HLA-DR genetic polymorphisms and hepatitis B virus mutations affect the risk of hepatocellular carcinoma in Han Chinese population.

BACKGROUND: Human leucocyte antigen (HLA)-DR plays a crucial role in the immune response against hepatitis B virus (HBV). We aimed to investigate the associations of HLA-DR single nucleotide polymorphisms (SNPs) with the generation of hepatocellular carcinoma (HCC)-related HBV mutations. The effects of HLA-DR SNPs and their interactions with HBV mutations on HCC risks were also determined. METHODS: Five HLA-DR SNPs (rs3135363, rs9268644, rs35445101, rs24755213, and rs984778) were genotyped in 792 healthy controls, 586 chronic hepatitis B (CHB) patients, 536 liver cirrhosis (LC) patients, and 1500 HCC patients using quantitative PCR. Sanger sequencing was used to identify the HBV mutations. Logistic regression model was performed to evaluate the association of HLA-DR SNPs with HCC risk and the frequencies of HCC-related HBV mutations. RESULTS: The variant genotypes at rs3135363, rs9268644, rs35445101, rs24755213, and rs984778 were associated with decreased HCC risks. In genotype C HBV-infected subjects, variant genotypes of these SNPs were associated with decreased frequencies of HCC-related HBV mutations such as C1653T, T1674C/G, G1719T, T1753A/C, A1762T/G1764A, A1846T, G1896A, G1899A, and preS deletion. AG genotype at rs3135363, CA genotype at rs9268644, and AG genotype at rs24755213 reduced the generation of T1753A/C and G1896A in genotype B HBV-infected subjects, respectively. In addition, the interactions of rs3135363, rs9268644, rs24755213 with C1653T, T1753A/C, A1846T, and G1896A decreased the risks of HCC. CONCLUSIONS: HLA-DR genetic polymorphisms might predispose the host to immunoselection of HCC-related HBV mutations and affect the HCC risks possibly through interacting with HBV mutations.

Single-cell transcriptome profiling of sepsis identifies HLA-DRlowS100Ahigh monocytes with immunosuppressive function.

BACKGROUND: Sustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking. METHODS: We adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9-/- mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage. RESULTS: ScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression. CONCLUSIONS: This study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.

Utility of monocyte HLA-DR and rationale for therapeutic GM-CSF in sepsis immunoparalysis.

Sepsis, a heterogeneous clinical syndrome, features a systemic inflammatory response to tissue injury or infection, followed by a state of reduced immune responsiveness. Measurable alterations occur in both the innate and adaptive immune systems. Immunoparalysis, an immunosuppressed state, associates with worsened outcomes, including multiple organ dysfunction syndrome, secondary infections, and increased mortality. Multiple immune markers to identify sepsis immunoparalysis have been proposed, and some might offer clinical utility. Sepsis immunoparalysis is characterized by reduced lymphocyte numbers and downregulation of class II human leukocyte antigens (HLA) on innate immune monocytes. Class II HLA proteins present peptide antigens for recognition by and activation of antigen-specific T lymphocytes. One monocyte class II protein, mHLA-DR, can be measured by flow cytometry. Downregulated mHLA-DR indicates reduced monocyte responsiveness, as measured by ex-vivo cytokine production in response to endotoxin stimulation. Our literature survey reveals low mHLA-DR expression on peripheral blood monocytes correlates with increased risks for infection and death. For mHLA-DR, 15,000 antibodies/cell appears clinically acceptable as the lower limit of immunocompetence. Values less than 15,000 antibodies/cell are correlated with sepsis severity; and values at or less than 8000 antibodies/cell are identified as severe immunoparalysis. Several experimental immunotherapies have been evaluated for reversal of sepsis immunoparalysis. In particular, sargramostim, a recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF), has demonstrated clinical benefit by reducing hospitalization duration and lowering secondary infection risk. Lowered infection risk correlates with increased mHLA-DR expression on peripheral blood monocytes in these patients. Although mHLA-DR has shown promising utility for identifying sepsis immunoparalysis, absence of a standardized, analytically validated method has thus far prevented widespread adoption. A clinically useful approach for patient inclusion and identification of clinically correlated output parameters could address the persistent high unmet medical need for effective targeted therapies in sepsis.

