Correlation between the distribution of peripheral blood monocyte subsets and the pathogenesis of rheumatoid arthritis / 中华检验医学杂志

Objective:This work aims to assess the distribution of peripheral blood monocyte subsets, the expression level of the functional markers in rheumatoid arthritis (RA) patients, and analyze the correlation between the above indexes and the onset of RA.Methods:Peripheral blood mononuclear cells were collected and isolated from 62 RA patients, 52 healthy control (HC) and 12 disease control group′s patients via density centrifugation. The enrolled patients were attended or underwent physical examination in East Hospital, Tongji University from June 2020 to December 2021. Monocytes could be classified into classical (CM), intermediate (IM) and non-classical (NCM). Then, the flow cytometry was performed to examine the distribution of monocyte subsets and the measure the expression level of human leukocyte antigen DR (HLA-DR), intracellular tumor necrosis factor α (TNF-α) in peripheral blood monocytes. The statistical methods in this study mainly include: Kruskal-Wallis H test, Chi-Square test, Mann-Whitney U test, Wilcoxon matched-pairs signed ranks test, Spearman correlation coefficient test and Logistic regression analysis. The diagnostic value of IM proportion in RA was analyzed by ROC curve. Results:The monocytes number and monocytes proportion in white blood cells were much higher in RA [0.40 (0.40, 0.50), 7.60% (5.97%, 8.53%)] and disease control [0.40 (0.40, 0.68), 8.20% (5.85%, 10.28%)] compared with HC [0.30 (0.30, 0.40), 5.80% (5.03%, 6.38%)] ( H=24.733, P<0.001; H=27.469, P<0.001). A statistic-significant difference was detected among the proportion of CM[85.49%(76.91%,89.21%),88.94%(86.36%,91.72%),90.26%(80.25%, 92.56%)],IM[11.65%(8.47%,17.89%),7.89%(5.36%,10.75%), 5.56%(4.17%, 8.27%)], NCM[2.22%(1.39%, 3.74%), 2.49%(1.74%, 4.66%), 5.13%(3.39%, 9.85%)] in RA group, HC group and disease control group ( H=11.389, P=0.003; H=20.815, P<0.001; H=10.640, P=0.005). The proportion of CM was lower in RA and the IM proportion was increased in RA( P=0.003; P=0.003). The intracellular TNF-α level of monocytes in all three groups revealed the trend that IM>NCM>CM. The intracellular TNF-α in IM of RA was positively associated with serum TNF-α ( r=0.376, P=0.041). The HLA-DR expression in IM subsets were higher than CM and NCM subsets in all RA,HC and disease control groups. The expression of HLA-DR of IM in RA group and disease control was higher than HC group [8 611.50 (6201.3, 9890.8), 10 295.0 (7 899.0, 13632.0), 6 278.00(4 057.8, 9522.0), H=10.495, P=0.005]. There were no correlations between the proportion of peripheral blood IM and clinical characteristics CRP ( r=0.119, P=0.359), RF ( r=0.204, P=0.112) and ESR ( r=0.153, P=0.236). Logistic regression analysis showed that the proportion of IM ( OR=1.169, 95% CI 1.003-1.363, P=0.046), CRP ( OR=1.277, 95% CI 1.000-1.631, P=0.050), RF ( OR=1.179, 95% CI 1.080-1.287, P<0.001) are positively correlated with RA onset. The area under ROC curve for diagnosis of RA with IM proportion was 0.687, and the 95% confidence interval was 0.590-0.784, P<0.001. Conclusions:The distribution of monocyte subsets in peripheral blood of RA patients is abnormal. The increase in the proportion of IM, the enhanced antigen-presenting ability, and the increased level of TNF-α secretion in RA patients may play an important role in the pathogenesis of RA.

Immunoexpression of human leukocyte antigen-DR in actinic cheilitis and lower lip squamous cell carcinoma

Abstract The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.

