Cytokine Profiles In Peripheral Blood Research Articles

Assessing molecular genetic and immunological predictors of COVID-19 course in healthcare worker risk group

Relevance. Studying features of innate and adaptive mechanisms of immune response in medical workers (MW), the most vulnerable social group with a high risk of infection, is an urgent research task. The aim of the study: Comprehensive study of innate and adaptive immune mechanisms and analyzing relationships between clinically significant polymorphisms (SNPs) in TLR2, TLR4 genes, TLR2 expression level on peripheral blood monocytes, peripheral blood cytokine profile (IL-1β, IL-10, IL-6, IFNγ, platelet activation marker) and SARS-CoV-2-specific humoral immune response in medical workers (MW) at a temporary infectious disease hospital in early and late COVID-19 convalescence. Materials and methods. immunologic, cytofluorimetric and molecular-genetic research methods were applied. Adaptive immune response in medical workers — COVID-19 convalescent subjects. Results. Early post-COVID-19 convalescence period in MW was linked to higher TLR2 monocyte expression; the mean fluorescence intensity was significantly elevated by 1.5-fold compared to control group. Late convalescence period (7 months post-COVID-19) was characterized by lowered serum IFNγ level. A decline in IFNγ production was significant: decreased by 82-fold in MR that was markedly stronger compared to control group (59 times). The imbalance of cytokines controlling antiviral innate and adaptive immune response was revealed in MW with identified combination of polymorphisms rs5743708 and rs4986790 in TLR2, TLR4 genes with the rate not exceeding 6.7%. It was found that 7 months after COVID-19 there was a markedly decreased IFNγ, IL-1β and IL-10 levels. The studies indicate both altered innate and adaptive immune mechanisms and a need to optimize therapeutic and prophylactic measures aimed at increasing patient-intrinsic resistance, protection of respiratory tract mucosal barriers and identification of genetic predictors of defects in innate and adaptive immune response in medical workers — COVID-19 convalescent subjects.

Effect of antiviral and immunomodulatory treatment on a cytokine profile in patients with COVID-19.

The severity of COVID-19 is associated with an elevated level of a variety of inflammatory mediators. Increasing evidence suggests that the Th17 response contributes to the severity of COVID-19 pneumonia, whereas Th22 response plays a regulatory role in SARS-CoV-2 infection. Two main types of available COVID-19 treatments are antivirals and immunomodulatory drugs; however, their effect on a cytokine profile is yet to be determined. This study aim to analyse a cytokine profile in peripheral blood from patients with COVID-19 (n=44) undergoing antiviral or/and immunomodulatory treatment and healthy controls (n=20). Circulating CD4+ and CD8+ T cells and their intracellular expression of IL-17A and IL-22 were assessed by flow cytometry. Initial results showed an overexpression of IL-17F, IL-17A, CCL5/RANTES, GM-CSF, IL-4, IL-10, CXCL-10/IP-10 and IL-6 in COVID-19 patients compared to healthy controls. Treatment with remdesivir resulted in a significant decline in concentrations of IL-6, IL-10, IFN-alpha and CXCL10/IP-10. Immunomodulatory treatment contributed to a significant downregulation of IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 as well as upregulation of IL-22 and IL-1 beta. A combination of an antiviral and immunomodulatory treatment resulted in a significant decrease in IL-17F, IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 levels as well as an increase in IL-17A and IL-1 beta. We found significantly higher percentage of both CD4+ and CD8+ T cells producing IL-17A and CD4+ T cells producing IL-22 in patients with COVID-19. Administration of antiviral or/and immunomodulatory treatment resulted in a significant downregulation of pro-inflammatory cytokine expression and an upregulation of T cell absolute counts in most cases, thus showing effectiveness of treatment in COVID-19. SARS-CoV-2 infection induced cytokine overexpression in hospitalized patients with COVID-19 as well as lymphopenia, particularly a decrease in CD4+ and CD8+ T cell counts. Moreover, despite the reduced counts of CD4+ and CD8+ T cells, both subsets showed overactivation and increased expression of IL-17A and IL-22, thus targeting Th17 response might alleviate inflammatory response in severe disease.

WIN Symposium 2022 - Abstract Poster Presentations.

WIN Symposium 2022 - Abstract Poster Presentations.