Breast Cancer Patients: Who Would Benefit from Neoadjuvant Chemotherapies?

Neoadjuvant chemotherapy (NACT) was developed with the aims of shrinking tumors or stopping cancer cells from spreading before surgery. Unfortunately, not all breast cancer patients will benefit from NACT, and thus, patients must weigh the risks and benefits of treatment prior to the initiation of therapy. Currently, the data for predicting the efficacy of NACT is limited. Molecular testing, such as Oncotype DX, MammaPrint, and Curebest 95GC, have been developed to assist which breast cancer patients will benefit from the treatment. Patients with an increased level of Human Leukocyte Antigen-DR isotype, tumor-infiltrating lymphocytes, Fizzy-related protein homolog, and a decreased level of tumor-associated macrophages appear to benefit most from NACT.

Topical gel of mesenchymal stem cells-conditioned medium under TNF-α precondition accelerates wound closure healing in full-thickness skin defect animal model.

Mesenchymal Stem Cells (MSCs) under TNF-α stimulation (MSC-CM-T) can release numerous trophic and survival molecules that have a promising prospect in wound healing acceleration. However, the effective levels of MSC-CM-T in topical gel preparation to accelerate wound healing should be further explored. The aim of this study was to investigate the effects of MSC-CM-T in topical gel preparation in accelerating optimal wound healing through analyzing PDGF levels, wound closure rate percentages, and fibroblast density appearances. Twenty-four male Wistar rats were performed a full-thickness excision. The group studies were randomly assigned into four subgroups: control gel, control medium, and two treatment groups: MSC-CM-T topical gel at doses of 100 µL and 200 µL (T1 and T2, respectively). Wound closure rates were measured by standard caliper, platelet-derived growth factor (PDGF) levels were analyzed using ELISA on days 3 and 6, whereas the fibroblast density appearances were determined using hematoxylin-eosin staining. This study found a significant increase in PDGF levels in all treatment groups on days 3 and 6. These findings were in line with the increase of wound closure rates in all treatment groups on day 6, in which the high dose of MSC-CM-T was more effective in initiating the increase of wound closure rate. We also found the fibroblast density appearances on day 6 in the T2 group. We conclude that the topical gel of MSC-CM-T is more effective in accelerating wound closure healing through increasing PDGF levels and wound closure percentages and fibroblast density appearances in the skin defect animal models.

Prognostic value of peripheral blood CD14+HLA-DR+ monocytes in patients with acute pancreatitis.

Acute pancreatitis (AP) is characterized by a potent pro-inflammatory response and concomitant anti-inflammatory response leading to a state of immunosuppression. Decreased HLA (Human Leukocyte Antigen)-DR expression on monocytes is a reliable cellular marker of immune suppression. The main objective of this study was to investigate the clinical value of the percentage of peripheral blood CD14+ HLA-DR+ monocytes (mHLA-DR) for diagnosis and assessment of severity, development of organ failures (OF), local complications (LC), and infected necrosis (IN), and outcome in patients with AP. Flow cytometry was used to measure the percentage of peripheral blood mHLA-DR at different time points in 82 patients with AP enrolled during the period of 2012-2018 admitted to University Hospital Stara Zagora, Bulgaria. The percentages of peripheral blood mHLA-DR in AP patients were significantly associated with severity, development of LC, OF, IN (measured at admission, on the 48th hour and on the 5th day) and with outcome (measured on the 5th day) of AP. The value of peripheral blood mHLA-DR may be used as a biological marker in the diagnosis and assessment of severity, development of OF, LC, IN and to predict outcome in AP.

Clinical Features of Fatal Pandemic Influenza A/H1N1 Infection Complicated by Invasive Pulmonary Fungal Infection.