Value of abnormal HLA-DR expression on CD14+ monocytes in estimating immune function status and clinical prognosis of patients with hand, foot and mouth disease / 中华微生物学和免疫学杂志

Objective@#To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD).@*Methods@#From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expression<30%) and normal DR group (DR-N, HLA-DR expression>30%) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14+ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plasma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score (PCIS) and the pediatric risk of mortality Ⅲ (PRISM Ⅲ) were used to estimate the severity of HFMD.@*Results@#① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F=47.102, P<0.05). Patients with critical HFMD had the lowest HLA-DR expression (P<0.05). ② The numbers of CD14+ monocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in patients with severe or critical HFMD (P<0.05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0.05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0.05). The ratio of IFN-γ/IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0.05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r=-0.704, P<0.05), and positively correlated with the IFN-γ/IL-10 ratio (r=0.773, P<0.05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively correlated with PCIS (r=0.715, P=0.00) and negatively correlated with PRISM Ⅲ (r=-0.610, P=0.00). ⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0.05).@*Conclusions@#Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14+ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14+ monocytes might be associated with severe HFMD and poor prognosis.

Value of abnormal HLA-DR expression on CD14+ monocytes in estimating immune function status and clinical prognosis of patients with hand, foot and mouth disease / 中华微生物学和免疫学杂志

Objective To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD). Methods From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expres-sion<30％ ) and normal DR group (DR-N,HLA-DR expression>30％ ) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14+ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plas-ma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score ( PCIS) and the pediatric risk of mortality Ⅲ(PRISM Ⅲ) were used to estimate the severity of HFMD. Results ① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F = 47. 102, P<0. 05). Patients with critical HFMD had the lowest HLA-DR expression (P<0. 05). ② The numbers of CD14+ monocytes, CD3+T cells, CD4+T cells, CD8+T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in pa-tients with severe or critical HFMD (P<0. 05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0. 05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0. 05). The ratio of IFN-γ/ IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0. 05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r= -0. 704, P<0. 05), and positively correlated with the IFN-γ/ IL-10 ratio (r = 0. 773, P<0. 05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively corre-lated with PCIS (r=0. 715, P=0. 00) and negatively correlated with PRISM Ⅲ (r = -0. 610, P = 0. 00).⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0. 05).Conclusions Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14+ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14+ monocytes might be associated with severe HFMD and poor prognosis.

Effects of Shenmai injection combined with enteral nutrition on immune function of patients with severe cardiac insufficiency / 中国中西医结合急救杂志

Objective To observe the effect of Shenmai injection combined with enteral nutrition (EN) on immune function in patients with severe cardiac insufficiency. Methods Fifty-seven patients with severe cardiac insufficiency admitted to the Department of Critical Care Medicine of Taizhou Hospital of Zhejiang Province from June 2015 to June 2018 were divided into an EN group (31 cases) and an EN group combined with Shenmai injection group (26 cases). The EN group was given EN on the basis of routine western medicine treatment, while in the EN combined with Shenmai injection group was treated additionally by intravenous drip of Shenmai injection 100 mL/d on the basis of above EN group treatment. The efficacies of the two groups were evaluated after consecutive 7-day treatment in the two groups. The changes in levels of subsets of T-lymphocytes (CD3+, CD4+, CD8+, CD4+/CD8+) and immunosuppressive cells CD14+ monocyte human leukocyte antigen DR (HLA-DR) were observed before and after treatment. Results After treatment, the levels of T-cell subsets CD3+, CD4+, CD4+/CD8+ and CD14+ monocytes HLA-DR in the peripheral blood of the two groups were significantly higher than those before treatment [CD3+: EN group was 0.539±0.126 vs. 0.379±0.093,Shenmai injection group was 0.652±0.185 vs. 0.393±0.091; CD4+: EN group was 0.402±0.121 vs. 0.275±0.066,Shenmai injection group was 0.524±0.168 vs. 0.281±0.077; CD4+/CD8+:EN group was 1.83±0.70 vs. 1.11±0.70,Shenmai injection group was 2.81±0.91 vs. 1.19±0.58; CD14+HLA-DR:EN group was (43.3±7.1)% vs. (35.4±5.7)%,Shenmai injection group was (54.9±6.2)% vs. (36.1±8.3)%]; After treatment, CD8+ in EN group decreased (0.223±0.052 vs. 0.253±0.081), while CD8+ in shenmai injection group increased (0.288±0.051 vs. 0.259±0.078), and the increase degrees of the above-mentioned indexes in EN combined with Shenmai injection group were more obvious than those in the EN group after treatment [CD3+: 0.652±0.185 vs. 0.539±0.126, CD4+: 0.524±0.168 vs. 0.402±0.121, CD8+: 0.288±0.051 vs. 0.223±0.052, CD4+/CD8+: 2.81±0.91 vs. 1.83±0.70, CD14+HLA-DR: (54.9±6.2)%, (43.3±7.1)%, all P < 0.05]. Conclusion The combined use of Shenmai injection and early EN can improve the immune function of T-lymphocytes in patients with severe cardiac insufficiency. The mechanism may be related to the enhancement of the activation of T lymphocytes and promotion of the CD14+ monocytes increase and immune function.

