scholarly journals Serum Soluble Interleukin-2 Receptor Does Not Differentiate Complex Regional Pain Syndrome from Other Pain Conditions in a Tertiary Referral Setting

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
K. D. Bharwani ◽  
M. Dirckx ◽  
D. L. Stronks ◽  
W. A. Dik ◽  
F. J. P. M. Huygen ◽  
...  
Keyword(s):  
Disease Severity ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Pain Syndrome ◽  
Control Group ◽  
Healthy Controls ◽  
Tertiary Referral ◽  
Group A ◽  
Soluble Interleukin 2 Receptor

Previously, we showed that serum soluble interleukin-2 receptor (sIL-2R) levels, a marker for T-cell activation, were higher in complex regional pain syndrome (CRPS) patients than in healthy controls, suggesting pathogenic T-cell activation in CRPS. Additionally, sIL-2R levels discriminated well between CRPS and healthy controls with a high sensitivity (90%) and specificity (89.5%), suggesting a possible role for sIL-2R in the diagnosis of CRPS. In order to further validate this marker in the diagnostic workup of CRPS, we conducted this prospective cohort study in which we determined sIL-2R levels in patients that were referred to our tertiary referral center with a suspicion of CRPS in a limb, and subsequently compared sIL-2R levels between the patients that were diagnosed with CRPS (CRPS group) and those who were not (no CRPS group). A group of anonymous blood bank donors were used as a healthy control group. Furthermore, we explored the relationship between sIL-2R and CRPS disease severity using the CRPS severity score. Median sIL-2R levels of both the CRPS group (2809.0 pg/ml; Q3-Q1: 3913.0-1589.0) and no CRPS group (3654.0 pg/ml; Q3-Q1: 4429.0-2095.5) were significantly higher than that of the control group (1515.0 pg/ml; Q3-Q1: 1880.0-1150.0): CRPS vs. controls, p < .001 ; no CRPS vs. controls, p < 0.001 . Serum sIL-2R levels did not differ significantly between the CRPS and no CRPS group. A statistically significant negative correlation was observed between sIL-2R levels and the CRPS severity score ( r s = − 0.468 , p = 0.024 ). Our results confirm our previous findings of higher sIL-2R levels in CRPS patients than in healthy controls. We further showed that serum sIL-2R cannot differentiate between CRPS and other pain conditions of a limb in a tertiary referral setting. Interestingly, a negative correlation was found between sIL-2R and CRPS disease severity; this finding warrants further research into the relationship between sIL-2R and CRPS disease severity.

Platelets from Patients with Myocardial Infarction Can Activate T Cells in Vitro

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3448-3448 ◽  
Author(s):  
Elena E. Solomou ◽  
Vasilios Gizas ◽  
Theodora Babali ◽  
Angelos Perperis ◽  
Evgenia Verigou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
T Cell ◽  
Unstable Angina ◽  
T Cell Activation ◽  
Healthy Subjects ◽  
Cell Activation ◽  
Control Group ◽  
Healthy Controls

Abstract Specific aim: Our aim was to examine whether T cells can be activated by the circulating activated platelets from patients with myocardial infarction (with ST elevation-STEMI) Methods: After written informed consent was obtained, peripheral blood mononuclear cells (PBMCs) were isolated from heparinized venous blood obtained from 20 patients with STEMI (18 men and 2 women) at the time of hospital admission at diagnosis, before receiving any treatment, as well as 5 days and 30 days later. We also analyzed 10 healthy subjects (8 men and 2 women), and 5 patients with unstable angina who served as the disease control group. PBMCs were analyzed by flow cytometry with the following markers and their isotypic controls: CD4, CD25, CD69, and FOXP3. We also isolated platelet rich plasma or plasma alone from the patients and the healthy subjects, and used in mixed cultures with PBMCs. Results: We first examined T cell activation by measuring CD69 expression on CD4 T cells following incubation with platelets obtained from patients with STEMI. T cells treated with platelets from patients with STEMI showed increased expression of CD69 (as an activation marker) compared with T cells treated with platelets from healthy subjects (p<0.05, Figure 1). There was no T cell activation following incubation with plasma alone from patients or healthy controls. We then examined the percentages of CD4+CD25+hi (regulatory T cells). There was no statistical difference in Tregs between patients at presentation and controls (healthy subjects and disease control group). Five days later, patients with STEMI displayed increased levels of Tregs compared with the 2 control groups; one month later, Treg numbers returned to the initial presentation levels (p<0.05, Figure 2) Conclusion: To our knowledge we describe for the first time that platelets from patients with STEMI can activate T cells in vitro. In patients with STEMI, an increase in Tregs possibly in an effort to suppress immune system activation secondary to platelet activation, appears shortly after the infarct and normalizes a month later. Figure 1. T cell activation after treatment with platelets from patients with STEMI compared with the platelets from healthy controls or plasma alone Figure 1. T cell activation after treatment with platelets from patients with STEMI compared with the platelets from healthy controls or plasma alone Figure 2. Increased T regs in patients with STEMI , 5 days after admission (STEMI EXIT) ( UA;unstable angina, STEMI 1mfup; STEMI after one month) Figure 2. Increased T regs in patients with STEMI , 5 days after admission (STEMI EXIT) ( UA;unstable angina, STEMI 1mfup; STEMI after one month) Disclosures No relevant conflicts of interest to declare.