BACKGROUND: Severe pneumonia caused by influenza virus infection can be secondary to invasive pulmonary fungal (IPF) infection. OBJECTIVES: This study aimed to summarize the incidence of IPF infection secondary to influenza virus infection and further explore its etiologic mechanism and high-risk factors. METHODS: All adult patients with confirmed influenza A (H1N1) virus infection admitted to the intensive care units (ICUs) of Nanjing Drum Hospital from November 2017 to March 2018 were retrospectively selected. The differences in baseline factors, risk factors, immune function and outcome parameters were studied between patients with and without IPF. RESULTS: Of the 19 critically ill patients with H1N1 infection, 11 (57.9%) developed IPF infection after 7 days of ICU admission. Two patients had proven and nine probable IPF infection. A difference in human leukocyte antigen-DR isotype (△HLA-DR; day 7-day 1) was found between the two groups. △HLA-DR (day 7-day 1) was higher in patients with no IPF infection than in those with IPF infection [(14.52 ± 14.21)% vs ( - 11.74 ± 20.22)%, P = 0.019]. The decline in HLA-DR indicated impaired immune function secondary to fungal infection in patients with H1N1 infection. CONCLUSIONS: IPF infection was diagnosed in 57.9% of critically ill patients with H1N1 virus infection after a median of 7 days following ICU admission. A continuous decline in immune function could lead to the development of IPF infections. Dynamic monitoring of immune function may help in the early detection of IPF infection.

Monocyte subsets study in children with Mycoplasma pneumoniae pneumonia.

The aim of this study was to evaluate the changes in the three subsets of monocyte (classical, intermediate, and non-classical) and the expression of human leukocyte antigen-DR (HLA-DR) on monocyte subsets during MP pneumonia in children. Monocyte subsets were analyzed in the peripheral blood of healthy volunteers and MP pneumonia patients at the stages of admission and remission after clinical therapy. They were defined as classical (CD14+CD16-), intermediate (CD14brightCD16+), and non-classical (CD14dimCD16+) using flow cytometry. Furthermore, three subsets of monocyte were analyzed for the expression of HLA-DR. Patients with MP pneumonia at admission had a higher proportion of intermediate and non-classical monocytes than healthy subjects (all P < 0.05). The proportion of intermediate subset and non-classical subset was lower in MP pneumonia patients at remission than at admission (all P < 0.05). In comparison with the other monocyte subsets, intermediate subset showed a significantly higher percentage of HLA-DR in MP pneumonia patients at admission (P < 0.05). Further analysis revealed that the expression of HLA-DR on intermediate subset was lower in severe patients than in non-severe patients (P < 0.05).Our data has shown for the first time that MP pneumonia is associated with the increased proportion of non-classical and intermediate monocytes, indicating the involvement of monocyte-related mechanisms in the pathogenesis of this disease. Additionally, the decreased expression of HLA-DR on CD14brightCD16+ subset may be a potential indicator of the severity of MP pneumonia.

Construction and Screening of an Antigen-Derived Peptide Library Displayed on Yeast Cell Surface for CD4+ T Cell Epitope Identification.

Antigenic peptides (termed T cell epitopes) are assembled with major histocompatibility complex (MHC) molecules and presented on the surface of antigen-presenting cells (APCs) for T cell recognition. T cells engage these peptide-MHCs using T cell receptors (TCRs). Because T cell epitopes determine the specificity of a T cell immune response, their prediction and identification are important steps in developing peptide-based vaccines and immunotherapies. In recent years, a number of computational methods have been developed to predict T cell epitopes by evaluating peptide-MHC binding; however, the success of these methods has been limited for MHC class II (MHCII) due to the structural complexity of MHCII antigen presentation. Moreover, while peptide-MHC binding is a prerequisite for a T cell epitope, it alone is not sufficient. Therefore, T cell epitope identification requires further functional verification of the MHC-binding peptide using professional APCs, which are difficult to isolate, expand, and maintain. To address these issues, we have developed a facile, accurate, and high-throughput method for T cell epitope mapping by screening antigen-derived peptide libraries in complex with MHC protein displayed on yeast cell surface. Here, we use hemagglutinin and influenza A virus X31/A/Aichi/68 as examples to describe the key steps in identification of CD4+ T cell epitopes from a single antigenic protein and the entire genome of a pathogen, respectively. Methods for single-chain peptide MHC vector design, yeast surface display, peptide library generation in Escherichia coli, and functional screening in Saccharomyces cerevisiae are discussed.