Role of human leukocyte antigen-DR expression on predicting the prognosis of hepatocellular carcinoma / 国际肿瘤学杂志

Objective To explore the expression of human leukocyte antigen-DR (HLA-DR) in hepatocellular carcinoma and its clinical values in predicting prognosis.Methods The primary hepatocellular carcinoma tissues of 97 patients in our hospital from August 2012 to February 2014 were enrolled as subjects (case group),and the adjacent normal liver tissues were selected as control (control group,n =97).The expressions of HLA-DR in the two groups were detected by immunohistochemistry,and the relationships between HLA-DR expression and chnicopathological features,recurrence and prognosis were analyzed.Results The positive expression rate of HLA-DR in specimens of case group was 55.67％,which was higher than 21.65％ in comrol group,and the difference was statistically significant (x2 =23.671,P ＜ 0.001).The positive expression rates of HLA-DR in tumor tissues with diameter ≥4 cm,Ⅲ-Ⅳ stage,poorly differentiated,bile duct cell carcinoma,no lymph node metastasis were higher than those in tumor tissues with diameter ＜4 cm,Ⅰ-Ⅱ stage,medium and well differentiated,hepatocellular carcinoma,lymph node metastasis respectively,and the differences were statistically significant (x2=10.481,P =0.001;x2=18.854,P ＜ 0.001;x2 =9.876,P =0.002;x2 =6.834,P =0.009;x2=30.668,P ＜ 0.001).The recurrence rates of 2 years and 3 years were 27.91％ and 46.51％ in patients with negative expression of HLA-DR respectively,which were lower than 50.00％ and 70.37％ in patients with positive expression of HLA-DR respectively,and the differences were statistically significant (x2 =4.860,P =0.028;x2 =5.668,P =0.017).The median survival time of patients with HLA-DR positive expression was 33.64 months,which was shorter than 36.88 months in patients with negative expression,and the difference was statistically significant (x2 =10.356,P ＜ 0.001).TNM staging Ⅲ-Ⅳ (OR =0.899,95 ％ CI:0.721-0.995,P =0.012) and positive expression of HLA-DR (OR =1.125,95％ CI:1.025-2.568,P =0.018) were unfavorable to the prognosis of hepatocellular carcinoma patients.Conclusion HLA-DR expresses abnormally in patients with primary hepatocellular carcinoma,which may be involved in the occurrence and development of hepatocellular carcinoma,and the up-regulation of HLA-DR in patients with hepatocellular carcinoma indicates a high recurrence rate and short survival time.

Association between HLA-DR Expression and Multidrug-resistant Infection in Patients with Severe Acute Pancreatitis / 华中科技大学学报（医学）（英德文版）

Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.

Association between HLA-DR Expression and Multidrug-resistant Infection in Patients with Severe Acute Pancreatitis / 华中科技大学学报（医学）（英德文版）

Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.

Association of and Polymorphisms with Risk of Systemic Lupus Erythematosus / 中华医学杂志(英文版)

