Expression of human leukocyte antigen-G in systemic lupus erythematosus

The purpose of this study was to examine the expression of human leukocyte antigen-G (HLA-G) in patients with systemic lupus erythematosus (SLE) and its relation with interleukin-10 (IL-10) production. The study included 50 female SLE patients and 59 healthy female donors. HLA-G expression in peripheral blood and cutaneous biopsies was determined by flow cytometry and immunohistochemistry, respectively. Soluble HLA-G (sHLA-G) and IL-10 were quantified in serum samples by enzyme-linked immunosorbent assay. SLE patients presented with serum sHLA-G and IL-10 levels significantly higher than that observed in controls (median [interquartile range (IQR)] = 43.6 U/ml [23.2-150.2] vs 26.84 U/ml [6.0-45.2], p = 0.004; and 1.4 pg/ml [0-2.3] vs 0 pg/ml [0-1.5], p = 0.01, respectively). But no correlation was observed between sHLA-G and both IL-10 levels and the disease activity index for SLE patients. The expression of membrane HLA-G in peripheral lymphocytes from SLE patients was low, but higher than in controls (median [IQR] = 1.5% [0.6-1.8] and 0.3% [0.2-0.8], respectively; p = 0.02). Finally, these findings were in accordance with the weak expression of HLA-G in skin biopsies. Despite the fact that patients present higher levels of HLA-G than healthy controls, which suggests a possible relevance of this molecule in SLE, it seems not to be related to IL-10 production or disease activity.     

Elevation of human leukocyte antigen-G expression is associated with the severe encephalitis associated with neurogenic pulmonary edema caused by Enterovirus 71

Enterovirus 71 (EV71) infection can develop devastating clinical outcomes such as brain stem encephalitis (BE) and pulmonary edema (PE). Alteration of human leukocyte antigen-G (HLA-G) expression or cytokine production was considered playing important roles in virus-related pathogenesis. However, clinical relevance of HLA-G in EV71 infection remains unknown. In the current study, patients were stratified by disease severity as BE (n = 107) and PE (n = 18). HLA-G expression on peripheral blood monocytes from patients with BE (n = 15), patients with PE (n = 15) and control subjects (n = 31) was analyzed with flow cytometry. Plasma soluble HLA-G (sHLA-G) (in 67 BE, 18 PE and 120 control subjects), IL-6 and IL-10 (in 50 patients with BE, 18 patients with PE and 45 control subjects) were determined with enzyme-linked immunosorbent assay. Data showed that the percentage of HLA-G-positive monocytes (mean 7.76 vs 3.68 %, p < 0.001), levels for sHLA-G (median 129.2 vs 70.6 U/ml, p < 0.001), IL-10 (median 160.5 vs 29.5 pg/ml, p < 0.001) and IL-6 (median 20.50 vs 5.21 pg/ml, p = 0.002) was significantly higher in patients with PE than in patients with BE. Taken together, our findings indicated that elevation of HLA-G expression on monocytes, plasma sHLA-G, IL-10 and IL-6 levels was associated with PE in patients infected with EV71.     

Elevated Serum Levels of IL-10 and IFN-γ in Patients with Acute Plasmodium falciparum Malaria

Serum levels of interleukin-10 (IL-10) and interferon-γ (IFN-γ) were determined in 37 patients with acute Plasmodium falciparum malaria in Bangkok, Thailand. Serum levels of IL-10 and IFN-γ were markedly elevated in patients with malaria prior to treatment (717 ± 260 pg/ml versus 2.2 ± 1.3 pg/ml in healthy controls; 123 ± 71 pg/ml versus 29 ± 9 pg/ml, respectively; mean ± SD). Serum levels of IFN-γ and IL-10 dropped significantly during treatment and were normal 14 and 21 days, respectively, after treatment was started. Prior to therapy a correlation between serum levels of IFN-γ and IL-10 existed (r = 0.563). These results suggest that stimulatory and inhibitory cytokines for macrophage activation and/or antibody production (i.e., TH1- and TH2-type immunoreaction, respectively) are coexpressed during acute P. falciparum infection and stress the multifactorial network between host and parasite in malaria immunology.     

