of CXCL9 after treatment were decreased. Conclusion: Serum and tissue CXCL9 can be used as a marker for disease activity and potentiality for the response to treatment. Therefore, targeting the inhibition of the Interferon-γ-chemokine axis may help in treating the disease activity.

Candidate Biomarkers For Response To Treatment In Psoriatic Disease.

To determine whether biologic therapy alters serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in psoriatic arthritis (PsA) and psoriasis (PsC) patients, and whether baseline levels of these proteins predict response to treatment for PsA. We included PsA patients on TNF inhibitors (TNFi), Interleukin-17 inhibitors (IL-17i), methotrexate (MTX), and untreated with bDMARDs or csDMARDs (untreated) and PsC patients on bDMARDs and matched untreated. Serum samples at baseline and 3-6 months follow-up were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as: 1. Achieving low disease activity or remission (according to DAPSA), 2. 75% reduction in PASI, and 3. 50% reduction in actively inflamed joint count. In PsA, TNFi reduced serum levels of all five proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA (p<0.05). There were no significant differences between treated or untreated PsC patients. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (AUC>0.8) for response to biologics in PsA patients. Biologics treatment and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in PsA patients. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.

Endocrine immune-related adverse events by immune checkpoint inhibitors and potential predictive markers: a prospective study from a single tertiary center.

Immune checkpoint inhibitors (ICIs) can trigger immune-related adverse events (irAEs). The appearance pattern of irAEs, who is prone to them, and their mechanisms are still uncertain. In this study, we aimed to monitor patients initiated on ICIs for endocrinological aspects and to investigate the potential predictive markers in the development of endocrine-irAEs. The study prospectively included 43 patients with metastatic disease scheduled for anti-PD-1/L1 therapy. Endocrinological follow-up was conducted at specified intervals as well as in response to any additional reported complaints. Serum concentrations of CXCL10, IL-1beta, and IL-17A were measured prior to ICI and during the endocrine-irAEs. A total of 39.5% of the patients experienced endocrine-irAEs, with a median onset time of 3 months. Among patients, 34.9% developed thyroid-related adverse events, and 4.6% experienced hypophysitis. Thyroid autoantibodies were associated with a higher incidence of thyroid-related irAEs (P = 0.004). In the irAE group, median pre-ICI CXCL10 and baseline thyroid stimulating hormone (TSH) levels were significantly higher, baseline total testosterone level in men was lower than in the non-irAE group (P < 0.05), whereas IL-1beta and IL-17A levels did not differ (P > 0.05). Serum CXCL10, IL-1beta, and IL-17A concentrations did not differ significantly pre-ICI and during adverse events (P > 0.05). Pre-ICI CXCL10 concentration was correlated positively with anti-TPO levels in patients with at least one thyroid autoantibody positivity (r = 0.706, P = 0.01) and negatively with baseline total testosterone level of men (r = 0.509, P = 0.002). Our results suggest that higher pre-ICI serum CXCL10 and TSH levels might have a predictive role in the development of endocrinopathies. Besides, baseline thyroid antibody measurements could be beneficial in predicting thyroid dysfunction.

Effect of Follicular T Helper and T Helper 17 Cells-Related Molecules on Disease Severity in Patients with Myasthenia Gravis.