Background@#Systemic lupus erythematosus (SLE) is an autoimmune disease under genetic control. Growing evidences support the genetic predisposition of HLA-DRB1 gene polymorphisms to SLE, yet the results are not often reproducible. The purpose of this study was to assess the association of two polymorphisms of HLA-DRB1 gene (HLA-DR3 and HLA-DR15) with the risk of SLE via a comprehensive meta-analysis.@*Methods@#This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case-control studies on HLA-DRB1 and SLE were searched from PubMed, Elsevier Science, Springer Link, Medline, and Cochrane Library database as of June 2018. Analysis was based on the random-effects model using STATA software version 14.0.@*Results@#A total of 23 studies were retained for analysis, including 5261 cases and 9838 controls. Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]: 1.60, 95% confidence interval (CI): 1.316-1.934, P = 0.129 and OR: 1.68, 95% CI: 1.334-2.112, P = 0.001, respectively). Subgroup analyses demonstrated that for both HLA-DR3 and HLA-DR15 polymorphisms, ethnicity was a possible source of heterogeneity. Specifically, HLA-DR3 polymorphism was not associated with SLE in White populations (OR: 1.60, 95% CI: 1.320-1.960, P = 0.522) and HLA-DR15 polymorphism in East Asian populations (OR: 1.65, 95% CI: 1.248-2.173, P = 0.001). In addition, source of control was another possible source for both HLA-DR3 and HLA-DR15 polymorphisms, with observable significance for HLA-DR3 in only population-based studies (OR: 1.65, 95% CI: 1.370-1.990, P = 0.244) and for HLA-DR15 in both population-based and hospital-based studies (OR: 1.38, 95% CI: 1.078-1.760, P = 0.123 and OR: 2.08, 95% CI: 1.738-2.490, P = 0.881, respectively).@*Conclusions@#HLA-DRB1 gene may be a SLE-susceptibility gene, and it shows evident ethnic heterogeneity. Further prospective validations across multiple ethnical groups are warranted.

Human leukocyte antigen HLADRB1 determinants susceptibility to gastroesophageal reflux disease / Antígeno leucocitário humano HLADRB1 é determinante de susceptibilidade para a doença do refluxo

ABSTRACT BACKGROUND Gastroesophageal reflux disease (GERD) is characterized by diverse symptoms. There is an evidence for a genetic component to GERD as supported by familial aggregation of this disease. OBJECTIVE To investigate whether certain human leucocyte antigen genes HLA-DRB1 are associated with GERD. METHODS Patients and controls were prospectively recruited from GIT center at Al-Kindy Teaching Hospital (Baghdad-Iraq) between January 2014 and July 2016. Sixty Iraqi Arab Muslims patients with a history of heartburn and dyspepsia compared with 100 Iraqi Arab Muslims controls. All study patients and control groups underwent upper gastrointestinal endoscopic examinations and their serums were analyzed for CagA antibodies Immunoglobulin G (IgG) for H. pylori. HLA-DRB1 genotyping were done to both groups. RESULTS A total of 60 patients with erosive gastritis; GERD (Grade II and III) were evaluated, together with 100 controls. There is a significant increase of H. pylori infection (P=0.0001) in GERD patients than control group. HLA-DRB1* 15:01 was significantly increased in GERD patients in comparison with control group and an increased frequency of HLADRB1*11:01 in control group compared with patients group. CONCLUSION There is an association between HLA-DRB1 *15:01 in GERD patients with H. pylori positive patients.

RESUMO CONTEXTO A doença do refluxo gastroesofágico (DRGE) caracteriza-se por diversos sintomas. Há evidências de um componente genético para a doença de refluxo suportado pela agregação familiar desta doença. OBJETIVO Investigar se certos genes de antígeno de leucócito humano HLA-DRB1 são associados à DRGE. MÉTODOS Pacientes e indivíduos controles foram recrutados prospectivamente do centro GIT no Al-Kindy Hospital (Bagdá-Iraque) entre de 2014 janeiro e julho de 2016. Sessenta pacientes muçulmanos árabes iraquianos com uma história de azia e dispepsia foram comparados com 100 indivíduos controles. Todos os pacientes do estudo e grupos de controle foram submetidos a exames de endoscopia gastrointestinal alta e seus soros foram analisados para anticorpos CagA imunoglobulina G (IgG) para H. pylori. Genotipagem HLA-DRB1 foram feitas para ambos os grupos. RESULTADOS Um total de 60 pacientes com gastrite erosiva; GERD (grau II e III) foram avaliados, em conjunto com 100 controles. Houve aumento significativo de infecção pelo H. pylori (P=0,0001) em pacientes com DRGE em relação ao grupo controle. O HLA-DRB1* 15:01 aumentou significativamente em pacientes com DRGE em comparação com o grupo controle e houve uma maior frequência de HLADRB1* 11:01 no grupo controle em comparação com o grupo de pacientes com DRGE. CONCLUSÃO Há uma associação entre HLA-DRB1* 15:01 em pacientes com DRGE positivos para a infecção por H. pylori.