Evaluation of Th1/Th2 cytokines as a rapid diagnostic tool for severe infection in paediatric haematology/oncology patients by the use of cytometric bead array technology

Haematology/oncology children are usually at risk for various infections after intensive chemotherapy. We evaluated the quantification of Th1/Th2 cytokines with a flow cytometric bead array (CBA) in 795 hospitalized haematology/oncology children (309 febrile and 486 afebrile patients) to seek for a diagnostic method for determination of the type and the severity of infection. Three hundred and nine febrile patients developed a total of 505 febrile episodes. Microbiological examination demonstrated a positive blood culture (microbiologically documented infection (MDI)) in 145/505 febrile episodes. The controls included 550 healthy children, 43 haemophagocytic lymphohistiocytosis (HLH) patients, 35 cytomegalovirus infection patients and 19 Epstein–Barr virus infection patients. Interleukin (IL)-4, IL-6, IL-10, tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in febrile episodes were significantly higher than those in healthy children, and the cytokine profile was different from that of the HLH controls or the viral infection controls. IL-6 levels were much higher in MDI patients (usually >1000.0 pg/mL, 60/145) than in HLH patients (2/43); however, IFN-γ levels were only slightly increased in MDI patients, rarely being more than 100.0 pg/mL (8/145 vs. 39/43 in HLH patients). The median levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in febrile patients before antibiotic therapy were 3.9, 660.1, 122.7, 6.9 and 11.4 pg/mL, respectively, and returned to 3.3, 22.8, 9.6, 4.1 and 6.4 pg/mL, respectively, after infection was controlled. IL-6 and IL-10 levels were positively associated with septic shock and mortality rates. In conclusion, our results have demonstrated the usefulness of IL-6/IL-10/TNF-α/IFN-γ determination with CBA technology for the early rapid diagnosis, severity evaluation and assessment of therapy effect in febrile haematology/oncology children.     

Defective production of soluble HLA-G molecules by peripheral blood monocytes in patients with asthma

BACKGROUND: HLA-G, a human nonclassic MHC class I molecule, is responsible for complex immunoinhibitory functions. HLA-G is expressed as membrane-bound and is secreted as soluble molecules by the peripheral blood CD14+ monocytes activated by IL-10. OBJECTIVE: It has been reported that LPS stimulation induces IL-10 production by PBMCs and that IL-10 levels are reduced in patients with severe asthma compared with patients with mild asthma and healthy subjects. The study was designed to investigate whether this impaired IL-10 production can affect the expression and the secretion of soluble HLA-G (sHLA-G)-1/HLA-G5 molecules. METHODS: We investigated the production of sHLA-G1/HLA-G5 and IL-10 by specific ELISAs in the culture supernatants of LPS-activated PBMCs from 24 healthy subjects and 20 patients with moderate to severe persistent asthma. RESULTS: LPS stimulation induced the secretion of IL-10 and sHLA-G1/HLA-G5 molecules in all healthy subjects, whereas in patients with asthma, the levels of IL-10 were significantly lower (P < .001) and the number of cultures exhibiting detectable sHLA-G1/HLA-G5 was reduced (7/20; P < .001). The addition of exogenous IL-10 to LPS-stimulated PBMCs from patients with asthma restored normal sHLA-G1/HLA-G5 production. CONCLUSION: Our data suggest that a specific deficit of IL-10 secretion in patients with asthma could prevent the normal production of sHLA-G1/HLA-G5 molecules. The reduction of immunosuppressive activity mediated by HLA-G could in turn contribute to the persistence of chronic airway inflammation in asthma.     

Human leukocyte antigen G is associated with esophageal squamous cell carcinoma progression and poor prognosis

Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule thought to play a key role in maternal-fetal tolerance and cancer immune evasion. This study aimed to investigate the HLA-G expression in lesion sections and plasma sHLA-G levels of primary esophageal squamous cell carcinoma (ESCC) patients and its clinical significance in diagnosis and prognosis of ESCC. 60 ESCC patients and 28 healthy controls were recruited, and the positive expression of HLA-G in ESCC lesions and adjacent normal tissues were 70% (42/60) and 8.6% (5/60) (P < 0.05), respectively, while no expression was found in normal controls. HLA-G1 and HLA-G5 were determined to be dominating isoforms measured by RT-PCR. There was a significant difference in plasma sHLA-G levels between patients with ESCC (15.04 U/ml, range 4.33–250.00 U/ml) and healthy controls (6.81 U/ml, range 0–29.27 U/ml) (P < 0.01). The plasma IL-10 level was higher in ESCC patients than the controls (23.86 pg/ml vs. 12.81 pg/ml, P < 0.01). HLA-G expression in lesion tissues was correlated with cancer cell differentiation (P = 0.033), lymph node metastasis (P = 0.035) of ESCC. However, no obvious correlations were demonstrated between the plasma sHLA-G levels and the clinicopathological parameters. There was a significant correlation between sHLA-G and IL-10 expression (r = 0.353, P = 0.006) in patients with Esophageal squamous cell carcinoma. HLA-G positive expression showed poorer prognosis of ESCC. HLA-G positive expression might serve as a potential marker in the diagnosis or prediction of ESCC.     