O-224 Novel bio-markers of Immunological response to the implanting embryo

Abstract Embryos, as allograft, will fail to implant unless they can escape rejection by maternal immune response. It is postulated that embryos escape Immune surveillance using a mechanism similar to that of cancer cells via Immune check point pathways: (a) via producing a surface protein called PD-L1, which binds to PD-1 receptor in T-cells; and (b) via producing a surface protein called Galectin-9 which binds to T-cell immunoglobulin and mucin domain 3 (TIM-3). The binding of these ligands to the corresponding receptors in the T-cells would prevent the latter from recognizing them as foreign, hence escape destruction. In a prospective, longitudinal, observational cohort study involving subjects undergoing blastocyst transfer, it was found that among women who conceived, there was an instant, transient and significant reduction of Tim-3 expression on the surface of peripheral NK cells, T cells and NK-like T cells on days 3 and 6 after ET, which returned to baseline level by day 9 after ET. The change in women who did not conceive appeared in an opposite direction. Furthermore, reduction in Tim-3 expression in pNK cells predates the occurrence of miscarriage by 3 weeks in women with miscarriage when compared with those with live birth. These observations are accompanied by significant changes in peripheral blood cytokine profiles which may be used as clinically useful biomarkers to monitor the maternal immunological response to successful implantation.

Cytokine profile in peripheral blood of patients with metastatic colorectal cancer with different responses to chemotherapy in combination with anti-VEGF agents.

e15545 Background: For many years, colorectal cancer has been among the most frequently diagnosed cancers and one of the leading causes of cancer death. The effect of monoclonal antibodies on the immunological status remains relevant, since chemotherapy in combination with monoclonal antibodies (anti-EGFR, anti-VEGF) plays a key role in the treatment of patients with metastatic colorectal cancer. The purpose of this study was to reveal specific features of the cytokine profile of patients with metastatic colorectal cancer (mCRC) receiving bevacizumab in combination with chemotherapy before and after the treatment. Methods: The study included 15 patients with newly diagnosed mCRC receiving mFOLFOX6 chemotherapy combined with bevacizumab as the first-line treatment. Cytokine levels were determined in the blood serum (BS) by multiplex assay with the Bio-Plex Pro Human Immunotherapy 20-Plex Panel (GM-CSF, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL-15, IL-17A, IL-18, IP-10, MCP-1, MIG, MIP-1α, MIP-1β, RANTES, TNF-α) (Bio-Rad, USA) before and after 4 cycles of the therapy. Results were evaluated using the Luminex 200 Analyzer (Bio-Rad, USA) with the Bio-Plex Manager Software. Results: Complete response to the therapy was registered in 5 (33.3%) patients, partial remission in 8 (53.3%) patients, progression in 13.3%. IL-6, IP-10, MIG, RANTES, and TNF-a were statistically significantly (p < 0.05) elevated in patients with complete response. IL-8 showed a tendency to decreasing after the therapy. Levels of IL-6, IL-8, IL-15, IL-17, and MIP-1a in patients with partial remission after the therapy reduced to zero values. An analysis of the cytokine profiles in patients with progression demonstrated a decrease of all the studied indices, except for elevated IL-15 and IL-17. Conclusions: Anti-VEGF agents together with chemotherapy changed the cytokine profiles in patients with mCRC. Probable mechanism may include the implementation of the antitumor response through the activation of some pro-inflammatory cytokines, since the complete response was accompanied by an increase in IL-6, IP-10, MIG, RANTES, TNF-a and a decrease in IL8.

Increased Frequency of CD4+ Follicular Helper T and CD8+ Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis.

Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody-positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Subsequently, we confirmed their presence in lymph nodes and synovial tissue of RA patients using immunofluorescence microscopy. In the blood, the frequency of Tfh cells did not differ between study groups. In lymphoid and synovial tissues, Tfh cells were localized in B-cell areas, and their frequency correlated with the frequency of CD19+ B cells. Compared to lymphoid tissues of healthy controls, those of RA patients and RA-risk individuals showed more CD19+ B cells, CD4+CXCR5+ follicular helper T cells, and CD8+CXCR5+ follicular T cells. These Tfh cells produced less IL-21 upon ex vivo stimulation. These findings suggest that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of RA to prevent further disease progression.

Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings.

Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of graft dysfunction. Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels. This patient subset was hallmarked by a high prevalence (75%) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) and histological rejection (70%) and had worse graft survival compared to the group with low cytokine levels (HLA-DSA in 1.7% and rejection in 33.7%). Thirty percent of patients with high pro-inflammatory cytokine levels and HLA-DSA did not have histological rejection. Exploring the cellular origin of these cytokines, we found a corresponding expression in endothelial cells, monocytes, and natural killer cells in single-cell RNASeq data from kidney transplant biopsies. Finally, we confirmed secretion of these cytokines in HLA-DSA-mediated cross talk between endothelial cells, NK cells, and monocytes. In conclusion, blood pro-inflammatory cytokines are increased in kidney transplant patients with HLA-DSA, even in the absence of histology of rejection. These observations challenge the concept that histology is the gold standard for identification of ongoing allo-immune activation after transplantation.

Defective Interferon-Gamma Production Is Common in Chronic Pulmonary Aspergillosis.

Immune defects in chronic pulmonary aspergillosis (CPA) are poorly characterized. We compared peripheral blood cytokine profiles in patients with CPA versus healthy controls and explored the relationship with disease severity. Interferon-gamma (IFNγ), interleukin (IL)-17, tumor necrosis factor-α, IL-6, IL-12, and IL-10 were measured after in vitro stimulation of whole blood with lipopolysaccharide (LPS), phytohemagglutinin, β-glucan, zymosan (ZYM), IL-12 or IL-18, and combinations. Clinical parameters and mortality were correlated with cytokine production. Cytokine profiles were evaluated in 133 patients (57.1% male, mean age 61 years). In comparison to controls, patients with CPA had significantly reduced production of IFNγ in response to stimulation with β-glucan + IL-12 (312 vs 988 pg/mL), LPS + IL-12 (252 vs 1033 pg/mL), ZYM + IL-12 (996 vs 2347 pg/mL), and IL-18 + IL-12 (7193 vs 12330 pg/mL). Age >60 (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.00-2.91; P = .05) and chronic obstructive pulmonary disease (HR, 1.69; 95% CI, 1.03-2.78; P = .039) were associated with worse survival, whereas high IFNγ production in response to beta-glucan + IL-12 stimulation (HR, 0.48; 95% CI, .25-0.92; P = .026) was associated with reduced mortality. Patients with CPA show impaired IFNγ production in peripheral blood in response to stimuli. Defective IFNγ production ability correlates with worse outcomes. Immunotherapy with IFNγ could be beneficial for patients showing impaired IFNγ production in CPA.

Identification of Immune Activation Markers in the Early Onset of COVID-19 Infection.

This study aimed to determine the specific cytokine profile in peripheral blood during the early onset of COVID-19 infection. This was a cross-sectional exploratory, single center study. A total of 55 plasma samples were studied. Serum samples of adults showing symptoms of COVID-19 infection who were tested positive for SARS-CoV-2 infection (CoV+, n=18) at the COVID-19 outpatient clinic of the Medical University of Vienna were screened for immune activation markers by Luminex technology. Additionally, age and gender-matched serum samples of patients displaying COVID-19 associated symptoms, but tested negative for SARS-CoV-2 (CoV-, n=16) as well as healthy controls (HC, n=21) were analyzed. COVID-19 positive (CoV+) patients showed a specific upregulation of BLC (141; 74-189 pg/mL), SCD30 (273; 207-576 pg/mL), MCP-2 (18; 12-30 pg/mL) and IP-10 (37; 23-96 pg/mL), compared to patients with COVID19-like symptoms but negative PCR test (CoV-), BLC (61; 22-100 pg/mL), sCD30L (161; 120-210 pg/mL), MCP-2 (8; 5-12 pg/mL) and IP-10 (9; 6-12 pg/mL) and healthy controls (HC) (BLC 22; 11-36 pg/mL, sCD30 74; 39-108 pg/mL, MCP-2 6; 3-9. pg/mL, IP-10 = 8; 5-13). The markers APRIL, sIL-2R, IL7, MIF, MIP-1b, SCF, SDF-1a, sTNF-RII were elevated in both CoV+ and CoV- patient groups compared to healthy controls. HGF, MDC and VEGF-A were elevated in CoV- but not CoV+ compared to healthy controls. BLC, sCD30, MCP-2 and IP-10 are specifically induced during early stages of COVID-19 infection and might constitute attractive targets for early diagnosis and treatment of this disease.