Adiponectin inhibits oxidization-induced differentiation of T helper cells through inhibiting costimulatory CD40 and CD80

Adiponectin is a multifunctional adipokine that has several oligomeric forms in the blood stream, which broadly regulates innate and acquired immunity. Therefore, in this study, we aimed to observe the differentiation of T helper (Th) cells and expression of costimulatory signaling molecules affected by adiponectin. The mRNA and protein expression levels of adiponectin and its receptors in oxidized low density lipoprotein cholesterol-treated endothelial cells were assayed by real time PCR and immunofluorescence. The endothelial cells were then treated with adiponectin with or without adipoR1 or adipoR2 siRNA and co-cultured with T lymphocytes. The distribution of Th1, Th2 and Th17 subsets were assayed by flow cytometry. The effects of adiponectin on costimulatory signaling molecules HLA-DR, CD80, CD86 and CD 40 was also assayed by flow cytometry. The results showed that endothelial cells expressed adiponectin and its receptor adipoR1 and adipoR2, but not T-cadherin. Adiponectin suppressed Th1 and Th17 differentiation through adipoR1 receptor, contributed to the inhibition of CD80 and CD40, and inhibited differentiation of Th1 and Th17 by inhibiting antigen presenting action.

Diagnostic Value and Significance of the HLA-DR53,Anti-Sa and Anti-CCP Antibody Factors Combination in Rheumatoid Arthritis / 现代检验医学杂志

Objective To explore the value of human leucocyte antigen-DR53 (HLA-DR53),anti-Sa antibody and anti-cyclic citrullinated peptide antibody(anti-CCP) factors combination in rheumatoid arthritis.Methods 170 patients with rheumatoid arthritis and 50 healthy individuals in the hospital were chosen.The levels of HLA-DR53 by PCR-SSP,the levels of anti-Sa and anti-CCP by ELISA,compared their diagnostic value by consistency analysis and joint detection analysis.Results The sensibility of anti-Sa,HLA-DR53 and anti-CCP in RA were 44.07％ (P =0.00,x2 =165.214),68.65 ％ (P =0.00,x2 =9.837) and 79.45 ％ (P=0.00,x2=48.028).Consistency analysis in RA,HLA DR53,anti-CCP and anti-Sa highly consistent,OR were 3.94,38.6 and 184.52.The sensitivity and Youden index of anti-CCP were the highest.The sensitivity of anti Sa and anti-CCP parallelled was 88.51 ％.The sensitivity of HLA-DR53 and anti-CCP parallelled was 93.56％,and the spe cificity of anti-Sa and anti-CCP of RA were 100％.Conclusion There is a certain correlation between HLA-DR53,anti-Sa and anti-CCP antibody,which are related risk factors of RA,co-detection will improve the diagnosis of RA.

Frequency and Distinct Characteristics of Acute Myeloid Leukemia Lacking HLA-DR and CD34 Expression: Features Intermediate between Typical Acute Myeloid Leukemia and Acute Promyelocytic Leukemia

BACKGROUND: The objective of this study was to investigate the frequency and characteristics of HLA-DR⁻/CD34⁻ acute myeloid leukemia (AML) also known as acute promyelocytic leukemia (APL)-like AML. METHODS: This study included 683 newly diagnosed patients with AML. After exclusion of 211 patients with recurrent genetic abnormalities, one with acute panmyelosis with myelofibrosis, two with myeloid leukemia associated with Down syndrome, and two devoid of metaphase cells, we classified the remaining 467 patients as follows: group 1, HLA-DR⁺/CD34⁺ (typical AML); group 2, HLA-DR⁺/CD34⁻ or HLA-DR⁻/CD34⁺; group 3, APL-like AML. RESULTS: Group 1 comprised 294 patients, group 2 comprised 133, and group 3 comprised 40. Therefore, the frequency of APL-like AML among 683 unselected patients with AML was 5.9%. Group 3 patients had significantly higher leukocyte counts and bone marrow (BM) blast percentages, higher frequencies of normal karyotypes and NPM1 mutation, higher fractions of CD33-positive cells, higher concentrations of fibrin degradation products and D-dimers, lower frequencies of complex karyotypes, monosomal karyotypes and poor cytogenetic risk, lower fractions of CD13-positive cells, and lower fibrinogen concentrations, compared with group 1 patients. The values of the BM blast percentage, number of CD33-positive cells, and DIC score of the patients with APL-like AML were intermediate between those of the patients with typical AML and APL. CONCLUSIONS: This study demonstrates that APL-like AML is not uncommon, and it has characteristics distinguishable from those of typical AML. APL-like AML may have some pathophysiological relationships with APL, which need further investigation.