Contribution of T helper 1 and 2 cells-related cytokines to pathogenesis of myasthenia gravis (MG) is well known. Recently, the contribution of follicular T helper (Tfh) and T helper 17 cells-related molecules to the pathogenesis has gained importance. In this study, we aimed to evaluate the changes in Tfh- and Th17-related molecules before and after rescue therapy in patients with myasthenic crisis (cMG) and to reveal the molecular differences between stable MG and cMG patients. Patients with stable generalized MG (gMG) and cMG were classified according to Myasthenia Gravis Foundation of America (MGFA) classification. Serum samples were collected from cMG patients both before and after rescue therapy (plasmapheresis or intravenous immunoglobulin [IVIg]). Serum levels of Tfh- and selected Th17-related molecules (IL-22, IL-17A, CXCL13, sPD-L1, sICOSLG, and sCD40L) were analyzed by commercial ELISA kits. Twelve cMG (6 for IVIg, 6 for plasmapheresis) and 10 gMG patients were included in the study. A decrease in serum sPD-L1 and CXCL13 levels was observed in cMG patients after treatment, regardless of the treatment modality (p &lt; 0.05). In contrast, serum sICOSLG levels decreased only in patients treated with IVIg (p &lt; 0.05) and serum IL-22 levels increased in patients receiving plasmapheresis (p &lt; 0.05). cMG patients had higher serum IL-17A levels compared to stable patients (p &lt; 0.001) and its level was positively correlated with disease severity (r = 0.678, p = 0.001). Our results confirm the contribution of Tfh- and Th17-related cell pathways to MG pathogenesis. Both IVIg and plasmapheresis appear to be effective in reducing Tfh- and Th17-related cytokine/molecule levels in cMG patients. Increased serum IL-17A levels may contribute to disease severity.

Clinical significance of serum CXCL9, CXCL10, and CXCL11 in patients with lupus nephritis.

Lupus nephritis (LN) is an autoimmune disease as a complication of systemic lupus erythematosus (SLE). LN is typically diagnosed through a combination of clinical evaluation as index scoring, and kidney biopsy as a more accurate but invasive examination. In the current study, we assessed serological markers including IFN-γ-inducible chemokines C-X-C motif chemokine ligand (CXCL)9, CXCL10, and CXCL11 in diagnosing LN. A retrospective analysis was conducted on 160 SLE patients with and without LN. Fasting venous blood was collected from the study subjects for measuring serum levels of CXCL9, CXCL10, and CXCL11. The assessment of clinical disease activity in SLE was conducted using theSLE Disease Activity Index(SLEDAI)-2000 scoring system. LN disease activity was conducted using the Austin scoring system. LN was further confirmed following kidney biopsy, and data were compared by receiver operating characteristic(ROC) analysis. SLE patients with LN showed longer SLE duration, enhanced SLEDAI scores, lower serum anti-ds-DNA antibody levels when compared to SLE patients without LN. Specifically, these patients had significantly higher serum levels of CXCL9, CXCL10 and CXCL11. CXCL9, CXCL10, and CXCL11 showed positive correlation with SLE disease activity in SLE patients with LN. ROCanalysis of CXCL9, CXCL10, and CXCL11 showed substantial enhancement of sensitivity and specificity for the diagnosis of LN in the patients with SLE. Serum CXCL9, CXCL10, and CXCL11 levels may improve the sensitivity and specificity for the diagnosis of LN in SLE patients.

Ritlecitinib, a JAK3/TEC family kinase inhibitor, stabilizes active lesions and repigments stable lesions in vitiligo

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

Clinical significance of circulating biomarkers of immune-checkpoint molecules with atezolizumab plus bevacizumab therapy in unresectable hepatocellular carcinoma.