Cytokine Consistency Between Bone Marrow and Peripheral Blood in Patients With Philadelphia-Negative Myeloproliferative Neoplasms.

Background: Inflammation might play a critical role in the pathogenesis and progression of Philadelphia-negative myeloproliferative neoplasms (Ph−MPNs) with elevated inflammatory cytokines in peripheral blood (PB). However, the inflammatory status inside the bone marrow (BM), which is the place of malignancy origin and important microenvironment of neoplasm evolution, has not yet been elucidated.Methods: Inflammatory cytokine profiles in PB and BM of 24 Ph-MPNs patients were measured by a multiplex quantitative inflammation array. Cytokines that correlated between PB and BM were selected and then validated by ELISA in a separate cohort of 52 MPN patients. Furthermore, a panel of cytokines was identified and examined for potential application as non-invasive markers for the diagnosis and prediction of fibrosis progress of MPN subtypes.Results: The levels of G-CSF, I-309, IL-1β, IL-1ra, IL-12p40, IL-15, IL-16, M-CSF, MIG, PDGF-BB, and TIMP-1 in BM supernatants were significantly higher than those in PB (all p < 0.05). Linear correlations between BM and PB levels were found in 13 cytokines, including BLC, Eotaxin-2, I-309, sICAM-1, IL-15, M-CSF, MIP-1α, MIP-1δ, RANTES, TIMP-1, TIMP-2, sTNFRI, and sTNFRII (all R > 0.4 and p < 0.05). Levels of BLC, Eotaxin-2, M-CSF, and TIMP-1 in PB were significantly different from those in health controls (all p < 0.05). In PB, levels of TIMP-1 and Eotaxin-2 in essential thrombocythemia (ET) group were significantly lower than those in groups of prefibrotic primary myelofibrosis (pre-PMF) [TIMP-1: 685.2 (322.2–1,229) ng/ml vs. 1,369 (1,175–1,497) ng/ml, p = 0.0221; Eotaxin-2: 531.4 (317.9–756.6) pg/ml vs. 942.4 (699.3–1,474) pg/ml, p = 0.0393] and primary myelofibrosis (PMF) [TIMP-1: 685.2 (322.2–1229) ng/ml vs. 1,365 (1,115–1,681) ng/ml, p = 0.0043; Eotaxin-2: 531.4 (317.9–756.6) pg/ml vs. 1,010 (818–1,556) pg/ml, p = 0.0030]. The level of TIMP-1 in myelofibrosis (MF) >1 group was significantly higher than that in MF ≤ 1 group.Conclusion: Abnormal inflammatory status is present in MPN, especially in its BM microenvironment. Consistency between PB and BM levels was found in multiple inflammatory cytokines. Circulating cytokine levels of BLC, M-CSF, Eotaxin-2, and TIMP-1 reflected inflammation inside BM niche, suggesting potential diagnostic value for MPN subtypes and prognostic value for fibrosis progression.

Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy.

Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week’s GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.

P124 Are chronic pain syndromes associated with a unique cytokine profile? A systematic review and meta-analysis

Abstract Background/Aims The aetiology of primary chronic pain syndromes (CPS) is highly disputed. One theory suggests that pain is due to a pro-inflammatory cytokine milieu leading to nociceptive activation. We performed a systematic review and meta-analysis aiming to assess differences in cytokines levels in CPS patients versus healthy controls (HC). Methods Human studies published in English from PubMed, MEDLINE/Scopus and Cochrane databases were searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with cytokine measurements in CPS patients and HC. We excluded studies with underlying organic pathology. Quality assessment was completed using a modified version of the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. Study registered with PROSPERO (CRD42020193774). Results Initial search yielded 324 papers, 36 studies (3229 participants) eligible for systematic review and 26 studies (2048 participants) suitable for metaanalysis. There were reproducible findings supporting trends of cytokine levels comparing CPS patients with HC. Eotaxin (chemokine) however was consistently raised in CPS. Meta-analysis showed significantly increased tumour necrosis factor (TNF) (SMD=0.39, p = 0.0009, %95I=0.16-0.63, p &amp;lt; 0.001; I2=70%, Q2 p &amp;lt; 0.001), interleukin (IL)-6 (SMD=0.15, 8 (SMD=0.26, p = 0.01, 95%CI =0.05-0.47; I2=61%, Q2 p = 0.005) and IL-10 (SMD=0.61; %95 = 0.34-0.89, p &amp;lt; 0.001; I2 = 10%, Q2 p = 0.34) in CPS compared to HC. Conclusion We found significant differences in peripheral blood cytokine profiles of CPS patients compared to HC. However, the distinctive profile associated with CPS includes both pro-inflammatory (TNF-α, IL-6, IL-8), and anti-inflammatory cytokines (IL-10) in pooled analysis, as well as chemokine (eotaxin) signatures. Disclosure L. Furtado O'Mahony: None. A. Srivastava: None. P. Mehta: None. C. Ciurtin: None.

Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis.

ObjectivesThe aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokine levels in patients with diffuse CPS (fibromyalgia) vs healthy controls (HC).MethodsHuman studies published in English from the PubMed, MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO (CRD42020193774).ResultsOur initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared with HC, while the chemokine eotaxin, was consistently raised in fibromyalgia. Meta-analysis showed significantly increased TNF-α [standardized mean difference (SMD) = 0.36, 95% CI: 0.12, 0.60, P = 0.0034; I2 = 71%, Q2P = 0.0002], IL-6 (SMD = 0.15, 95% CI: 0.003, 0.29, P = 0.045; I2 = 39%, Q2P = 0.059), IL-8 (SMD = 0.26, 95% CI: 0.05, 0.47, P = 0.01; I2 = 61%, Q2P = 0.005) and IL-10 (SMD = 0.61, 95% CI: 0.34, 0.89, P < 0.001; I2 = 10%, Q2P = 0.34) in fibromyalgia patients compared with HC.ConclusionWe found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared with HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia.

Modulation of cytokine patterns and microbiome during pregnancy in IBD

ObjectivePregnancy may affect the disease course of IBD. Both pregnancy and IBD are associated with altered immunology and intestinal microbiology. However, to what extent immunological and microbial profiles are affected...

Abstract B063: Role of HIPEC and its association with regulatory T cells in ovarian cancer: Preliminary experience from tertiary care center in India

Abstract Introduction: Epithelial Ovarian cancer (EOC) is the most lethal Gynaecological Cancer and incidence is rapidly increasing in India and it is a leading cause of death due to its high relapse rate. Despite of multimodality treatment, the 5 years survival is dismal and for last three decades it is 15-30% and recurrence rate &amp;gt;70%. The Hyperthermic intraperitoneal chemotherapy (HIPEC) is a highly concentrated, heated chemotherapy, delivered directly to the abdominal cavity at the end of complete Cytoreduction surgery aiming to destroy the microscopic cancer cells. Experimental Procedure: Regulatory T cells (Tregs) play a crucial role in ovarian cancer suppression and its recurrence. However changes in Tregs population in patients with ovarian cancer after HIPEC in not yet known. On occurrence of cancer, immunological imbalance between Tregs and Th17 cells leads to cancer suppression or inflammation. Our study aims to understand the expression pattern of Tregs (CD4+,CD25+, CD127- ,IL10+,Foxp3+) and Th17(CD4+, CCR6+, IL17+, RORγ) and intracellular cytokine profile in peripheral blood by flow cytometry before and after the HIPEC in 1st week and 4th week. Summary: We have observed that percentage of Tregs in Ovarian Cancer patients (n=24) were high as compared to healthy controls before HIPEC and were reduced remarkably after 4 weeks of operation. Th17 cells frequency was low before HIPEC but in patients with good recovery Th17 cells are relatively high after 4 weeks of HIPEC. The percentage of Tregs was very high in stage III/IV before HIPEC treatment whereas there is some change in Th17 cells observed before and after HIPEC. This is a preliminary data results will be further confirmed by having more number of patients and after statistical analysis. Further we are also looking forFOXP3expressionat tissue and gene level by Immunohistochemistry (IHC) and real time PCR to compare the difference in expression of FOXP3 Conclusion: Our work raises the possibility that the HIPEC procedure not only kills tumour cells but also induces an efficient anticancer immune response, therefore opening new therapeutic windows for the patients of EOC. Citation Format: Mukurdipi Ray, Arshi Rizwan. Role of HIPEC and its association with regulatory T cells in ovarian cancer: Preliminary experience from tertiary care center in India [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B063. doi:10.1158/1535-7163.TARG-19-B063