Autoimmune Hepatitis: Varied Clinical Manifestations in a Tertiary Care Centre.

Autoimmune hepatitis is defined as chronic liver disease of unknown aetiology with aberrant auto-reactivity and genetic predisposition, characterized by female predominance, circulating auto-antibodies, hypergammaglobulinemia and association with HLA DR3 and HLA DR4. We present two patients with autoimmune hepatitis. The first patient is a young lady who was diagnosed with autoimmune chronic hepatitis. The second patient, on the other hand, is an elderly gentleman who presented to us with autoimmune hepatitis related decompensated cirrhosis of liver.

HLA-DR3 antigen in the resistance to idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC.

Comparative study of laparoscopic and transabdominal radical hysterectomy's impact on the cellular immunity / 中国内镜杂志

Objective To compare the difference of impact on the cellular immunity between laparoscopic and transabdominal radical hysterectomy. Methods 60 patients with early cervical cancer (Ⅰa2~Ⅱa1), half of them were assigned to do abdominal radical hysterectomy (ARH) and the other half for laparoscopic radical hysterectomy (LRH). Adopt flow cytometry (FCM) detect peripheral blood T lymphocyte subsets, NK cells, CIK cells and T lymphocyte ac-tivation function on one day before surgery, one day, five days, and 28 days after the surgery separately. Compare the changes of immune status. Results After one day, the number of T lymphocyte subsets declined compared with preoperative one day(P <0.05). After five days, each index in LRH group was increased compared with postoperative one day, and the degree of decline is less than the ARH group ( P< 0.05), and recovered faster. After one day, the number of HLA-DR+CD3+in LRH group compared with the preoperative one day declined and HLA-DR+CD8+in-creased, and the degree of change is less than the ARH group, and recovered faster. Conclusions Immune function in patients after laparoscopic group was less changed, and recovered quickly, while the immune function were less inhibited, it may protect patients' immune function better.

A study on HLA-DR/DQ typing in adult Malay patients with acute amoebic liver abscess

Introduction: Amoebiasis is a parasitic disease caused by Entamoeba histolytica that may lead to death in developing countries. Few important risk factors have been identified in the development of amoebic liver abscess (ALA). There are limited reports that suggest an association between antigens of the major histocompatibility complex (MHC) particularly class II antigens and ALA development. This present work aimed at studying the possible association of HLA antigens with ALA and disease severity. Results of the study may serve as a guide for further immunological studies dealing with E. histolytica. Methods: This preliminary study involved two groups of subjects: 20 ALA patients in the experimental group and 40 healthy individuals in the control group. Cases were selected from adult Malay patients confirmed with ALA based on clinical signs and symptoms, radiological findings, microbiological findings and who were admitted to the medical or surgical ward, Hospital USM, Kelantan. Venous blood was obtained from each patient and HLA typing was then conducted using polymerase chain reaction specific primer sequence. Results: HLA DR12 was most frequently found in the healthy control and ALA groups at 40% and 55% respectively. HLA DQ7 and DQ8 were found to have the highest percentage in the ALA group at 65%. In the control group, HLA DQ8 (57.5%) had the highest percentage. Conclusion: HLA antigens play a role in acquisition of ALA and provide understanding of the disease outcome.