Combined impact of hepatitis C virus genotype 1 and interleukin-6 and tumor necrosis factor-α polymorphisms on serum levels of pro-inflammatory cytokines in Brazilian HCV-infected patients

We investigated the association between hepatitis C virus (HCV) genotypes and host cytokine gene polymorphisms and serum cytokine levels in patients with chronic hepatitis C. Serum IL-6, TNF-α, IL-2, IFN-γ, IL-4, IL-10, and IL-17A levels were measured in 67 HCV patients (68.2% genotype 1 [G1]) and 47 healthy controls. The HCV patients had higher IL-6, IL-2, IFN-γ, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-γ levels than G2 patients. The -174IL6G>C, -308TNFαG>A, and -1082IL10A>G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-γ levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNFαGG genotype had higher IL-17A levels than patients with the AG genotype, whereas patients with the -1082IL10GG variant had higher IL-6 levels than patients with the AA and AG variants. A significant proportion of HCV patients had high levels of both IL-2 and IFN-γ. The subgroup of HCV patients with the G1/IL6CG/TNFαGG association displayed the highest proportions of high producers of IL-2 and IFN-γ whereas the subgroup with the G1/TNFαGG profile showed high proportions of high producers of IL-6 and IL-17A. HCV patients with other HCV/cytokine genotype associations showed no particular cytokine profile. Our results suggest that HCV genotype G1 and IL-6 and TNF-α polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-γ) in HCV patients.     

慢性丙型肝炎患者血清细胞因子水平的变化及意义

目的:检测慢性丙型肝炎患者血清细胞因子IL-2、IFN-г、IL-5、IL-6、IL-12P70和P40水平,探讨其与患者血清ALT水平、HVC RNA载量、HCV基因型及干扰素疗效的关系。方法:检测30例健康对照者和30例慢性丙型肝炎患者干扰素治疗前后血清IL-2、IFN-г、IL-5、IL-6、IL-12P70和P40的含量,比较干扰素治疗应答组和无应答组之间细胞因子水平的差异及上述细胞因子水平与血清ALT水平、HCV基因型、HCVRNA载量等的关系。血清细胞因子检测应用ELISA法,HCV基因分型应用直接测序法,HCVRNA载量采用荧光定量PCR法。结果:与健康对照组相比,慢性丙型肝炎患者血清IL-2含量明显降低,IL-5和IL-12P40明显生高;血清IL-6含量与血清ALT水平呈正相关,与RNA载量呈负相关;HCV基因型1型患者血清IL-6含量明显高于2型,其他基因型和亚型之间细胞因子水平均无显著性差异;干扰素治疗的持续应答率为46.7%,应答组和无应答组治疗前血清细胞因子水平均无显著性差异,但应答组治疗结束时IFN-γ含量较治疗前明显升高。结论:血清Th1/Th2细胞因子水平失衡与丙型肝炎的慢性化和肝脏炎症活动相关;干扰素治疗前血清Th1/Th2细胞因子水平与干扰素治疗效果无关,不能对疗效进行预测,干扰素诱导的Th1细胞优势反应与持续应答有关。     

