Human Leukocyte antigen-DR Expression Research Articles

Monocyte programmed death ligand-1 expression is an early marker for predicting infectious complications in acute pancreatitis

BackgroundAcute pancreatitis (AP) is a life-threatening disease that requires early identification of patients at risk of developing infectious complications. Immunosuppression is an initial event that is key to AP pathogenesis. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system is reported to mediate evasion of host immune surveillance in many diseases; however, the relationship between PD-1/PD-L1 expression and these parameters or infectious complications in AP has not been elucidated. This study was conducted to determine whether PD-1 and PD-L1 are upregulated and to reveal the relationship between PD-1/PD-L1 expression and the development of infectious complications in AP.MethodsSixty-three patients with AP and 32 sex- and age-matched healthy control subjects were prospectively enrolled. On days 1 and 3 after the onset of AP, we measured PD-1 expression in peripheral CD4+ T cells and PD-L1 and human leukocyte antigen-DR (HLA-DR) expression in CD14+ monocytes using flow cytometry. Plasma interleukin (IL)-10 levels were measured by enzyme-linked immunosorbent assay.ResultsCompared with healthy volunteers, the percentages of PD-1-expressing CD4+ lymphocytes and PD-L1-expressing CD14+ monocytes were increased in patients with AP on days 1 and 3 after onset, especially those with infectious complications. Moreover, increased PD-1/PD-L1 expression was associated with increased occurrence of infectious complications, decreased circulating lymphocytes, and increased plasma IL-10 concentration. Multivariate regression analysis indicated that the increased percentage of PD-L1-expressing CD14+ monocytes was an independent risk factor for infectious complications in AP. Area under the ROC curve analysis showed the combination of Acute Physiology and Chronic Health Evaluation II score and PD-L1 and HLA-DR expression in CD14+ monocytes had high accuracy in predicting infectious complications in patients with AP.ConclusionsThe PD-1/PD-L1 system plays an essential role in the early immunosuppression of AP. PD-L1 expression in CD14+ monocytes may be a new marker for predicting risk of infectious complications in patients with AP.

Safety and Efficacy of Cortisol Phosphate in Hyaluronic Acid Vehicle in the Treatment of Dry Eye in Sjogren Syndrome.

Evaluation of 0.3% cortisol phosphate eye drops in hyaluronic acid vehicle in the treatment of dry eye in Sjogren Syndrome. This prospective, single-center, masked (single blind), randomized controlled study included 40 female patients divided into 2 groups, group 1 treated with Idracemi, 0.3% cortisol phosphate eye drops twice a day, and group 2 treated with Cortivis, 0.3% cortisol phosphate in hyaluronic acid vehicle, with the same posology. Screening (day -7), randomization (day 0), follow-up (day 7), and termination (day 28) visits were conducted. Symptoms (VAS) questionnaire, tear film breakup time, corneo-conjunctival stain, intraocular pressure (IOP) measurement, and fundus examination were performed at each visit. Conjunctival impression cytology for human leukocyte antigen-DR (HLA-DR) expression at visit 1 and 4 was also performed. No changes in IOP or fundus examination were observed in either group at each time point. Group 1 showed at day 28 a statistically significant amelioration of symptoms and reduction of HLA-DR expression. Group 2 showed at day 7 statistically significant improvement of corneal and conjunctival stain versus baseline and versus group 1; the symptom score was statistically significantly better than baseline and versus group 1 after 28 days too. The HLA-DR expression and the epithelial cell area were statistically significantly reduced versus baseline and versus group 1 at the same time. Cortisol phosphate proved to be safe and effective in treating dry eye in Sjogren Syndrome patients in both formulations. However, the formula with hyaluronic acid vehicle proved to be more effective. Both formulations were very well tolerated.