The aims of this study were to identify clinically significant biomarkers of a response to atezolizumab plus bevacizumab (ATZ + BV) therapy and to develop target strategies against unresectable hepatocellular carcinoma (u-HCC). We first investigated the potential of circulating tumor DNA (ctDNA) to serve as a biomarker for predicting the therapeutic outcome in 24 u-HCC patients treated with ATZ + BV therapy. Next, we analyzed levels of immune-related cytokines in blood samples from 134 u-HCC patients who received ATZ + BV. For this, serum immune-related molecules or cancer-immune cycle-related molecules that have been reported in HCC patient sera, namely CD274, LAG-3, CCL2, 4, 5, CXCL1, 9, 10, 12, 13, CX3CL1, CCR5, IFNγ and IL-6, 8 were measured using enzyme-linked immunosorbent assay. More than 1% of variant read frequency (VRF) mutations were found in TP53, APC, PIK3CA and VHL, although with no correlation with treatment response. Among the 15 cytokines evaluated, CXCL9 and LAG-3 levels were significantly different between patients with objective response (OR), stable disease (SD), and progressive disease (PD) following ATZ + BV treatment. Receiver-operating characteristic curve analyses of CXCL9 (cut-off value: 419.1pg/ml) and LAG-3 (cut-off value: 3736.3pg/ml) indicated areas of 0.779 and 0.697, respectively, for differentiating PD from non-PD and OR from non-OR. In multivariate analysis of progression-free survival (PFS) and overall survival (OS), high serum CXCL9 (hazard ratio (HR) and 95% confidence interval (CI): 0.412 (0.251-0.677) (p = 0.0005) for PFS and 0.252 (0.125-0.508) (p = 0.0001) for OS), and low serum LAG-3 (HR and 95% CI 0.419 (0.249-0.705) (p = 0.0011) for PFS and 0.294 (0.140-0.617) (p = 0.0012) for OS) were independent positive predictive factors. Although, as far as we examined, no ctDNA mutations in blood were found to be related to ATZ + BV treatment efficacy, serum CXCL9 and LAG-3 levels, which are related to the cancer-immune cycle, were associated with treatment efficacy and could be predictive markers of the efficacy of ATZ + BV treatment in HCC patients.

Serum Levels of CXCL10 in Patients with Lupus Nephritis and its Relation with Disease Activity

Abstract Objective To evaluate the levels of CXCL10 in lupus nephritis (LN) patients and its relation with the activity of lupus nephritis. Patients and Methods Thirty four lupus patients were enrolled in our study, 17patients had lupus nephritis (LN) and 17 patients were without evidence of had lupus nephritis (LWN). Seventeen healthy subjects were also participated as a control group. Complete biochemical and serological parameters were measured and their correlation with serum levels of CXCL10 were assessed in the studied groups. Results The mean age of the LN patients was 31.94 ± 6.37,the mean age of LWN patient was 31.11± 6.42 and the mean age of the controls was 30.471± 4.705, Serum levels of CXCL10 were significantly elevated in LN patients group than LWN and control group with p-value &amp;lt;0.001,While serum CXCL10 in LWN was statistically increased than control group with p-value&amp;lt;0.001. Based on the receiver operator characteristic (ROC) curve analysis the efficacy of Serum CXCL10 levels in LN in a sample of Egyptian SLE patient This biomarker may be useful due to its high accuracy, with a sensitivity 94.12% and specificity of 76.47% as a biomarker of nephritis in SLE. There were statistically significant positive correlations between CXCL10 and 24 urinary protein (p-value = 0.031) (r = 0.524), creatinine (p-value = 0.003) (r = 0.682), renal activity (RSLEDAI) (p-value = 0.013) (r = 0.590) and Activity index (p-value = 0.003) (r = 0.669), whereas there was negative correlations between them and C3 (p-value = 0.021) (r=-0.554). Conclusion Being higher in patients with LN, CXCL10 might play a role in the pathogenesis of the disease. In addition to its excellent diagnostic performance for discriminating patients with lupus nephritis from other SLE patients, it might be helpful to predict the onset and progression of lupus nephritis in SLE patients and to detect renal flares.