scholarly journals Elevated Plasma Levels of sIL-2R in Complex Regional Pain Syndrome: A Pathogenic Role for T-Lymphocytes?

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Krishna D. Bharwani ◽  
Maaike Dirckx ◽  
Dirk L. Stronks ◽  
Willem A. Dik ◽  
Marco W. J. Schreurs ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
Complex Regional Pain Syndrome ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Pain Syndrome ◽  
High Sensitivity ◽  
Healthy Controls ◽  
Good Discriminator ◽  
Soluble Interleukin 2 Receptor

The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 − Q1 = 5731 pg/ml − 3546 pg/ml) versus 1907 pg/ml (Q3 − Q1: 2206 pg/ml − 1374 pg/ml), p<0.001, resp.). Furthermore, sIL-2R level seems to be a good discriminator between CRPS patients and healthy controls with a high sensitivity (90%) and specificity (89.5%). Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS.

scholarly journals The Role of Soluble Interleukin-2 Receptor (sIL-2r) in Diagnosis of Adult Hemophagocytic Lymphohistiocytosis (HLH): A Single Center Retrospective Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 999-999
Author(s):  
Anna Hayden ◽  
Molly Lin ◽  
Sujin Park ◽  
Andre Mattman ◽  
Morris Pudek ◽  
...  
Keyword(s):  
Retrospective Study ◽  
T Cell ◽  
Disease Activity ◽  
T Cell Activation ◽  
Immune Activation ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Interleukin 2 Receptor ◽  
Soluble Interleukin 2 Receptor