Predictive analysis for prognosis of CD14+ monocyte HLA-DR in geriatric trauma patients / 解放军医学杂志

Object To evaluate the prognostic roles of HLA-DR+/CD14+ expression rate in peripheral blood monocytes in geriatric trauma sepsis. Methods A retrospective study of clinical data was carried out. Clinical data of geriatric trauma patients (age≥60 years) admitted to intensive care unit (ICU) of Guangzhou General Hospital of Guangzhou Command from January 2011 to December 2015 were collected. The expressions of HLA-DR+/CD14+, procalcitonin (PCT) and C-reactive protein (CRP) were detected within 24 hours after admission. Spearman correlation analysis was adopted to analyze the correlation between the HLADR+/CD14+ and the length of ICU stay, and between the length of stay and APACHE II. Receiver operating characteristic (ROC) curve was used to evaluate the prognostic roles of HLA-DR+/CD14+ expression, PCT, CRP and APACHE II score. Results There were significant differences between survivors and nonsurvivors in APACHE II score (17.49 6.25 vs 27.38 8.68, P<0.05) and the expressions of HLA-DR+/CD14+ (59.80 18.02 vs 37.70 13.96, P<0.01). There were significant differences between sepsis and non-sepsis in APACHE II score (26.16 8.44 vs 17.90 7.04, P<0.01) and the expressions of HLA-DR+/CD14+ (38.61 14.48 vs 59.79 18.17, P<0.01), PCT (34.45 68.29 vs 4.25 8.26, P<0.01) and CRP (129.88 103.25 vs 76.04 73.48, P<0.011). There existed a negative relationship between the HLA-DR+/CD14+ and length of ICU stay (r=-0.304, P=0.008), and APACHE (r=-0.559, P=0.000). There was no significant relationship between the HLA-DR+/CD14+ and length of stay (r=0.188, P=0.106). By ROC for sepsis prognosis, the area under the curve (Mean SE) of HLA-DR+/CD14+ was 0.807 0.051 (95%CI 0.706-0.907, P=0.000), the AU-ROC (Mean SE) of PCT was 0.714 0.063 (95% CI: 0.591-0.837, P=0.003). The best cut-off for HLA-DR+/CD14+ was 40%, with the sensitivity of 88.0% and specificity of 60.0%.The best cut-off for PCT was 1.01, with the sensitivity of 84.0% and specificity of 65.0%. By ROC curve analysis for prognosis, the AU-ROC (Mean SE) of HLA-DR+/CD14+ and APACHE II were 0.813 0.049 (95%CI 0.716-0.910, P=0.00) and 0.825 0.052 (95% CI 0.724-0.926, P=0.000), respectively. The best cut-off for HLA-DR+/CD14+ was 36.0%, with the sensitivity of 94.1% and specificity of 50.0%. The best cut-off for APACHE II was 20, with the sensitivity of 80.1% and specificity of 65.0%. Conclusion Low expression of HLA-DR+/CD14+ indicates hypoimmunity of geriatric trauma patients, and can play an significant role in predicting development of sepsis and poor prognosis.

Effects of Shenfu injection combined with low-dose hydrocortisone on plasma levels of HLA-DR and PCT in patients with septic multiple organ dysfunction syndrome / 天津医药

Objective To explore the effects of Shenfu injection combined with low-dose hydrocortisone on plasma lev?els of human leukocyte antigen (HLA)-DR and procalcitonin (PCT) in patients with septic multiple organ dysfunction syn?drome. Methods A total of 118 patients with septic multiple organ dysfunction syndrome were divided into three groups:control group (n=39), experimental group 1 (n=39) and experimental group 2 (n=40). The control group received conventioanl medicine therapy, while the experimental group 1 received Shenfu injection (100 mL, 2/d, for 7 d) combined with conventio?anl medicine therapy, and the experimental group 2 received Shenfu injection combined with low-dose hydrocortisone (200 mg/d, for 14 d) besides conventional medicine therapy. The peripheral blood samples were collected for the detection of HLA-DR, PCT and lipoperoxide (LPO) before treatment, 1 d, 3 d amd 7 d after treatment. The mortality in 14 d was record?ed. Results The mortality rates in 14 d were 61.5%(24/39), 41.0%(16/39) and 25.0%(10/40) for control group, experimen?tal group 1 and experimental group 2 (χ2=8.15, P0.05). The plasma levels of PCT and LPO were significantly decreased in control group, experimental group 1 and experimental group 2 after 3-d and 7-d treatment, but the levels of HLA-DR was significantly increased (P < 0.05). Conclusion The combination therapy of Shenfu injection and low-dose hydrocortisone can effectively reduce PCT level and increase HLA-DR level, which promotes the improve?ment of patients with septic multiple organ dysfunction syndrome.