Study on association of human leukocyte antigen-DRB1 alleles amongst Bangladeshi patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic and autoimmune disease affecting 0.5-1% of the world population. Genetic and environmental factors are already established as being involved in the development of RA. Different human leukocyte antigen (HLA)-DRB1 alleles have major pathogenic effects to the development of RA. OBJECTIVE: To determine the HLA-DRB1 allelic frequency of RA in one Bangladeshi tertiary care center. METHODS: This case-control study was conducted at the Microbiology and Rheumatology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU). Fifty-two patients diagnosed as having RA and 52 healthy controls were enrolled. Buccal swabs were collected from all subjects and HLA-DRB1 typing was carried out with polymerase chain reaction with sequence-specific primers (PCR-SSP) of low resolution. Blood was also collected for auto-antibodies (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) detection from all subjects. RF was detected by nephelometry and anti-CCP was detected by using the enzyme-linked immunosorbent assay method. Statistical associations of HLA antigen between the groups were determined by chi-square test. RESULTS: In RA patients DR*04 and DR*10 were found at the DRB1 locus at higher frequencies (20.5%, P = 0.0035 and 18.3%, P = 0.0045, respectively). However, the frequency of DR*15 was significantly lower (P = 0.005) in RA cases (18.3%) than the control group (35.6%). The frequencies of autoantibodies (anti-CCP and RF) were compared between approximate shared epitope (SE) positive and SE negative patients, and no significant association was found. CONCLUSIONS: In this study DRB1*04 and DRB1*10 alleles were significantly associated with RA patients while DRB1*15 was found more in the control group.

Effect of Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma longa L. on Th1- and Th2-cytokine responses and human leukocyte antigen-DR expression in peripheral blood mononuclear cells of septic patients.

ETHNOPHARMACOLOGICAL RELEVANCE: Many traditional Chinese medicines (TCM), such as Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma longa L., have been reported to have various immune-modulatory effects. AIM OF THE STUDY: To determine the effects of extracts from these three TCM on type 1 T help (Th1)- and Th2-cytokine responses and human leukocyte antigen (HLA)-DR expression in peripheral blood mononuclear cells (PBMCs) obtained from septic patients. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-stimulated PBMCs of healthy controls and septic patients were cultured for 48 hs with or without 0.05/0.1 mg/ml of TCM extract. HLA-DR expression in monocytes was detected using flow cytofluorimetry. The interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin (IL)- 2, IL-5, IL-10, and IL-13 levels in supernatants were measured with a human enzyme-linked immunosorbent assay. RESULTS: Treatment with either 0.05 or 0.1 mg/ml of C. longa L. extract significantly restored the percentage of HLA-DR-positive monocytes, which was decreased by LPS in control and patient groups. Treatment with 0.05 or 0.1 mg/ml E. ulmoides Oliv. and C.longa L. extract decreased IL-10 production from LPS-stimulated PBMCs of controls and patients. In patients with sepsis, C. longa L. extract decreased IL-10 production to a greater degree than did E. ulmoides Oliv extract. Although IFN-γ, TNF-α, or IL-13 productions from LPS-stimulated PBMCs were influenced by E. ulmoides Oliv., G. pentaphyllum (Thunb.) Makino, or C. longa L. in control or sepsis groups in this study, only the influence of IL-10 was consistent in both control and sepsis groups. CONCLUSIONS: By enhancing monocyte HLA-DR expression and decreasing IL-10 production, C. longa L. might help restore inflammatory responses in septic patients to eradicate pathogens.