The Effects of High-Concentration Oxygen on Inflammatory Markers in Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

This study assessed effect of administration of high-concentration supplemental perioperative oxygen on systemic inflammatory and immune response in patients undergoing elective laparoscopic cholecystectomy. One hundred seventy-seven patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n=88) or 80% (n=89). White blood cells, peripheral lymphocytes subpopulation, human leukocyte antigen-DR, neutrophil elastase, interleukin (IL)-1 and IL-6, and C-reactive protein were investigated. Significantly higher concentration of neutrophil elastase, IL-1, IL-6 and C-reactive protein was detected postoperatively in the 30% FiO2 group patients in comparison with the 80% FiO2 group (P<0.05). Statistically significant change in human leukocyte antigen-DR expression was recorded postoperatively at 24 hours, as a reduction of this antigen expressed on monocyte surface in patients from 30% FiO2 group. This study demonstrated that high-concentration (80%) supplemental perioperative oxygen can lead to a reduction in postoperative inflammatory response and avoid postoperative immunosuppression.

Interferon-\u03b1-inducible Dendritic Cells Matured with OK-432 Exhibit TRAIL and Fas Ligand Pathway-mediated Killer Activity

Active human dendritic cells (DCs), which efficiently induce immune responses through their functions as antigen-presenting cells, exhibit direct anti-tumour killing activity in response to some pathogens and cytokines. These antigen-presenting and tumour killing abilities may provide a breakthrough in cancer immunotherapy. However, the mechanisms underlying this killer DC activity have not been fully proven, despite the establishment of interferon-α (IFN-α)-generated killer DCs (IFN-DCs). Here mature IFN-DCs (mIFN-DCs), generated from IFN-DCs primed with OK-432 (streptococcal preparation), exhibited elevated expression of CD86 and human leukocyte antigen-DR (minimum criteria for DC vaccine clinical trials) as well as antigen-presenting abilities comparable with those of mature IL-4-DCs (mIL-4-DCs). Interestingly, the killing activity of mIFN-DCs, which correlated with the expression of CD56 (natural killer cell marker) and was activated via the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand pathway, was stronger than that of IFN-DCs and remarkably stronger than that of mIL-4-DCs. Therefore, mIFN-DCs exhibit great potential as an anti-cancer vaccine that would promote both acquired immunity and direct tumour killing.

Dynamic monitoring of monocyte HLA-DR expression for the diagnosis, prognosis, and prediction of sepsis.

Sepsis, an under-recognized health problem, is a major cause of death. More than 750,000 individuals develop sepsis annually, of whom 215,000 die of the disease. Clinical and experimental evidence indicates that patients with sepsis present with rapid impairment of immune function; biomarkers are therefore needed to enable early detection of this condition. Reduced monocyte human leukocyte antigen-DR (HLA-DR) expression, which is measured by flow cytometry, is currently the most popular biomarker for sepsis detection. In addition, the determination of HLA-DR expression provides valuable information in terms of predicting mortality and risk of secondary infections. HLA-DR levels have been shown to be inversely correlated with the severity of sepsis and immune dysfunction. In this review, we provide an overview of the association between sepsis and HLA-DR expression in terms of the predictive value of the latter in sepsis.

Comparison of monocyte human leukocyte antigen-DR expression and stimulated tumor necrosis factor alpha production as outcome predictors in severe sepsis: a prospective observational study.

BackgroundIdentifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies. Little data exists comparing the ability of the two most well-studied markers of sepsis-induced immunosuppression, human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-ɑ) production, to predict mortality and morbidity. The purpose of this study was to compare HLA-DR expression and LPS-induced TNF-ɑ production as predictors of 28-day mortality and acquisition of secondary infections in adult septic patients.MethodsA single-center, prospective observational study of 83 adult septic patients admitted to a medical or surgical intensive care unit. Blood samples were collected at three time points during the septic course (days 1–2, days 3–4, and days 6–8 after sepsis diagnosis) and assayed for HLA-DR expression and LPS-induced TNF-ɑ production. A repeated measures mixed model analysis was used to compare values of these immunological markers among survivors and non-survivors and among those who did and did not develop a secondary infection.ResultsTwenty-five patients (30.1 %) died within 28 days of sepsis diagnosis. HLA-DR expression was significantly lower in non-survivors as compared to survivors on days 3–4 (p = 0.04) and days 6–8 (p = 0.002). The change in HLA-DR from days 1–2 to days 6–8 was also lower in non-survivors (p = 0.04). Median HLA-DR expression decreased from days 1–2 to days 3–4 in patients who developed secondary infections while it increased in those without secondary infections (p = 0.054). TNF-ɑ production did not differ between survivors and non-survivors or between patients who did and did not develop a secondary infection.ConclusionsMonocyte HLA-DR expression may be a more accurate predictor of mortality and acquisition of secondary infections than LPS-stimulated TNF-ɑ production in adult medical and surgical critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1505-0) contains supplementary material, which is available to authorized users.

Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma.

Human leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial. The pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas. In squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P < 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months; P = 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months; P = 0.002). Upregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.

Intravenous immunoglobulin treatment responsiveness depends on the degree of CD8 + T cell activation in Kawasaki disease

Kawasaki disease (KD) has become the most common cause of acquired heart disease in children and is also a risk factor for ischemic heart disease in adults. However, Kawasaki disease lacks specific laboratory diagnostic indices. Thus, this study analyzed the T cell activation profiles of Kawasaki disease and assessed their value in the diagnosis of Kawasaki disease and the prediction of intravenous immunoglobulin (IVIG) sensitivity. We analyzed human leukocyte antigen-DR (HLA-DR), CD69 and CD25 expression on peripheral blood CD4+ and CD8+ T cells during the acute phase of KD. We compared the percentages of HLA-DR+/CD69+/CD25+ T cells in the CD4+ and CD8+ T cell populations of IVIG-effective and IVIG-resistant groups. Receiver operating characteristic curves were used to assess the diagnostic value of the above parameters. The median percentage of CD8+HLA-DR+ T cells and the median ratio of CD8+HLA-DR+ T cells/CD8+CD25+ T cells were significantly elevated in the patient group compared with those in the control group during the acute phase of KD. Regarding the diagnosis of Kawasaki disease, the area under the ROC curve was 0.939 for the percentage of CD8+HLA-DR+ T cells. There was a significant difference in the ratio of CD8+HLA-DR+ T cells/CD8+CD69+ T cells between IVIG-resistant patients and IVIG-sensitive patients. Regarding IVIG sensitivity, the area under the ROC curve was 0.795 for it. Excessive CD8+ T cell activation, as well as an imbalance between CD8+ T cell activation and inhibition, underlies the pathogenesis of Kawasaki disease. The percentage of CD8+ HLA-DR+ T cells may be used as an index to diagnose Kawasaki disease. IVIG inhibits CD8+ T cell activation, but excessive CD8+ T cell activation may cause IVIG resistance. The ratio of CD8+HLA-DR+ T cells/CD8+CD69+ T cells may be used as a predictor of IVIG sensitivity.

C-C Chemokine Receptor Type 2 Expression on Monocytes Before Sepsis Onset Is Higher Than That of Postsepsis in Septic Burned Patients: A New Predictor for Sepsis in Burned Injury.