Role of CXCL-10 as a Biomarker for Rheumatoid Arthritis

Abstract Background CXCL-10 has been detected within sera, synovial fluid, and synovial tissue in patients with RA and identified as a pro-inflammatory chemokine that mediate leukocyte trafficking and modulate innate and adaptive immune responses. It plays a critical role in the inflammatory response and is involved in several biological processes. Objective To evaluate the predicative significance of chemokine CXCL10 in rheumatoid arthritis (RA) and to focus on its relation to disease activity. Patients and Methods A case control study included 30 patients; were diagnosed with RA, and 30 healthy controls. Clinical examination was done for all patients. Measurement of serum CXCL10 level was done by ELISA, while assessment of disease activity in patients was done using disease activity score (DAS-28). Serum levels of CXCL10 were significantly higher in RA patients than controls. Results Serum level of CXCL-10 was ranging from 349–1380 pg/ml with a mean of 784.6 ± 152.2 in RA patients, which was very high level compared to control group the serum level was ranging from 137 – 476.8 pg/ml with a mean of 338.1 ± 125.5. The difference was statistically highly significant (p &amp;lt; 0.001). AUC for CXCL-10 was 0.951 and the 95% CI was ≤ 1. The cutoff point of CXCL-10 was 450 pg/mL were able to differentiate between RA patients and control group. Most of RA patients (70%) were on methotrexate with dose ranged from 12.5–25 mg per week. Thirty-five (58.3%) patients were on steroids with dose 5-20 mg per day. Comparison of CXCL-10 levels in patients with different grades of disease activity had a statistically significant difference between different grades. Conclusion Our study supports the critical role of CXCL10 in the RA inflammatory cascade. The correlation of CXCL10 with clinical disease activity suggests that CXCL10 plays a central role in RA inflammation and may serve as a disease activity marker in RA. CXCL10 has a significant role as a biomarker for prediction of RA.

Differential expression of serum CXCL9 and CXCL10 levels in vitiligo patients and their correlation with disease severity and stability: A cross-sectional study.

Background Vitiligo is an acquired disorder of pigmentation with an elusive pathogenesis, though various theories have been proposed. The presence of peri-lesional autoreactive CD8+ T cell infiltrate suggests the involvement of abnormal immune responses and autoimmunity in vitiligo. Recent studies have identified the IFN-γ-CXCL9/CXCL-10 axis as a key component of the autoimmune response that perpetuates disease activity in vitiligo. Objectives The primary objective was to estimate serum CXCL9 and CXCL10 levels in vitiligo patients compared to age- and sex-matched controls. Additionally, the study aimed to find correlations between CXCL9 and CXCL10 levels and disease severity and stability. Secondary objectives included comparing levels in segmental/nonsegmental vitiligo and stable/progressive vitiligo and assessing the impact of age and gender. Methods A hospital-based cross-sectional study included 60 vitiligo patients and 30 age- and sex-matched controls. Serum levels of CXCL9 and CXCL10 were assessed using Enzyme-linked immunosorbent assay (ELISA). Cases were clinically evaluated for the type of vitiligo (segmental or non-segmental), disease severity (VASI score), and disease stability (VIDA score). Statistical analysis included t-tests, chi-square tests, and correlation coefficients. P value less than 0.5 was taken as significant. Results Serum CXCL9 and CXCL10, both, were significantly raised in vitiligo patients as compared to controls (p-value = 0.001* & 0.001* respectively) and correlated positively with both VASI score (p-value = 0.001* & 0.001* respectively) and with VIDA score (p-value = 0.032* & 0.001* respectively). Serum CXCL10 showed significant elevation in progressive vitiligo, and CXCL9 exhibited a non-significant trend. No significant difference was observed between segmental and non-segmental vitiligo. Both chemokines positively correlated with disease severity and stability, while age and gender did not significantly impact chemokine levels. Conclusion The expression of chemokines CXCL9 and CXCL10 is markedly increased and correlated positively with disease severity & instability, underscoring their mechanistic role in vitiligo pathogenesis. The values were also higher in the progressive group than in the stable group, inferring their conceivable potential as serum biomarkers. Both serum CXCL9 and CXCL10 were significantly elevated in vitiligo patients compared to controls and they can be used as potential serum biomarkers for assessing the disease activity. Limitations Small sample size of control population. The voluntary sampling technique led to an unequal number of patients in progressive and stable vitiligo groups, as well as in segmental and non-segmental groups. The current study did not include blister fluid analysis and the effect of therapy on the chemokine levels. Conclusion The expression of chemokines CXCL9 and CXCL10 is markedly increased and correlates positively with disease severity and instability, underscoring their mechanistic role in vitiligo pathogenesis. The values were also higher in the progressive group than in the stable group, inferring their conceivable potential as serum biomarkers. *represents statistically significant results.