恶性淋巴瘤患者TH 1/TH 2细胞因子表达水平的研究

目的 探讨恶性淋巴瘤患者血清中TH1/TH2细胞因子变化及其临床意义,为肿瘤的免疫治疗提供实验依据.方法 用流式细胞小球微阵列术(cytometric bead array,CBA)检测92例恶性淋巴瘤患者及70例健康人群血清中γ干扰素(IFN-γ)、肿瘤坏死因子-α仪(TNF-α)、白细胞介素(IL-2、IL-4、IL-5、IL-10)表达水平.结果 92例恶性淋巴瘤患者血清中TH1型细胞因子的水平分别为:IFN-γ(34.26±33.4g)pg/ml、TNF-α(8.17±10.09)pg/ml、IL-2(3.74 4±1.72)pg/ml;TH2型细胞因子的水平分别为:IL-10(6.28±8.56)pg/ml、IL-5(3.53±3.20)pg/ml、IL-4(6.22±7.13)pg/ml.除TNF-α表达水平降低外,其余5项均明显高于健康体检组,差异有统计学意义(P＜0.01).TH1细胞因子IL-2与TH2细胞因子IL-4的比值明显下降(0.78±O.44),与健康体检组(1.09±0.45)比较差异有统计学意义(P＜0.01).IL-10与疾病的进展相关,Ⅲ/Ⅳ期恶性淋巴瘤患者的表达水平为(9.58±13.96)pg/ml,Ⅰ/Ⅱ期的表达水平为(4.77±3.50)pg/ml,二者比较差异有统计学意义(P＜0.01).IFN-γ在大于60岁的恶性淋巴瘤患者中表达水平明显降低,与其他年龄段恶性淋巴瘤患者比较差异有统计学意义(P ＜0.05).结论 恶性淋巴瘤患者血清中TH1/TH2细胞因子平衡失调,检测TH1/TH2细胞因子可作为评价淋巴瘤临床进展及预后指标.TH1/TH2平衡向TH2方向漂移,这可能是肿瘤细胞发生免疫逃逸,从而导致肿瘤的发生或者转移的原因之一.     

Twelve potential fibrosis markers to differentiate mild liver fibrosis from cirrhosis in patients infected with chronic hepatitis C genotype 1

Information about the stage of liver fibrosis is important for managing patients with chronic hepatitis C (CHC). The aim of this study was to evaluate 12 plasma markers for differentiating no/mild liver fibrosis from cirrhosis among patients with CHC genotype 1. Transient elastography was used to assess the stage of fibrosis for the patients included in the study. Forty patients were included (21 cirrhotic). Plasma levels of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), interferon-γ inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), soluble urokinase-type plasminogen activator (suPAR), monokine induced by γ-interferon (MIG), human hepatocyte growth factor (HGF), insulin, interleukin 6 (IL-6), interleukin 1-β (IL-1β), leptin, and nerve growth factor (NGF) were analyzed. Concentrations of TNF-α (median 15.0 vs. 25.1 pg/ml, area under the receiver operating characteristic curve [AUC] 0.91), IL-8 (48.7 vs. 103.3 pg/ml, AUC 0.85), IP-10 (176 vs. 566 pg/ml, AUC 0.83), MCP-1 (449 vs. 735 pg/ml, AUC 0.78), suPAR (3.5 vs. 5.2 ng/ml, AUC 0.78), MIG (100 vs. 152 pg/ml, AUC 0.75), and HGF (3.69 vs. 5.58 ng/ml, AUC 0.71) were significantly higher in patients with cirrhosis. In conclusion, several of the investigated markers showed promise for differentiating cirrhosis from no/mild fibrosis among patients with CHC genotype 1.     

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is a worldwide health problem that may evolve to cirrhosis and hepatocellular carcinoma. Incompletely understood immune system mechanisms have been associated with impaired viral clearance. The nonclassical class I human leukocyte antigen G (HLA-G) molecule may downregulate immune system cell functions exhibiting well-recognized tolerogenic properties. HCV genotype was analyzed in chronic HCV-infected patients. Because HLA-G expression may be induced by certain viruses, we evaluated the presence of HLA-G in the liver microenvironment obtained from 89 biopsies of patients harboring chronic HCV infection and stratified according to clinical and histopathological features. Overall, data indicated that HCV genotype 1 was predominant, especially subgenotype 1a, with a prevalence of 87%. HLA-G expression was observed in 45 (51%) liver specimens, and it was more frequent in milder stages of chronic hepatitis (67.4%) than in moderate (27.8%; p = 0.009) and severe (36.0%; p = 0.021) stages of the disease. Altogether, these results suggest that the expression of HLA-G in the context of HCV is a complex process modulated by many factors, which may contribute to an immunologic environment favoring viral persistence. However, because the milder forms predominantly expressed HLA-G, a protective role of this molecule may not be excluded.     