The present study aims to investigate the alterations in monocytes (Mo) and dendritic cells (DCs) in septic burned patients with a special focus on C-C chemokine receptor type 2 (CCR2) expressions on classical Mo. The phenotypes of Mo and DCs, particularly CCR2 expression on Mo, are not fully explored in severely burned patients with sepsis. The prospective cohort study was conducted in Ross Tilley Burn Centre and Sunnybrook Research Institute (Toronto, Canada). We enrolled 8 healthy patients and 89 burned patients with various burned sizes, of those burned patients, 12 were with sepsis. Blood was collected upon admission to the hospital and throughout their course in hospital. The expression of human leukocyte antigen-DR was determined on all DCs and Mo, along with CCR2 on CD14/CD16 Mo. We found a profound decrease in human leukocyte antigen-DR on Mo and DCs in burned patients with sepsis compared with healthy controls and nonseptic burned patients. In addition, septic burned patients presented an increased CCR2 expression on classical Mo (CD14/CD16), which was paralleled by greater chemokine (C-C motif) ligand 2 concentrations in the plasma when compared with controls and nonseptic burned patients. Furthermore, burned patients with sepsis had a more profound expansion of CD14/CD16 Mo when compared with nonseptic burned patients. Our results demonstrate that burned patients with sepsis have more profound impairment of monocytes and dendritic cells than burned patients without sepsis. With CCR2 level on Mo before sepsis onset being higher than postsepsis, CCR2 expression could be a new predictor of sepsis onset in severe burn injury.

Clinical-Grade Human Multipotent Adult Progenitor Cells Block CD8+ Cytotoxic T Lymphocytes.

Because multipotent adult progenitor cells (MAPCs) are among the noteworthy adult mesenchymal stem cell populations for immune therapy and have the advantage over mesenchymal stem cells (MSCs) of large-scale manufacturing and banking potential and thus prompt availability, it is important to understand how MAPCs interact with immune cells to validate their widespread therapeutic applicability. Cytotoxic immune effector cells play a crucial role in immune homeostasis and in the pathogenesis of some autoimmune diseases. This study assessed for the first time the in vitro influence of a clinical-grade human MAPC product (MultiStem) on the cytotoxic function of CD8+ T cells (CTLs) by evaluating the immunogenicity of MAPCs and the susceptibility of MAPCs toward CTL-mediated lysis and by analyzing the mechanism of MAPC-mediated modulation of CTL functionality. These results may represent a highly relevant contribution to the current knowledge and, in combination with the results of future phase II/III trials using MultiStem, could lead to an intriguing continuation of stem cell-based research for immunotherapy.