Analysis of clinical characteristics of bloodstream infection in patients with immune function inhibition / 中华危重病急救医学

Objective To analyze the clinical characteristics of bloodstream infection in patients with immune function inhibition. Methods A retrospective analysis was conducted. 234 patients with bloodstream infection admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 1st in 2015 to December 31st in 2017 were enrolled. According to the immune function on the day of bloodstream infection, they were divided into normal immune function group [human leukocyte antigen DR (HLA-DR) > 30%, n = 144] and immunosuppression group (HLA-DR ≤30%, n = 90). The gender, age, primary disease, complication, acute physiology and chronic health evaluationⅡ (APACHEⅡ) with 24 hours after ICU admission, sequential organ failure assessment (SOFA) score, etiology, infection parameters on the day of bloodstream infection [peak temperature, white blood count (WBC), neutrophils ratio, procalcitonin (PCT), and C-reactive protein (CRP)] and prognosis parameters (bacterial clearance time, the length of ICU and hospital stay, 28-day mortality) between the two groups were analyzed. Results 234 patients were enrolled in the final analysis, including 132 males and 102 females, with an average age of (60.5±18.4) years old. Severe pneumonia and abdominal infection were the main causes of primary diseases. There was no significant difference in gender composition, age, APACHEⅡ, SOFA score, other complications and primary morbidity between the two groups except that the proportion of malignant tumors in the immunosuppressive group was higher than that in the normal immune function group [43.3% (39/90) vs. 41.7% (60/144), P < 0.05]. Compared with the normal immune function group, the Gram-positive cocci infection rate in the immunosuppressive group was significantly lowered [40.0% (36/90) vs. 56.2% (81/144)], Gram-negative bacilli infection rate [50.0% (45/90) vs. 39.6% (57/144)] and fungus infection rate [10.0% (9/90) vs. 4.2% (6/144)] were significantly increased (both P < 0.05). The levels of WBC, neutrophils ratio, and PCT on the day of bloodstream infection in the immunosuppressive group were significantly lower than those of normal immune function group [WBC (×109/L): 10.2±2.1 vs. 13.5±3.6, neutrophils ratio: 0.87±0.17 vs. 0.96±0.22, PCT (μg/L): 1.3±1.1 vs. 4.7±2.1, all P < 0.05], but no significant difference in the peak temperature (℃: 38.5±1.7 vs. 38.9±1.3) or CRP (mg/L: 134.0±42.6 vs. 164.0±55.8) was found as compared with normal immune function group (both P > 0.05). Compared with the normal immune function group, the bacterial clearance time in the immunosuppressive group was significantly prolonged (days: 16.0±10.1 vs. 12.3±4.7), 28-day mortality was significantly increased [61.1% (55/90) vs. 44.4% (64/144)] with statistical significances (both P < 0.05), but no significance was found in the length of ICU stay (days: 21.0±17.1 vs. 18.7±10.4) or the length of hospital stay (days: 36.0±28.1 vs. 33.8±16.8, both P > 0.05). Conclusion Gram-negative bacilli was the main pathogen of bloodstream infection in immunosuppressive patients, and the fungal infection rate was high, inflammation reaction was not obvious, bacterial clearance time was long, and prognosis was poor.

Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires.

Human leukocyte antigen (HLA)-DR15 is a haplotype associated with multiple sclerosis. It contains the two DRB* genes DRB1*1501 (DR2b) and DRB5*0101 (DR2a). The reported anchor motif of the corresponding HLA-DR molecules was determined in 1994 based on a small number of peptide ligands and binding assays. DR2a could display a set of peptides complementary to that presented by DR2b or, alternatively, a similar peptide repertoire but recognized in a different manner by T cells. It is known that DR2a and DR2b share some peptide ligands, although the degree of similarity of their associated peptidomes remains unclear. In addition, the contribution of each molecule to the global peptide repertoire presented by the HLA-DR15 haplotype has not been evaluated. We used mass spectrometry to analyze the peptide pools bound to DR2a and DR2b, identifying 169 and 555 unique peptide ligands of DR2a and DR2b, respectively. The analysis of these sets of peptides allowed the refinement of the corresponding binding motifs revealing novel anchor residues that had been overlooked in previous analyses. Moreover, the number of shared ligands between both molecules was low, indicating that DR2a and DR2b present complementary peptide repertoires to T cells. Finally, our analysis suggests that, quantitatively, both molecules contribute to the peptide repertoire presented by cells expressing the HLA-DR15 haplotype.

Similarities and Differences in Autoimmune Hepatitis Epidemiology between East and West: Autoimmune Hepatitis in East Asia, Southeast Asia, and South Asia.