Abstract Purpose: Serum soluble interleukin-2 receptor (sIL-2r) is considered an important disease marker in hemophagocytic lymphohistiocytosis (HLH). High levels of sIL2r are indicative of T-cell activation, and sIL2r &gt; 2400 U/mL was 93% sensitive and 100% specific for pediatric HLH in the HLH-2004 diagnostic criteria. [1] There are no published data on its performance characteristics in adults and very limited data in children. [2] We conducted a retrospective study to examine the diagnostic sensitivity and specificity of sIL-2r in diagnosing HPS/HLH, to assess how it varies with disease severity, determine its prognostic significance and ability to discriminate between subgroups of HPS/HLH. Methods: Retrospective data was collected on adult patients with at least one sIL-2r level at Vancouver General Hospital in Vancouver, Canada between March 2012 and April 2017. Patients were subdivided into HLH and non-HLH groups. Sensitivity, specificity, prognosis associated with sIL-2r &gt;10,000U/ml, utility as a marker of disease activity and mean sIL-2r between subgroups of HLH were evaluated. Non-HLH patients did not have convincing evidence to suggest HLH and did not receive HLH-specific therapy. Serum sIL-2r levels were enzyme-linked immunosorbent assay (ELISA; Siemens IMMULITE Immunoassay platform, adult reference range 241-846 U/ml). Results: 81 patients were included, 41 with HLH and 40 with an alternate diagnosis (non-HLH). Non-HLH diagnoses included sepsis, histiocyte disorders, multiple transfusions, liver disease, cardiac disease, autoimmune disease/vasculitis, and other inflammatory diseases. The sensitivity of sIL-2r &gt;2400 U/ml was 93% (95% CI 0.79 - 0.98) and specificity 63% (95% CI 0.46 - 0.77). Specificity improved to 93% (95% CI 0.79 - 0.98) with a threshold of sIL-2r &gt;10,000U/ml. Based on ROC curves, sIL2r is a good diagnostic test (AUC of 0.86) with a threshold that optimizes sensitivity and specificity of 2785U/ml and ferritin is a fair test (AUC 0.78) with an optimal threshold of 5775 ug/L. Similar to ferritin, sIL-2r levels correlated with disease activity in seven HLH patients that had multiple sIL-2r levels drawn during their disease course. Within the HLH group, sIL-2r &gt;10,000U/ml was not associated with worse prognosis. Higher sIL-2r levels were seen in malignancy associated HLH (MAHS) as compared to infection associated HLH (IAHS) and macrophage activation syndrome (MAS). Conclusion: sIL-2r &gt;2,400U/ml is a sensitive test for diagnosis of adult HPS/HLH and has utility in monitoring disease activity. At higher levels (sIL-2r &gt;10,000U/ml), this biomarker loses sensitivity but gains specificity in diagnosing HPS/HLH. Higher sIL-2r levels may indicate MAHS when the underlying etiology is unclear. In adults, secondary HPS/HLH is much more common than primary HLH, and all patients in this study were presumed to be secondary. The defining features of secondary HPS/HLH are pathologic immune activation and hypercytokinemia leading to end organ damage. SIL-2r is elevated in numerous conditions associated with T-cell activation and inflammation, such as lymphoma and autoimmune lymphoproliferative syndrome (ALPS), and larger prospective studies of adults with these and other conditions are needed to better define the specificity of increased sIL-2r for HPS/HLH. Since adult secondary HPS/HLH is increasingly diagnosed and treated in many centers, diagnostic criteria for adult secondary HPS/HLH should incorporate markers of hypercytokinemia and immune activation. References: 1. Janka, G.E. and E.M. Schneider, Modern management of children with haemophagocytic lymphohistiocytosis. Br J Haematol, 2004. 124(1): p. 4-14. 2. Lin, M., et al., Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review. Ann Hematol, 2017. 96(8): p. 1241-1251. Disclosures No relevant conflicts of interest to declare.

scholarly journals T cell-Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis (HLH) occurs in Non-Asians and is associated with a T cell activation state that is comparable to primary HLH

2021 ◽  
Author(s):  
Oded Shamriz ◽  
Deepak Kumar ◽  
Jenny Shim ◽  
Michael Briones ◽  
Maa-Ohui Quarmyne ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Severity ◽  
T Cell Activation ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Epstein Barr Virus ◽  
Cell Activation ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Barr Virus ◽  
Epstein Barr

Abstract PurposeT cell-Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (T cell-EBV-HLH) is prevalent in East Asia and has poor prognosis. Understanding of this disease is limited and literature regarding prevalence in North America is scarce. Herein, we summarize our experience. MethodsA retrospective analysis of T cell-EBV-HLH patients admitted to Children's Healthcare of Atlanta (GA, USA) from 2010-2020 was conducted. Additional immune studies were completed in a subset of patients. ResultsWe report 15 patients (10 months-19 years of age) diagnosed with T cell-EBV-HLH. Nine patients were Hispanic and the majority without primary HLH (p-HLH) gene defects. Soluble interleukin-2 receptor levels in T cell-EBV-HLH were significantly higher than other forms of secondary-HLH but comparable to p-HLH, and it correlated with disease severity at presentation. Natural-Killer cell function was decreased in most patients despite a negative workup for p-HLH. Depending on disease severity, initial therapy included dexamethasone or dexamethasone and etoposide. Refractory patients were managed with blended regimens that included one or more of these therapies - combination chemotherapy, alemtuzumab, emapalumab and nivolumab. Rituximab did not appreciably decrease EBV viremia in most patients. Alemtuzumab resulted in inflammation flare in 2 of the 3 patients. Two patients underwent allogeneic hematopoietic cell transplantation, with disease relapse noted in one. At a median follow-up of 3 years, 10 of the 15 patients are alive.ConclusionT cell-EBV-HLH occurs in the US among the non-Asian population, especially in those who are Hispanic. The amplitude of T cell activation noted in T cell-EBV-HLH is comparable to p-HLH.

scholarly journals Cellular and humoral immune responses associated with protection in sheep vaccinated against Teladorsagia circumcincta

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Cynthia Machín ◽  
Yolanda Corripio-Miyar ◽  
Julia N. Hernández ◽  
Tara Pérez-Hernández ◽  
Adam D. Hayward ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Anthelmintic Resistance ◽  
Gastrointestinal Nematodes ◽  
Control Group ◽  
Sheep Breeds ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Teladorsagia Circumcincta

AbstractDue to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.

scholarly journals CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help.