Effects of ulinastatin on immune function of patients with severe burn injury

To primarily evaluate the effects of ulinastatin on immune function of patients with severe burn injury. Forty patients with severe burn admitted to our ward from March 2013 to October 2015, conforming to the study criteria, were divided into conventional treatment group (CT, n=20) and ulinastatin treatment group (UT, n=20) according to the random number table and patient's consent. After admission, patients in group CT received antishock treatment, antibiotic treatment, debridement, skin grafting, and nutrition support, etc. On the basis of the above-mentioned treatment, patients in group UT received intravenous drip of ulinastatin from first day after admission twice a day, with a dosage of 8×10(5) U every time, for 7 days in addition. Peripheral venous blood samples were collected from patients in groups CT and UT on post treatment day (PTD) 1, 3, 5 and 7, respectively. Twenty healthy volunteer were selected as health control group (HC), and peripheral venous blood samples were collected on the first day of the study. Percentage of CD4(+) CD25(+) regulatory T lymphocytes (Tregs) was determined by flow cytometer. The proliferative activity of T lymphocytes was detected by microplate reader (denoted as absorbance value). Content of interleukin 2 (IL-2) in culture supernatant of T lymphocytes, and content of IL-4 and γ interferon (IFN-γ) in serum were detected by enzyme-linked immunosorbent assay. Expression of human leukocyte antigen-DR (HLA-DR) on CD14(+) monocytes was determined by flow cytometer. Data were processed with analysis of variance for repeated measurement, chi-square test, and LSD-t test. (1) Compared with that of volunteer in group HC, the percentage of CD4(+) CD25(+) Tregs of patients in group CT was significantly increased from PTD 1 to 7 (with t values from 13.303 to 26.043, P values below 0.01). Compared with that in group CT, the percentage of CD4(+) CD25(+) Tregs of patients in group UT was significantly decreased on PTD 5 and 7 (with t values respectively 8.317 and 15.071, P values below 0.01). (2) The proliferative activity of T lymphocytes of patients in group CT on PTD 1, 3, 5, and 7 was respectively 0.71±0.11, 0.61±0.15, 0.54±0.12, and 0.67±0.17, which was significantly lower than that in group HC (1.21±0.22, with t values from 8.686 to 11.957, P values below 0.01). The proliferative activity of T lymphocytes of patients in group UT on PTD 3, 5, and 7 were respectively 0.81±0.11, 0.85±0.14, and 1.08±0.13, which was significantly higher than that in group CT (with t values from 4.808 to 8.568, P values below 0.01). (3) Compared with those of volunteer in group HC, content of IL-2 in culture supernatant of T lymphocytes of patients in group CT was significantly decreased from PTD 1 to 7 (with t values from 8.073 to 9.288, P values below 0.01), content of IL-4 in serum of patients in group CT was significantly increased from PTD 1 to 7 (with t values from 18.926 to 41.451, P values below 0.01), and content of IFN-γ in serum of patients in group CT was significantly decreased from PTD 1 to 7 (with t values from 4.543 to 27.659, P values below 0.01). Compared with those in group CT, content of IL-2 in culture supernatant of T lymphocytes of patients in group UT was significantly increased from PTD 3 to 7 (with t values from 6.507 to 8.869, P values below 0.01), content of IL-4 in serum of patients in group UT was significantly decreased from PTD 3 to 7 (with t values from 6.922 to 8.843, P values below 0.01), and content of IFN-γ in serum of patients in group UT was significantly increased on PTD 5 and 7 (with t values respectively 5.369 and 13.521, P values below 0.01). (4) The percentages of CD14(+) monocytes with positive expression of HLA-DR of patients in group CT on PTD 1, 3, 5, and 7 were respectively (28±6)%, (25±7)%, (25±7)%, and (39±10)%, which were significantly lower than the percentage of volunteer in group HC [(87±8)%, with t values from 16.323 to 25.645, P values below 0.01]. The percentages of CD14(+) monocytes with positive expression of HLA-DR of patients in group UT on PTD 3, 5, and 7 were respectively (40±6)%, (42±9)%, and (49±10)%, which were significantly higher than those in group CT (with t values from 3.071 to 7.324, P values below 0.01). On the basis of CT, additional ulinastatin intervention can decrease CD4(+) CD25(+) Tregs percentage, improve the immune function of T lymphocytes and T helper cells, and increase expression of HLA-DR on CD14(+) monocytes of patients with severe burn injury, thus improve the immune function of patients.

Inflammation and innate immune function in critical illness.

The purpose of review is to highlight the inflammatory response in critical illness and the importance of immune monitoring and modulation in the diagnosis and treatment of critical illness-induced innate immune suppression. The pro and anti-inflammatory responses are known to be concurrently activated in many patients requiring intensive care, with innate immune suppression emerging as an important, and potentially reversible, complication of critical illness. The initial inflammatory response to critical illness is typically driven by innate immune cells, including neutrophils, monocytes, and macrophages. The proinflammatory mediators made by these cells are responsible for many of the pathophysiologic features of critical illness. Concurrent with this, however, is a compensatory anti-inflammatory response, including the elaboration of anti-inflammatory mediators and impairment of innate immune cell function. This includes reduction of monocyte human leukocyte antigen-DR expression and impairment of the ability of innate immune cells to produce tumor necrosis factor alpha when stimulated ex vivo. In its most severe form this is referred to as immunoparalysis, and is associated with markedly increased risks for secondary infection and death in the ICU. Prospective testing can detect this phenomenon, and immunostimulatory strategies, including the use of granulocyte macrophage-colony stimulating factor, have the potential to restore innate immune function in this setting.

A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease

To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). Phase 1/2 prospective, randomized, double-masked clinical trial. Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled. Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen. Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups (P= 0.06). However, burning sensation was more pronounced with tacrolimus (P= 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P= 0.01) and achieved significant improvement in TBUT when compared with baseline (P < 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27% reduction; P= 0.02), but was marginal with methylprednisolone (32% reduction; P= 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P= 0.003; methylprednisolone, P= 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group (P= 0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P= 0.04). Topical tacrolimus 0.05% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids.