BACKGROUND: Autoimmune hepatitis (AIH) is a relatively rare disease that can develop regardless of age or ethnicity. However, its clinical features differ between eastern and western populations due to several heterogeneous genetic and environmental factors. We herein report the clinical characteristics of AIH patients in East Asia, Southeast Asia, and South Asia. SUMMARY AND KEY MESSAGES: The prevalence of AIH in eastern countries is considered to be lower than in western countries. Although a few young patients with type 2 AIH have been observed in South Asia, most patients in Asia are middle-aged women with type 1 AIH who respond well to steroid-based immunosuppressive therapy. Human leukocyte antigen DR4 is suggested to be an influential factor in the genetic background of AIH patients in Asia, particularly in East Asia. Notably, AIH may be induced by some societal- or culture-associated medicines, including herbal medicines. The IAIHG (International Autoimmune Hepatitis Group) scoring systems are generally accepted as the standard diagnostic methods for AIH in Asian countries. The results of repeated nationwide surveys in Japan suggest that the clinical features of AIH patients in East Asia are changing, with IgG levels and rates of anti-nuclear antibody positivity decreasing.

Cell therapy for cerebral hemorrhage: Five year follow-up report.

The aim of the study was to examine treatment of cerebral hemorrhages with bone-marrow or human umbilical cord-derived mesenchymal stem cells (BMSCs or Hu-MSCs) and conventional surgical approaches, and determine and compare the effectiveness, feasibility, safety and reproducibility of each method. A retrospective analysis was performed on a cohort of cell-treated cerebral hemorrhage patients from October 1, 2007 to October 1, 2009. A total of 24 patients, all of whom received conventional surgical treatment, were classified as follows: i) The control group consisted of 8 patients who received only hematoma removal surgery, ii) the autologous group consisted of 7 patients who received additional autologous bone marrow mononuclear cell transplantation, and iii) the allograft group consisted of 9 patients who received additional umbilical cord mononuclear cell transplantation. After conventional hematoma removal surgery and X-ray supervision within 24 h and at 7 days, neurological disability and function tests were completed 3, 6, 12, 36 and 60 months later. The T-cell marker plasma levels were analyzed after 60 months. The results showed that, at approximately 3.5 months after graft the hematomas in all the groups were completely reabsorbed as observed on computed tomography scans. However, the functional outcomes in the cell-transplanted groups were better than in the control group after 5 years. While the National Institutes of Health Stroke Scale, modified Rankin score and modified Barthel index scores were simliar in the cell-transplanted groups, patients in the allograft group had better outcomes than those in the autologous graft group starting at 3 months and until the end of the follow-up period. The serum levels of T-cell markers CD4, CD56 and human leukocyte antigen-DR in the allograft group showed no signs of immunogenic graft complications and there were no significant differences in T-cell subtypes among the patient groups. The results of the present study suggest that, treatment of cerebral hemorrhage patients can be safely and effectively accomplished using Hu-MSC grafting and larger clinical trials should be considered in the future.

The significance of the monocyte human leukocyte antigen-DR level in the assessment of the severity of acute pancreatitis / 中华危重病急救医学