Distinct inflammatory markers in primary and secondary dengue infection: can cytokines CXCL5, CXCL9, and CCL17 act as surrogate markers?

ABSTRACT Dengue fever poses a significant global health threat, with symptoms including dengue hemorrhagic fever and dengue shock syndrome. Each year, India experiences fatal dengue outbreaks with severe manifestations. The primary cause of severe inflammatory responses in dengue is a cytokine storm. Individuals with a secondary dengue infection of a different serotype face an increased risk of complications due to antibody-dependent enhancement. Therefore, it is crucial to identify potential risk factors and biomarkers for effective disease management. In the current study, we assessed the prevalence of dengue infection in and around Aligarh, India, and explored the role of cytokines, including CXCL5, CXCL9, and CCL17, in primary and secondary dengue infections, correlating them with various clinical indices. Among 1,500 suspected cases, 367 tested positive for dengue using Real-Time PCR and ELISA. In secondary dengue infections, the serum levels of CXCL5, CXCL9, and CCL17 were significantly higher than in primary infections (P < 0.05). Dengue virus (DENV)-2 showed the highest concentrations of CXCL5 and CCL17, whereas DENV-1 showed the highest concentrations of CXCL9. Early detection of these cytokines could serve as potential biomarkers for diagnosing severe dengue, and downregulation of these cytokines may prove beneficial for the treatment of severe dengue infections.

Meta-analyses of the relationship between five CXCL8 gene polymorphisms and overall cancer risk, and a case-control study of oral cancer

BackgroundC-X-C motif chemokine ligand (CXCL8), also known as interleukin-8, is a prototypical CXC family chemokine bearing a glutamic acid-leucine-arginine (ELR) motif that plays key roles in the onset and progression of a range of cancers in humans. Many prior studies have focused on exploring the relationship between CXCL8 gene polymorphisms and the risk of cancer. However, the statistical power of many of these reports was limited, yielding ambiguous or conflicting results in many cases.MethodsAccordingly, the PubMed, Wanfang, Scopus and Web of Science databases were searched for articles published until July 20, 2023 using the keywords ‘IL-8’ or ‘interleukin-8’ or ‘CXCL8’, ‘polymorphism’ and ‘cancer’ or ‘tumor’. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to examine the association. The CXCL8 +781 polymorphism genotypes were assessed with a TaqMan assay.ResultsAbout 29 related publications was conducted in an effort to better understand the association between these polymorphisms and disease risk. The CXCL8 -353A/T polymorphism was associated with an increased overall cancer risk [A vs. T, odds ratio (OR) = 1.255, 95% confidence interval (CI) (1.079–1.459), Pheterogeneity = 0.449, P = 0.003]. The CXCL8 +781 T/C allele was similarly associated with a higher risk of cancer among Caucasians [TT vs. TC + CC, OR = 1.320, 95%CI (1.046–1.666), Pheterogeneity = 0.375, P = 0.019]. Furthermore, oral cancer patients carrying the CXCL8 +781 TT + TC genotypes exhibited pronounced increases in serum levels of CXCL8 as compared to the CC genotype (P < 0.01), and also shown similar trend as compared to genotype-matched normal controls (P < 0.01). Finally, several limitations, such as the potential for publication bias or heterogeneity among the included studies should be paid attention.ConclusionCurrent study suggested that the CXCL8 -353 and +781 polymorphisms may be associated with a greater risk of cancer, which might impact cancer prevention, diagnosis, or treatment through the different expression of CXCL8. At the same time, the +781 polymorphism may further offer value as a biomarker that can aid in the early identification and prognostic evaluation of oral cancer.