Prolonged suppression of monocytic human leukocyte antigen–DR expression correlates with mortality in pediatric septic patients in a pediatric tertiary Intensive Care Unit

IntroductionImmunoparalysis is a syndrome with no clinical symptoms that occurs in some septic patients. Monocytic human leukocyte antigen–DR (mHLA-DR) expression has been used to identify patients in immunoparalysis and prolonged periods of reduced mHLA-DR expression have been correlated with a poor prognosis in sepsis. However, there is a lack of studies investigating mHLA-DR expression in pediatric septic patients. AimTo determine if mHLA-DR expression correlates with mortality in pediatric septic patients using the QuantiBRITE Anti HLA-DR/Anti-Monocyte,a Bechton Dickinson novel reagent that standardizes flow cytometry values. MethodsWe determined mHLA-DR expression in 30 patients with severe sepsis or septic shock admitted to the pediatric intensive care unit at Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, between January 2013 and February 2015. mHLA-DR expression was quantified between days 3 to 5 and 5 to 7 after the onset of sepsis and the ΔmHLA-DR (mHLA-DR2 − mHLA-DR1) was calculated. We also measured mHLA-DR levels in 21 healthy control patients. ResultsMean mHLA-DR expression was significantly lower in septic patients than in controls (P = .0001). Mortality was 46% in patients with negative ΔHLA-DR or <1000 mAb/cell and 7% in patients with positive ΔHLA-DR or >1000 mAb/cell. Mean ΔmHLA-DR levels were significantly different between survivors and non-survivors (P = .023). ConclusionΔHLA-DR correlates with mortality in pediatric patients with septic shock or severe sepsis. This is the first study to have used the QuantiBRITE Anti HLA-DR/Anti-Monocyte reagent to quantify monocyte HLA-DR expression in pediatric septic patients.

Severe Infection With Avian Influenza A Virus is Associated With Delayed Immune Recovery in Survivors.

Human infection with avian influenza A virus (H7N9) is a concern because of the mortality rate. Previously, we characterized immunological responses during active infection with it and reported evidence of impaired antigen-presenting capability, particularly in severely affected individuals. Here we describe an investigation of immunological responses during a 1-year follow-up of survivors of H7N9 infection. Survivors of H7N9 infection were classified as having had mild (n = 42) or severe infection (n = 26). Their immune status, including human leukocyte antigen-DR expression on monocytes, and their ability to mount cytokine responses were assessed at 1, 3, and 12 months postinfection.The total lymphocyte count and the percentages of different types of lymphocytes had normalized by 1 month postinfection. However, there was evidence of ongoing impairment of immune responses in those who had had severe infection. This included reduced human leukocyte antigen-DR expression on CD14 monocytes, reduced interferon-γ production by T cells, and higher plasma levels of the matrix metalloproteinases 2, 3, and 9. By 3 months postinfection, these had all normalized.After severe H7N9 infection, recovery of the antigen-presenting capability of monocytes and T-cell responses are delayed. This may lead to an increased vulnerability to secondary bacterial infections.

Effects of low and standard intra-abdominal pressure on systemic inflammation and immune response in laparoscopic adrenalectomy: A prospective randomised study.