Objective To investigate the clinical value of the peripheral blood monocyte human leukocyte antigen-DR (mHLA-DR) for assessment of degree of severity and the diagnosis of acute pancreatitis (AP). Methods A case-control study was conducted. Eighty-six AP patients admitted to Shandong Liaocheng People's Hospital from June 2014 to May 2015 were enrolled. Patients were classified into four groups [mild (n = 33), moderate (n = 25), severe (n = 16), critical (n = 12)] according to the disease classification. Eighty healthy persons subjected to physical examination center of our hospital at the same time were served as controls. Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores in patients were estimated. Flow cytometry was used to measure the expression of the peripheral blood mHLA-DR, and the Pearson method was used to analyze the relationship between the level of mHLA-DR and the APACHE Ⅱ score. The receiver-operating characteristic curve (ROC) was plotted, and then the clinical value of the peripheral blood mHLA-DR was analyzed for the diagnostic value in AP patients. Results The expression of the mHLA-DR in patients with AP was significantly lower than that of healthy control group [(63.7±18.6)% vs. (86.4±8.3)%, t = 5.319, P < 0.001]. The expression levels of the mHLA-DR in mild group, moderate group, severe group, and critical group were (79.6±6.5)%, (66.4±9.4)%, (49.9±8.1)%, (32.5±12.0)%, respectively, and the APACHE Ⅱ score were 4.67±1.99, 5.88±2.05, 9.06±2.62, 12.33±3.96, respectively. Pair wise comparisons were statistically significant (all P < 0.05). The HLA-DR expression level in the peripheral blood of patients with AP was negatively correlated with the APACHE Ⅱ score (r = -0.695, P < 0.001). The area under the ROC curve (AUC) of mHLA-DR expression in peripheral blood for AP was 0.894 [95% confidence interval (95%CI) = 0.847-0.941, P < 0.001], and the cut-off point was 84.40%, with the sensitivity of 75.0%, the specificity of 90.7%, and the accuracy rate of 83.1%. The AUC of mHLA-DR expression for mild AP was 0.938 (95%CI = 0.889-0.987, P < 0.001), and the cut-off point was 72.70%, with the sensitivity of 87.9%, the specificity of 88.7%, and the accuracy rate of 88.4%. The AUC of mHLA-DR expression for severe and critical AP was 0.943 (95%CI = 0.881-1.005, P < 0.001), and the cut-off point was 57.85%, with the sensitivity of 84.0%, the specificity of 96.4%, and the accuracy rate of 90.6%. Conclusions The expression levels of the peripheral blood mHLA-DR in AP patients can reflect the degree of disease, and contribute to the diagnosis of AP. The value of mHLA-DR may be used as a new biological indicator in the diagnosis and assessment for the severity of AP.

Effect of hemofiltration combined with hemoabsorption on improvement of immune function in septic patients with low expression of human leukocyte antigen DR / 中华危重病急救医学

ObjectiveTo investigate the effect on improving immune function by hemofiltration combined with hemoabsorption in septic patients with low human leukocyte antigen DR (HLA-DR) expression.Methods 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 veno-venous 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 evaluationⅡ(APACHEⅡ) score, duration of mechanical ventilation, length of intensive care unit (ICU) stay, and 28-day survival rate were evaluated in both groups.Results 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)%, allP0.05). APACHEⅡ 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, allP< 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).Conclusion 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.

Expression of CD38 and HLA -DR on CD +8 T cells in patients with chronic hepatitis B and HBV carriers / 中国基层医药

Objective To determine the expression of CD38 and HLA -DR on CD +8 T cells in patients with chronic hepatitis B and HBV carriers,and to disscuss the relation between immune activation and disease progression of HBV infection.Methods Thirty -two chronic hepatitis B patients receiving adefovir dipivoxil treatment,31 HBV carriers and 28 normal controls were collected.The counts of CD +4 and CD +8 T cells and the percentage of CD +8 CD +38 and CD +8 HLA -DR +T cells were tested by flow cytometry.HBV DNA and liver function were tested in the central laboratory of our hospital.Results The percentage of CD +8 CD +38 T cells in CHB patients was (58.4 ±12.7)%,and was higher than that in HBV carriers (46.8 ±8.5)% and normal controls (46.8 ±8.5)%,and decreased after adefovir dipivoxil treatment (34.2 ±9.4%)(F =8.27,P =0.000).The percentage of CD +8 CD +38 T cells in HBV carriers was (43.3 ±12.5)%,and was much higher than that in normal controls (9.8 ±5.7)%(F =13.48,P =0.000).The percentage of CD +8 HLA -DR + T cells in CHB patients was higher than that in normal controls,but similar to that in HBV carriers (37.1 ±11.3)%.CD +8 HLA -DR + T cells in CHB patients also decreased after adefovir dipivoxil treatment (P <0.05 ).Conclusion Our study demonstrates that activation of CD +8 T cells is increased in HBV infection but decreased by adefovir dipivoxil treatment.The percentages of CD +8 CD +38 and CD8 +HLA -DR +T are good markers for disease progression of HBV infection.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B.

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B. METHODS: Patient records at a single institution's hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed. RESULTS: The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, Pc = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site. CONCLUSION: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.