HCMV感染对人THP-1细胞HLA-G及其受体表达的影响

目的:研究人巨细胞病毒(HCMV)感染对人THP-1细胞人类白细胞抗原G(HLA-G)异构体及其受体表达的影响探讨HLA-G在HCMV逃逸宿主免疫应答中的作用。方法:HCMV Towne株感染THP-1细胞后,采用RT-PCR和Western blot检测HLA-G异构体mRNA和蛋白水平,流式细胞术检测THP-1细胞HLA-G及其表面受体ILT2、ILT4的表达,ELISA检测细胞培养上清中IL-10及可溶性HLA-G(sHLA-G)水平,同时检测细胞存活率。结果:HCMV感染后细胞未出现明显凋亡,细胞存活率高。HCMV感染THP-1细胞1 d后HLA-G1、-G3、-G4和-G5的mRNA表达明显上调,HLA-G1和HLA-G5的蛋白表达明显上调。THP-1细胞HLA-G、ILT2和ILT4的表达在感染1 d后明显上调。sHLA-G水平在感染1 d后显著升高,与对照组比较差异有统计学意义(P0.01)。THP-1细胞培养上清液IL-10水平在感染1 d后明显上调,与对照组比较,差异有统计学意义(P0.05)。结论:HCMV感染THP-1细胞能诱导HLA-G异构体的差异表达,以HLA-G1和HLA-G5为主,且上调其表面受体ILT2/ILT4的表达。同时,HCMV感染能诱导THP-1细胞分泌IL-10。该研究为进一步探讨HCMV逃避机体免疫应答的机制提供实验依据。     

HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease mainly mediated by the deposit of immune complexes and defects in T lymphocytes and antigen-presenting cells along with a high production of T-helper 2 cytokines. A tolerance-inducible function of nonclassical class Ib human leukocyte antigen (HLA)-G molecule in innate and adaptive cellular responses has been reported, suggesting a role in inflammatory diseases. A 14 bp sequence insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene has been associated to the stability of HLA-G messenger RNA. The insertion of the 14 bp sequence seems to be associated with lower levels of soluble HLA-G (sHLA-G). The aim of this study was to evaluate the possible association of the presence of the 14 bp sequence (+14 bp) with SLE. We have HLA-G genotyped 200 SLE patients and 451 healthy control subjects (HS; Italian) and analyzed the plasma levels of sHLA-G and interleukin-10 (IL-10) in a subset of SLE patients and healthy subjects (Italian and Danish). A significant increase of the +14 bp HLA-G allele was detected in the Italian SLE patients compared with HS [P = 0.003, OR 1.44 (95% CI 1.13-1.82)]. A significant increased frequency of HLA-G +14/+14 bp and a decreased frequency of HLA-G -14/-14 bp were observed in SLE patients. There median concentration of sHLA-G was significantly lower in the plasma of SLE patients compared with that in the plasma of healthy controls (P < 0.0001). Furthermore, the results confirmed higher concentrations of IL-10-positive plasma in SLE patients. These results support a potential role for HLA-G in the susceptibility of SLE.     

血清中IL-6和IL-10变化与慢性乙肝急性发作导致肝衰竭的关系

目的通过分析急性发作慢性乙型肝炎（慢性乙肝）患者体内IL-6、IL-12、γ干扰素和IL-10的变化,探讨急性发作及病情严重程度与细胞因子变化的关系。方法对154例急性发作及免疫耐受慢性乙肝患者采用ELISA法检测IL-6、IL-12、γ干扰素和IL-10的水平,同时检测肝功能、HBV DNA定量等。结果处于急性发作的患者年龄较大,HBV DNA定量较低,促炎症因子和抗炎症因子的水平均高于处于免疫耐受的患者;重型肝炎组IL-6的水平（179.80±134.96）pg/ml高于非重型肝炎组（108.80±113.23）pg/ml（P〈0.05）,而IL-10的水平（12.80±4.96）pg/ml低于非重型肝炎组（20.33±7.35）pg/ml（P〈0.05）。结论慢性乙肝急性发作可能与炎症因子的激活相关,IL-6有促进肝损伤作用,而IL-10可能在避免过强免疫损伤中起重要作用。     