BACKGROUND:The advantages of laparoscopic adrenalectomy (LA) over open adrenalectomy are undeniable. Nevertheless, carbon dioxide (CO2) pneumoperitoneum may have an unfavourable effect on the local immune response. The aim of this study was to compare changes in the systemic inflammation and immune response in the early post-operative (p.o.) period after LA performed with standard and low-pressure CO2 pneumoperitoneum.MATERIALS AND METHODS:We studied, in a prospective randomised study, 51 patients consecutively with documented adrenal lesion who had undergone a LA: 26 using standard-pressure (12-14 mmHg) and 25 using low-pressure (6-8 mmHg) pneumoperitoneum. White blood cells (WBC), peripheral lymphocyte subpopulation, human leucocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin (IL)-6 and IL-1, and C-reactive protein (CRP) were investigated.RESULTS:Significantly higher concentrations of neutrophil elastase, IL-6 and IL-1 and CRP were detected p.o. in the standard-pressure group of patients in comparison with the low-pressure group (P < 0.05). A statistically significant change in HLA-DR expression was recorded p.o. at 24 h, as a reduction of this antigen expressed on the monocyte surface in patients from the standard group; no changes were noted in low-pressure group patients (P < 0.05).CONCLUSIONS:This study demonstrated that reducing the pressure of the pneumoperitoneum to 6-8 mmHg during LA reduced p.o. inflammatory response and averted p.o. immunosuppression.

Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients.

Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients.

The Effect of Rosuvastatin on Markers of Immune Activation in Treatment-Naive Human Immunodeficiency Virus-Patients.

Background. Immune activation has been implicated in the excess mortality in human immunodeficiency virus (HIV)-infected patients, due to cardiovascular diseases and malignancies. Statins may modulate this immune activation. We assessed the capacity of rosuvastatin to mitigate immune activation in treatment-naive HIV-infected patients.Methods. In a randomized double-blind placebo-controlled crossover study, we explored the effects of 8 weeks of rosuvastatin 20 mg in treatment-naive male HIV-infected patients (n = 28) on immune activation markers: neopterin, soluble Toll-like receptor (TLR)2, sTLR4, interleukin (IL)-6, IL-1Ra, IL-18, d-dimer, highly sensitive C-reactive protein, and CD38 and/or human leukocyte antigen-DR expression on T cells. Baseline data were compared with healthy male controls (n = 10). Furthermore, the effects of rosuvastatin on HIV-1 RNA, CD4/CD8 T-cell count, and low-density lipoprotein cholesterol were examined and side effects were registered.Results. T-cell activation levels were higher in patients than in controls. Patients had higher levels of circulating IL-18, sTLR2, and neopterin (all P < .01). Twenty patients completed the study. Rosuvastatin increased the CD4/CD8 T-cell ratio (P = .02). No effect on other markers was found.Conclusions. Patients infected with HIV had higher levels of circulating neopterin, IL-18, sTLR2, and T-cell activation markers. Rosuvastatin had a small but significant positive effect on CD4/CD8 T-cell ratio, but no influence on other markers of T-cell activation and innate immunity was identified (The Netherlands National Trial Register [NTR] NTR 2349, http://www.trialregister.nl/trialreg/index.asp).

Solution-Phase Crosstalk and Regulatory Interactions Between Multipotent Adult Progenitor Cells and Peripheral Blood Mononuclear Cells.

Multipotent adult progenitor cells (MAPCs) are adult adherent stromal stem cells currently being assessed in clinical trials for acute graft versus host disease with demonstrated immunomodulatory capabilities and the potential to ameliorate detrimental autoimmune and inflammation-related processes. Anti-CD3/anti-CD28 (3/28) activation of T cells within the peripheral blood mononuclear cell (PBMC) compartment was performed in the presence or absence of MAPCs. Liquid chromatography-coupled tandem mass spectrometry was used to characterize the differential secretion of proteins, and transcriptional profiling was used to monitor mRNA expression changes in both cell populations. Overall, 239 secreted and/or ectodomain-shed proteins were detected in the secretomes of PBMCs and MAPCs. In addition, 3/28 activation of PBMCs induced differential expression of 2,925 genes, and 22% of these transcripts were differentially expressed on exposure to MAPCs in Transwell. MAPCs exposed to 3/28-activated PBMCs showed differential expression of 1,247 MAPC genes. Crosstalk was demonstrated by reciprocal transcriptional regulation. Secretome proteins and transcriptional signatures were used to predict molecular activities by which MAPCs could dampen local and systemic inflammatory responses. These data support the hypothesis that MAPCs block PBMC proliferation via cell cycle arrest coupled to metabolic stress in the form of tryptophan depletion, resulting in GCN2 kinase activation, downstream signaling, and inhibition of cyclin D1 translation. These data also provide a plausible explanation for the immune privilege reported with administration of donor MAPCs. Although most components of the major histocompatibility complex class II antigen presentation pathway were markedly transcriptionally upregulated, cell surface expression of human leukocyte antigen-DR is minimal on MAPCs exposed to 3/28-activated PBMCs. This study documents experiments quantifying solution-phase crosstalk between multipotent adult progenitor cells (MAPCs) and peripheral blood mononuclear cells. The secretome and transcriptional changes quantified suggest mechanisms by which MAPCs are hypothesized to provide both local and systemic immunoregulation of inflammation. The potential impact of these studies includes development of a robust experimental framework to be used for preclinical evaluation of the specific mechanisms by which beneficial effects are obtained after treatment of patients with MAPCs.

