Serum Concentrations Of CXCL10 Research Articles

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.

Investigating Association Level of CXCL12 with its SDF-1α 3'A Genetic Variant and CXCL10 with its 1443 Promoter Polymorphism in Type-1 Diabetes.

Type-1 Diabetes Mellitus (T1DM) is an autoimmune and heterogeneous disorder. In the present study, we aimed to examine whether there exists an association between serum CXCL10 (IP-10) level and its promoter polymorphism at position-1443 along with CXCL12 and its known SDF-1 3' A genetic variant as an angiogenesis chemokine in T1DM patients. Blood specimens were collected from 209 unrelated T1DM patients and 189 healthy subjects. The DNA samples were extracted from the subjects and analyzed for CXCL10 and CXCL12 polymorphisms using PCR-RLFP. The serum concentrations of CXCL10 and CXCL12 were also analyzed with ELISA. Following expert opinion and data analysis, we found significant differences between A/A, A/G, and G/G genotypes with A and G alleles of polymorphisms at position +801 (SDF-1α3'A) in CXCL12. No association was reported between CXCL10/-1443 promoter polymorphism and T1DM. In our assessment of promoter polymorphism, both T1DM patients and controls had GG genotypes in CXCL10/-1443. When patients were compared with controls, both serum CXCL10 and CXCL12 levels were found to be increased in type 1 diabetes with complications. Levels were not increased in patients without complications. Both CXCL10 and CXCL12 play fundamental roles in T1DM pathogenesis. Only the CXCL12 3'A (SDF-1α3'A) polymorphism is possibly necessary for the pathogenesis of T1DM, while the CXCL10-1443 promoter polymorphism is not.

CMP-001-007: Open-label, phase 2 study of intratumoral CMP-001 + pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma.

TPS6089 Background: PD-1 blockade ± chemotherapy has recently become a primary systemic therapy recommended by NCCN guidelines for patients (pts) with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, most pts still do not respond to treatment, indicating a large unmet need for pts with unresectable disease. CMP-001 is a toll-like receptor 9 (TLR9) agonist comprising a CpG-A oligodeoxynucleotide packaged in a virus-like particle that can induce type I interferon secretion from tumor-associated plasmacytoid dendritic cells, promoting a Th1-like chemokine milieu in the tumor microenvironment and inducing an antitumor CD8+ T-cell response. In a phase (ph) 1b study in pts with metastatic melanoma, intratumoral (IT) injection of CMP-001 + intravenous (IV) pembrolizumab (pembro) reversed PD-1 blockade resistance, induced responses in injected and noninjected lesions, and had an acceptable safety profile (Milhem et al, SITC 2020). This combination is therefore being tested in pts with HNSCC. Methods: CMP-001-007 (NCT04633278) is an open-label, multicenter, ph 2 study designed to investigate the efficacy and safety of CMP-001 + IV pembro in adult pts with histologically or cytologically confirmed R/M HNSCC considered incurable by local therapies. Eligible pts have undergone a pretreatment tumor biopsy, received no prior systemic therapy in the R/M setting, and have primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. In addition, pts must have PD-L1-positive tumors (combined positive score ≥1), known tumor human papillomavirus (HPV) status (for oropharyngeal cancer), and measurable disease per RECIST v1.1 with ≥1 lesion amenable to IT injection. Pts with primary tumors in the nasopharynx are excluded. Enrolled pts will receive CMP-001 10 mg once weekly for 7 doses and every 3 weeks (Q3W) thereafter. The first dose may be administered subcutaneously or via IT injection, with all subsequent doses administered IT. All pts will also receive pembro 200 mg IV Q3W after the CMP-001 injection. Treatment continues until unacceptable toxicity or disease progression. The primary endpoint is investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints include safety, duration of response (DOR), progression-free survival (PFS), overall survival, and effects of HPV infection and PD-L1 expression on ORR, DOR, and PFS. Exploratory endpoints include analyses of baseline and changes from baseline in tumor or serum biomarkers related to TLR9, immune checkpoints, and potential predictors of response, as well as serum concentrations of CXCL10 and CMP-001. Refer to clinicaltrials.gov/ct2/show/NCT04633278 for the most current information on enrolling sites. Clinical trial information: NCT04633278.

Responsiveness to oral prednisolone in severe asthma is related to the degree of eosinophilic airway inflammation.

Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear. To relate the physiological and inflammatory response to systemic corticosteroids in asthma to disease severity and the baseline extent of eosinophilic inflammation. Patients with mild/moderate and severe asthma were investigated before and after 2 weeks of oral prednisolone (Clintrials.gov NCT00331058 and NCT00327197). We pooled the results from two studies with common protocols. The US study contained two independent centres and the UK one independent centre. The effect of oral corticosteroids on FEV1 , Pc20, airway inflammation and serum cytokines was investigated. Baseline measurements were compared with healthy subjects. Thirty-two mild/moderate asthmatics, 50 severe asthmatics and 35 healthy subjects took part. At baseline, both groups of asthmatics had a lower FEV1 and Pc20 and increased eosinophilic inflammation compared to healthy subjects. The severe group had a lower FEV1 and more eosinophilic inflammation compared to mild/moderate asthmatics. Oral prednisolone caused a similar degree of suppression of eosinophilic inflammation in all compartments in both groups of asthmatics. There were small improvements in FEV1 and Pc20 for both mild/ moderate and severe asthmatics with a correlation between the baseline eosinophilic inflammation and the change in FEV1 . There was a ~50% reduction in the serum concentration of CXCL10 (IP-10), CCL22 (MDC), CCL17 (TARC), CCL-2 (MCP-1) and CCL-13 (MCP-4) in both asthma groups after oral corticosteroids. Disease severity does not influence the response to systemic corticosteroids. The study does not therefore support the concept that severe asthma is associated with corticosteroid resistance. Only baseline eosinophilic inflammation was associated with the physiological response to corticosteroids, confirming the importance of measuring eosinophilic inflammation to guide corticosteroid use.

The Chemokine CXCL-10 Is a Marker of Infection Stage in Individuals With DNAemia Due to Parvovirus B19.

Accurate diagnosis of parvovirus B19 (B19V) infection requires the differentiation between acute and past infection, which is especially important when DNAemia due to B19V (hereafter, "B19V DNAemia") is detected in pregnancy. Here, we explored whether the level of the chemokine CXCL-10, in combination with findings of molecular and serological assays, can discriminate between acute and past B19V infection. B19V DNA-positive serum samples from 222 immunocompetent individuals were analyzed for (1) viral DNA loads, (2) anti-B19V immunoglobulin M (IgM) and immunoglobulin G (IgG), (3) anti-VP1 IgG avidity, (4) anti-VP-2 epitope type specificity (ETS), and (5) CXCL-10 serum levels. Anti-B19V IgM and IgG, avidity, and ETS assays were used to categorize individuals with B19V DNAemia as having acute or past B19V infection. Acute B19V infection caused a significant increase in the serum concentration of CXCL-10, compared with the concentration at baseline, before infection. Higher CXCL-10 serum levels were furthermore detected in acute B19V infection as compared to past infection. As a marker, CXCL-10 serum levels could discriminate between acute and past B19V infection, with an excellent discriminatory capacity when CXCL-10 and B19V DNA levels were used as combined parameters. Acute B19V infection is associated with increased CXCL-10 production, and measurement of CXCL-10 serum levels thus allows for the staging of B19V infection in individuals with B19V DNAemia.

Antibodies recognizing specific Mycobacterium avium subsp. paratuberculosis’s MAP3738c protein in type 1 diabetes mellitus children are associated with serum Th1 (CXCL10) chemokine

Recently Mycobacterium avium subsp. paratuberculosis (Map) was associated to type 1 diabetes mellitus (T1DM). In this study we investigated for Map presence in children affected by T1DM compared to healthy children. A pool of 212 sera from T1DM children at onset was compared to sera from 57 healthy children for humoral immune response towards the Map specific protein MAP3738c by ELISA. Serum concentrations of CXCL10 (pro-Th1) and CCL2 (pro-Th2) chemokines were also measured in both sera pool. Results showed that T1DM children had a stronger seropositivity towards MAP3738c protein compared to healthy children. Data highlighted also the correlation between serum activity of T1DM patients towards the specific protein of Map and the increase of CXCL10 concentration if compared to non-diabetic subjects. In conclusion, an immune response to Map in T1DM patients at onset was observed and this may indicate a role of the bacterium in triggering or precipitating the disease.

CXCL10 Activities, Biological Structure, and Source Along with Its Significant Role Played in Pathophysiology of Type I Diabetes Mellitus

The etiology of the most autoimmune disorders is largely yet to be understood. However, major target antigens have been determined against some of clinically important molecules of human autoimmune diseases, such as insulin in type 1 diabetes mellitus (T1DM). T1DM is believed to be resulted from immune-mediated destruction of insulin-producing β-cells in pancreatic islets of Langerhans. Chemokines are small glycoproteins (weighing 8-10kDa) that are chemotactive for a wide variety of cell types especially immune system cells and their target cells express appropriate G protein receptors. CXCL10 is a 10-kDa protein and is functionally categorized as an "inflammatory" chemokine. Recently, accumulating reports have shown that the serum and/or the tissue expressions of CXCL10 are increased in various autoimmune diseases like T1DM. Thus, in this article we will focus on the crucial role(s) played by CXCL10 in pathogenesis of T1DM. Therefore, we tried our best to collect the current reports regarding relationship between the serum concentrations of CXCL10 in T1DM.