CXCL10 regulates pressure overload-induced heart failure

Rationale: Heart failure involves tissue inflammation with elevated serum levels of CXCL9 and CXCL10, which are CXCR3 receptor ligands. Both chemokines are expressed by cardiac fibroblasts and myeloid cells in mice subjected to pressure overload induced by transverse aortic constriction (TAC) surgery. Although it is known that CXCR3−/− animals are protected from cardiac remodeling induced by TAC, the role of CXCL10 is unknown. The present study was undertaken to test the hypothesis that CXCL10 is crucial in the cardiac remodeling response to pressure overload induced by TAC in mice. Methods: We subjected wild-type and CXCL10−/− mice to TAC surgery, resulting in 4 experimental groups: WT Sham, WT TAC, CXCL10−/− Sham and CXCL10−/− TAC. WGA was used to analyze the cross-sectional area of cardiomyocytes. To analyze total collagen deposition, PicroSirius Red was used. Immunohistochemistry was performed to measure the number of CD64, CD3g and CD45 positive cells. Echocardiography was used to analyze cardiac function. Results are presented as the mean and standard error of the mean. Comparisons between means were made using two-way variance analysis (ANOVA), as well as Tukey's post hoc test for parametric comparisons, or Kruskal-Wallis and Dunn‘s post hoc test for non-parametric data. Differences with p&lt;0.05 were considered significant. Results: After 1 week, the CXCL10−/− mice showed the same level of cardiac hypertrophy and similar changes in echocardiography parameters, when compared to wild-type mice. However, after 6 weeks, we observed that the CXCL10−/− mice showed an attenuation of heart weight with a reduction in the total collagen deposition compared with wild-type TAC mice. At the cellular level, the genetic deletion of CXCL10 prevented the TAC-induced increase in the cross-sectional area of cardiomyocytes. Moreover, we observed that TAC increased the number of CD3+ T-cells in the heart quantified from stained cross sections of both wild type and CXCL10−/− mice, while no differences were observed for the total number of macrophages. Importantly, echocardiographic changes, including dilation and cardiac dysfunction, induced by pressure overload in wild animals were blunted in CXCL10−/− mice. Corroborating this, the genetic deletion of CXCL10 prevented the increase in lung weight induced by TAC. Conclusion: CXCL10 regulates cardiac hypertrophy and fibrosis induced by pressure overload in mice, as well as the functional changes that characterize heart failure. We are currently unraveling the mechanism through which CXCL10 can accelerate the development of heart failure in response to cardiac pressure overload. Interaction between T cells and macrophages are likely mediating these effects. R01HL155993. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

CXCL9 Overexpression Predicts Better HCC Response to Anti-PD-1 Therapy and Promotes N1 Polarization of Neutrophils.

Anti-programmed death-1 (PD1) antibodies have changed the treatment landscape for hepatocellular carcinoma (HCC) and exhibit promising treatment efficacy. However, the majority of HCCs still do not respond to anti-PD-1 therapy. We analyzed the expression of CXCL9 in blood samples from patients who received anti-PD-1 therapy and evaluated its correlation with clinicopathological characteristics and treatment outcomes. Based on the results of Cox regression analysis, a nomogram was established for predicting HCC response to anti-PD-1 therapy. qRT‒PCR and multiple immunofluorescence assays were utilized to analyze the proportions of N1-type neutrophils in vitro and in tumor samples, respectively. The nomogram showed good predictive efficacy in the training and validation cohorts and may be useful for guiding clinical treatment of HCC patients. We also found that HCC cell-derived CXCL9 promoted N1 polarization of neutrophils in vitro and that AMG487, a specific CXCR3 inhibitor, significantly blocked this process. Moreover, multiple immunofluorescence (mIF) showed that patients with higher serum CXCL9 levels had greater infiltration of the N1 phenotype of tumor-associated neutrophils (TANs). Our study highlights the critical role of CXCL9 as an effective biomarker of immunotherapy efficacy and in promoting the polarization of N1-type neutrophils; thus, targeting the CXCL9-CXCR3 axis could represent a novel pharmaceutical strategy to enhance immunotherapy for HCC.