Effect of hemofiltration combined with hemoabsorption on improvement of immune function in septic patients with low expression of human leukocyte antigen DR

To investigate the effect on improving immune function by hemofiltration combined with hemoabsorption in septic patients with low human leukocyte antigen DR (HLA-DR) expression. A prospective randomized controlled trial was conducted. Sixty sepsis patients aged over 18 years, with HLA-DR expression lower than 30% were enrolled, and they were randomly divided into experimental group and control group, n = 30 in each group. The patients were treated with standard operating procedure for sepsis, and hemofiltration combined with hemoabsorption were added in addition in the experimental group within 1-3 days. The continuous venovenous hemofiltration (CVVH) mode was performed, with former dilution volume 4 L/h, and the hemofilter HF2000 was carried out with blood absorber HA-330H. The expression of HLA-DR in peripheral blood mononuclear cells was determined before the treatment and 3, 5, 7 days after treatment. Acute physiology and chronic health evaluation II (APACHE II) score, duration of mechanical ventilation, length of intensive care unit (ICU) stay, and 28-day survival rate were evaluated in both groups. The HLA-DR expression before treatment in experimental group and control group was both lower than 30%, and there was no statistical difference [(25.9 ± 7.3)% vs. (26.4 ± 6.7)%, P > 0.05]. The HLA-DR expression at 3, 5, 7 days after treatment in experimental group was gradually increased, and it was significantly higher than that of the control group [3 days: (38.9 ± 8.6)% vs. (29.3 ± 7.1)%, 5 days: (42.7 ± 9.2)% vs. (31.4 ± 6.5)%, 7 days: (40.9 ± 8.5)% vs. (29.4 ± 6.7)%, all P < 0.05]. There was no significant difference in APACHE II score before treatment between experimental group and control group (22.4 ± 5.3 vs. 21.7 ± 6.2, P > 0.05). APACHE II score at 3, 5, and 7 days after treatment was gradually decreased in experimental group, and it was obviously lower than that of the control group (3 days: 18.6 ± 3.6 vs. 20.5 ± 4.3, 5 days: 15.8 ± 3.9 vs. 21.1 ± 4.4, 7 days: 14.9 ± 4.2 vs. 19.8 ± 3.7, all P < 0.05). Compared with the control group, the duration of mechanical ventilation (days: 13.3 ± 3.4 vs. 19.8 ± 3.7, t = 6.432, P = 0.003) and length of ICU stay (days: 20.7 ± 3.9 vs. 26.8 ± 4.7, t = 5.452, P = 0.006) in experimental group were significantly shortened, and the 28-day survival rate was significantly elevated (83.3% vs. 73.3%, χ2 = 3.121, P = 0.016). Hemofiltration combined with hemoabsorption can improve the expression of HLA-DR in sepsis patients with low expression of HLA-DR, and it can improve immune function and prognosis of sepsis patients in certain degree.