Enhanced activation of circulating plasmacytoid dendritic cells in patients with Chronic Obstructive Pulmonary Disease and experimental smoking-induced emphysema

Plasmacytoid dendritic cells (pDCs) are key cells bridging the innate with adaptive immunity. However, the phenotypic characteristics of circulating pDCs and its role in smoking related-Chronic Obstructive Pulmonary Disease (COPD) remain largely unknown. The aim of this study was analyzed the phenotype of circulating pDCs and the expression of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells in patients with COPD by using multi-colour flow cytometry. The cytokine profiles in peripheral blood from all subjects were measured by ELISA. The influence of cigarette smoke on pDCs was evaluated in an experimental mouse model of emphysema. Circulating pDCs in patients with COPD and in mice exposed to cigarette smoke expressed high levels of co-stimulatory molecules CD40 or CD86 accompanied by exaggerated IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells. In vitro, cigarette smoke directly promoted pDCs maturation and release of IFN-α, IL-6 and IL-12, subsequently inducing differentiation of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells from mouse naïve CD8+T cells. These data suggested that circulating pDCs display an enhanced activation phenotype in patients with COPD and in experimental smoking mouse model of emphysema, which might contribute to exaggerated IFN-γ producing CD8+T and IL-17-producing CD8+T cell-mediated immune responses.

Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes

The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure

Limited information is available on the balance state of pro- and anti-inflammatory cytokines in patients with recurrent implantation failure (RIF). This study assessed the pro- and anti-inflammatory cytokines in plasma of 34 patients with RIF, compared with those of 25 women with a successful pregnancy in the first IVF/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI–ET) cycle. The IFN-γ, IL-1β, IL-6 and IL-4 concentrations were higher, whereas the TGF-β1 concentration was lower in the RIF group compared with the control group. Furthermore, the ratios of pro-inflammatory and anti-inflammatory cytokines IFN-γ/IL-4, IFN-γ/IL-10, IFN-γ/TGF-β1, IL-6/IL-10, IL-6/TGF-β1, IL-1β/TGF-β1 and TNF-α/TGF-β1 were higher in the RIF group (all P < 0.01). The results suggested a shift toward a pro-inflammatory state in peripheral blood of the patients with RIF.

AB0063 Gammadelta t cells and their intracellular cytokine profile in peripheral blood of patients with systemic lupus erythematosus

BackgroundGammadelta T cells represent a minor population of human peripheral blood T lymphocytes. As very rapid cytokine-producing cells, gammadelta T cells can regulate other lymphocytes activation and assist their local...

Serum cytokine profile in patients with hepatitis B e antigen-negative chronic active hepatitis B and inactive hepatitis B virus carriers

An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection. We have previously demonstrated no differences of T-lymphocyte subsets in blood between inactive hepatitis B s antigen (HBsAg) carriers and patients with HBeAg-negative chronic active hepatitis B. This study investigated the peripheral blood cytokine profile in patients with HBeAg-negative chronic active hepatitis B infection (Group A, n = 21) and inactive HBsAg carriers (Group B, n = 13). Serum cytokines [interferon (IFN)-γ, tumor necrosis factor-α, interleukin (IL)-1b, IL-4, IL-12, IL-10, IL-2, IL-5, IL-8] were analyzed by using flow cytometry. Patients with chronic active disease presented with significantly decreased levels of IFN-γ and IL-10 compared to inactive carriers (P = 0.048 and P = 0.008, respectively). In HBeAg-negative chronic active hepatitis B patients, a significant negative correlation of IFN-γ levels with serum hepatitis B viral load was noted (P = 0.021). In conclusion, patients with HBeAg-negative chronic active hepatitis B and HBsAg inactive carriers display a different cytokine profile. Decreased Th1 response observed in patients with chronic active hepatitis B could be implicated in the persistence of virus replication and ongoing progression of liver disease.