1993 ◽  
Vol 177 (6) ◽  
pp. 1791-1796 ◽  
Author(s):  
F A Harding ◽  
J P Allison
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Histocompatibility Complex ◽  
Necessary And Sufficient ◽  
Additional Antigen

The activation requirements for the generation of CD8+ cytotoxic T cells (CTL) are poorly understood. Here we demonstrate that in the absence of exogenous help, a CD28-B7 interaction is necessary and sufficient for generation of class I major histocompatibility complex-specific CTL. Costimulation is required only during the inductive phase of the response, and not during the effector phase. Transfection of the CD28 counter receptor, B7, into nonstimulatory P815 cells confers the ability to elicit P815-specific CTL, and this response can be inhibited by anti-CD28 Fab or by the chimeric B7-binding protein CTLA4Ig. Anti-CD28 monoclonal antibody (mAb) can provide a costimulatory signal to CD8+ T cells when the costimulatory capacity of splenic stimulators is destroyed by chemical fixation. CD28-mediated signaling provokes the release of interleukin 2 (IL-2) from the CD8+ CTL precursors, as anti-CD28 mAb could be substituted for by the addition of IL-2, and an anti-IL-2 mAb can block the generation of anti-CD28-induced CTL. CD4+ cells are not involved in the costimulatory response in the systems examined. We conclude that CD8+ T cell activation requires two signals: an antigen-specific signal mediated by the T cell receptor, and an additional antigen nonspecific signal provided via a CD28-B7 interaction.

Abstract 13287: Dendritic Cells Play a Critical Role in the Initiation of Atherosclerosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mengyao Jin ◽  
Peng Liu
Keyword(s):  
Cell Proliferation ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Critical Role ◽  
Cell Interaction ◽  
Plaque Formation ◽  
T Cell Proliferation ◽  
Control Group

Introduction: Dendritic cells (DCs) that are known as professional antigen-presenting cells have been found to pre-locate in non-inflammatory arterial wall and increasingly accumulate during atherosclerosis progression. Previous findings suggested that residential DCs in the intima are responsible for capturing modified lipids and forming foam cells during the initiation of atherosclerosis. Hypothesis: DC accumulation and enhanced DC-T cell interaction play a critical role in the initiation of atherosclerosis. Methods: We measured plaque formation, vascular DC accumulation and antigen-specific T cell proliferation mediated by isolated aortic cells in ApoE-/- mice, as well as DTR-CD11c/ApoE-/- or DTR-CD11b/ApoE-/- mice for conditional depletion of DCs or macrophages, respectively. A brief high-fat diet for 10 days was used as a model of initial atherosclerosis. Results: In addition to increased intimal DC accumulation and plaque formation in aortic roots, 10 days of HFD induced T cell infiltration in ApoE-/- mice, compared to those without HFD as the control. Isolated aortic cells from mice with 10-day HFD showed stronger capability in inducing antigen-specific T cell proliferation, compare to the control (HFD: 3.14±0.71%; no HFD: 1.56±0.36%; p=0.022). Single diphtheria toxin (DT) injection at day 1 yielded approximately 50% decrease in intimal DC accumulation, as well as 60% attenuation in plaque formation in DTR-CD11c/ApoE-/- mice after 10-day HFD. Capability of stimulating antigen-specific T cell proliferation was also impaired in aortic cells from DC-depleted mice (DT-treated: 1.62±0.30%; PBS-treated: 3.04±0.59%; p= 0.004), along with reduction in indirect conduction of T cell activation. In contrast, no significant changes were found in plaque formation and DC accumulation in DT-injected DTR-CD11b/ApoE-/- mice after 10 days of HFD, compared to control group. Furthermore, depletion of CD11b+ macrophages in either aortas or spleens didn’t alter capability of inducing antigen-specific T cell proliferation in DT-injected mice. Conclusions: These results suggested that vascular DCs rather than macrophages play a more important role in T cell activation and initiation of atherosclerosis.

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

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