Evidence of a T helper type 2 activation in human schistosomiasis

The lymphocyte proliferative response and cytokine production to S. mansoni antigen in vitro were evaluated in 22 schistosomiasis patients living in an area endemic for this disease. The majority of patients (86%) showed no lymphocyte proliferative response and none of them showed interferon-γ (IFN-γ) production, following in vitro stimulation with soluble adult worm antigen preparation (SWAP). In contrast, interleukin (IL)-5 (2038 ± 1757 pg/ml) and IL-10 (867 ± 762 pg/ml) were detected in peripheral blood mononuclear cell (PBMC) cultures stimulated with SWAP. Moreover, mRNA for IL-4 was detected in SWAP-stimulated PBMC from 4 of 6 patients evaluated. Restoration of lymphoproliferative response was achieved in 4 of 6 patients by adding anti-IL-10 monoclonal antibody (mAb) to PBMC cultures [mean stimulation index (SI) in the presence of antigen = 2.7 ± 2.9; SI in the presence of antigen plus anti-IL-10, 21 ± 16]. Restoration of IFN-γ production by addition of anti-IL-10 mAb was achieved in 4 of 12 patients evaluated (248, 350, 687 and 710 pg/ml). Moreover, the addition of IL-10 to PBMC cultures of 3 schistosomiasis patients and 2 cured subjects who had high lymphoproliferative responses to SWAP resulted in the suppression of these responses by 90%, and completely suppressed IFN-γ production in one of the subjects, whose PBMC produced IFN-γ after stimulation with SWAP. The presence of IL-4 mRNA, high levels of IL-5, and the absence of IFN-γ in PBMC culture supernatants from infected patients, supports the conclusion that patients living in an endemic area of schistosomiasis express a predominant T helper type 2 response. The high levels of IL-10 and the ability of neutralizing anti-IL-10 mAb to restore T cell responses indicate that this cytokine plays an important role in the modulation of T cell responses in schistosomiasis.     

Interferon-gamma +874 T/A and interleukin-10 -1082 A/G single nucleotide polymorphism in Egyptian children with tuberculosis

The aim was to investigate the association of interferon-gamma (IFN-γ) +874 T/A and interleukin-10 (IL-10)-1082 A/G single nucleotide polymorphisms with tuberculous infection and post-BCG lymphadenitis in Egyptian children. IFN-γ +874 T/A and IL-10 -1082 A/G polymorphism detection by amplification refractory mutation system technique was carried out for 110 patients with TB, 40 patients with post-BCG lymphadenitis and 118 healthy controls. IFN-γ +874 A allele was higher in TB and post-BCG patients than those in healthy controls (Pc=0.006 and 0.002, respectively). IFN-γ +874 genotype AA was significantly higher in patients with TB than that in control (Pc=0.015), in extrapulmonary than patients with pulmonary TB (PTB) (Pc=0.009), and young children with TB below 5 years (Pc=0.024). No statistically significant differences were observed between patients with TB and controls for the frequency of IL-10(-1082) alleles or genotypes (P>0.05); however, a statistically significant difference in the frequency of IL-10 (-1082) GG genotype was found between patients with pulmonary and extrapulmonary TB (Pc=0.003). Low producer IFN-γ +874 A/A genotype is associated with post-BCG lymphadenitis and TB disease especially in younger children below 5 years. IL-10-1082 G/G genotype did not exhibit significant association except for increased GG frequency in PTB. Both cytokine polymorphisms have no relation to tuberculin reaction in patients with TB.     

畅迪治疗小儿异位性皮炎疗效观察及其对血清因子水平的影响

目的 检测异位性皮炎患儿血清中IL-4、IFN-γ水平变化,探讨Thl与Th2的平衡与异位性皮炎之间的关系及畅迪对血清因子的影响.方法 采用ELISA法检测30例健康小儿和采用粉尘螨滴剂治疗前后的30例异位性皮炎患儿血清中IL-4,IFN-γ水平,并观察药物的临床疗效.结果 患儿治疗前血清中IL-4浓度(98.64±2...     

HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent pregnancy loss from Basrah province in Iraq

HLA-G is a nonclassical, class I major histocompatibility complex (MHC) gene that exhibits immunomodulatory properties and likely plays a role in the maintenance of successful pregnancy. In this study, we investigated the role of HLA-G polymorphisms on risk for recurrent pregnancy loss (RPL) and on circulating levels of soluble (s)HLA-G in Iraqi women. DNA and plasma were obtained from blood samples collected at 9-12 weeks gestation from 50 women with RPL and 50 healthy pregnant women in Basrah province, Iraq. As measured by ELISA, median sHLA-G levels were significantly lower in the RPL cases compared to healthy controls (21.4 vs. 38.8 U/ml, respectively; P=0.025), and decreased with increasing maternal age (P=0.0051). However, HLA-G allele and haplotype frequencies did not differ significantly between cases and controls (P values ≥0.12 for all tests). In contrast, homozygosity for the C allele (CC) at a tri-allelic promoter polymorphism, -725C/G/T, was associated with lower concentrations of sHLA-G compared to the CG or CT genotypes (median levels 21.1 vs. 40.1 vs. 42.6 U/ml, respectively; P=0.0089). These results demonstrate that HLA-G genotype influences circulating sHLA-G levels during pregnancy but is not significantly associated with risk of RPL.     

Association between HLA-G 14bp Gene Polymorphism and Serum sHLA-G Protein Concentrations in Preeclamptic Patients and Normal Pregnant Women

Background: Preeclampsia (PE) is a multisystem syndrome that is a primary source of fetal–maternal morbidity and mortality. Human leukocyte antigen-G (HLA-G) is a nonclassical Major histocompatibility complex (MHC) class-Ib molecule expressed on the extravillous trophoblast and seems to have immunomodulatory functions during pregnancy. The purpose of our study was to investigate whether HLA-G may be a vital marker in the modulation of the pregnancy.

Methods: In this case-control study, a number of 150 healthy pregnant women and 150 patients with PE had been genotyped for the 14 base-pair (bp) insertion/deletion polymorphism in exon 8 of the HLA-G gene, and the serum level of soluble HLA-G (sHLA-G) protein was measured using the enzyme-linked immunosorbent assay.

Results: Data showed that the PE syndrome was not related to the HLA-G 14 bp genotype. But, the serum level of sHLA-G in PE patients was significantly lower than that in healthy pregnant women in the third trimester (11.74 and 24.48 U/ml, respectively, p < 0.001). However, no significant association was observed between the HLA-G 14 bp genotype and serum sHLA-G level.

Conclusion: Our results demonstrate that measurement of sHLA-G protein level may be helpful as a primary diagnosis for the pathogenesis of PE. Overall, this study suggests that the association between HLA-G 14 bp polymorphism and serum sHLA-G level in different ethnic populations of PE should be taken into consideration.     

Detection of serum soluble HLA-G levels in patients with acute ischemic stroke: A pilot study

The aim of this study was to investigate the potential role of soluble Human Leukocyte Antigen-G (sHLA-G) molecules as biomarkers predicting outcome in acute ischemic stroke (AIS). Serum levels of total sHLA-G (sHLA-G1/HLA-G5) and its soluble isoforms sHLA-G1 and HLA-G5/G6 were measured by enzyme-linked immunosorbent assay (ELISA) in 92 AIS patients and healthy donors (HD). Incidence of hemorrhagic transformation (HT), size of final infarct volume (FIV) and clinical outcome at 3 months were recorded in AIS patients. Detectable serum levels of sHLA-G1/HLA-G5, HLA-G5/G6 and sHLA-G1 were present in a small proportion of AIS patients (26.1%, 17.4% and 16.3%, respectively) and HD (12.5%, 10.7% and 10.7%, respectively) and were more elevated in AIS patients without HT than in those with HT (p < 0.01; p < 0.05; p < 0.01, respectively). HT was less frequent (p < 0.01) in AIS patients with measurable serum concentrations of sHLA-G1/HLA-G5 and HLA-G5/G6. Serum levels of sHLA-G1/HLA-G5 and sHLA-G1 were inversely correlated to FIV (p < 0.02), whereas good outcome was more common (p < 0.01) in AIS patients with detectable serum concentrations of sHLA-G1/HLA-G5. Taken together, these findings suggest that total sHLA-G could exert a protective effect in a subset of AIS patients, irrespective of its soluble isoforms sHLA-G1 and HLA-G5/G6, and indicate that the prognostic value of serum levels of sHLA-G remains to be established.