艾可清胶囊治疗人类免疫缺陷病毒感染者的疗效及与人类白细胞抗原基因型的相关性

目的探索艾滋病病毒感染者与人类白细胞抗原(HLA)不同基因型的关系,并评价艾可清胶囊治疗人类免疫缺陷病毒(HIV)感染者的效果。方法收集HIV感染35例,艾滋病(AIDS)患者51例,其中HIV感染者服用艾可清胶囊,AIDS患者服用抗病毒西药,采用聚合酶链式反应-序列特异性引物技术(PCR-SSP)检测所有患者的HLA-B基因型,并进行Karnovsky评分和T淋巴细胞亚群、血常规检测,并对艾可清胶囊疗效的危险因素进行分析。结果 AIDS患者Bw4Bw4基因型的CD4、CD8及Th/Ts治疗后与治疗前相比明显升高,Bw4Bw6基因型的CD4和Th/Ts治疗后与治疗前相比亦明显升高(P<0.01)。HIV感染者不同基因型T细胞治疗前后变化无统计学意义(P>0.05)。艾可清胶囊效佳组治疗后CD4、Karnovsky评分、体重、白细胞、淋巴细胞绝对值均较治疗前明显上升(P<0.05或P<0.01);年龄为影响艾可清胶囊疗效的主要因素。结论携带HLA-Bw4Bw4基因型患者免疫功能恢复快于其他基因型,说明人类自身遗传背景可以影响病情进展,并发现艾可清胶囊可能对40岁以下人群效果更佳。     

T cell recognition of HLA‐A2 restricted tumor antigens is impaired by the oncogene HER2

The HER2 oncogene is frequently over‐expressed in human cancers and a promising target for immune therapy. Previous studies have shown that over‐expression of mouse or rat HER2 leads to markedly reduced levels of major histocompatibility complex (MHC) class I and molecules of the antigen processing and presentation machinery (APM), thus resulting in a phenotype promoting tumor escape from the immune system. Our study focuses on analyzing the effect of HER2 on MHC class I antigen presentation and sensitivity to tumor‐antigen specific cytotoxic T lymphocytes (CTLs) in HLA‐A2.1⁺ melanoma cell lines. We demonstrate significant inverse correlations both between the expression of HER2 and total MHC class I surface expression as well as between HER2 and HLA‐A2. A significant reduction of HLA‐A2 levels was found when melanoma and carcinoma cell lines were transfected with a human HER2 gene. A signaling‐competent HER2 molecule was crucial for the observed HLA‐A2 down‐regulation, as transfectants expressing high levels of HER2 mutated in the tyrosine signaling domain did not show altered HLA‐A2 expression. Importantly, the human melanoma cell line EST049 demonstrated reduced HER2 and melanoma antigen‐specific recognition by CTLs upon HER2 transfection. In addition, high expression of HER2 prevented both IFN‐γ mediated HLA‐A2 up‐regulation and improved recognition by HLA‐A2‐restricted CTLs in treated cells. Moreover, key APM molecules were down‐regulated by HER2. These findings implicate that HER2 over‐expressing tumors may be more prone to escape from HLA‐A2 restricted CTLs suggesting that immunotherapy approaches inducing an integrated humoral, cellular and innate immune response would be most effective.     

Frequency distribution of HLA DQ2 and DQ8 in celiac patients and first-degree relatives in Recife, northeastern Brazil

AIMS:

The aim of this study was to evaluate the frequencies of the HLA genotypes DQ2 and DQ8 and the alleles A1*05, A1*0201, B1*0201 and B1*0302 in individuals with celiac disease in Recife, northeastern Brazil.

METHODS:

HLA DQ2 and DQ8 genotyping was performed for 73 individuals with celiac disease and 126 first-degree relatives with negative transglutaminase serology. The alleles DQA1*05, DQA1*0201, DQB1*02 and DQB1*0302 were identified by sequencing using specific primers and the EU-DQ kit from the Eurospital Laboratory, Trieste, Italy and double-checked by the All Set SPP kit (Dynal).

RESULTS:

Among the 73 cases, 50 (68.5%) had the genotype DQ2, 13 (17.8%) had DQ8, 5 (6.8%) had DQ2 and DQ8, and 5 did not have any of these genotypes. Among the 5 negative individuals, four had the B1*02 allele and one did not have any of the alleles studied. B1*02 was the most frequent allele in both groups (94% in the patients and 89% in the control relatives).

CONCLUSIONS:

In this study, celiac disease was associated with the genotypes DQ2 and DQ8. DQ2 predominated, but the distribution of the frequencies was different from what has been found in European populations and was closer to what has been found in the Americas. The high frequencies of the HLA genotypes DQ2 and DQ8 that were found in first-degree relatives would make it difficult to use these HLA genotypes for routine diagnosis of celiac disease in this group.     

Hematopoietic stem cell transplantation in children

Medical and nursing care of the hematopoietic stem cell transplantation (HSCT) recipient are complex because of the pathophysiology, HSCT process, pre-HSCT conditioning regimens, numerous medications and therapies, acute and chronic complications, adverse effects, resources involved, and environmental considerations. The HSCT process and therapies may affect any body system, requiring proficient and prioritized nursing care, possibly in an intensive care setting. Understanding the timing of potential adverse effects and complications based on engraftment will help provide competent, high-acuity care. Although autogenic and allogeneic HSCT are curative treatment options, there are numerous morbidity and/or mortality risks throughout the HSCT journey.     

Correlation of HLA B27 subtypes with clinical features of ankylosing spondylitis

Aim: The aim of the present study was to identify the B*27 subtypes associated with ankylosing spondylitis (AS) in our population and correlate them with clinical features of AS. Method: Whole blood samples were collected from 81 HLA‐B27 positive AS patients and 29 controls (asymptomatic healthy unrelated individuals) positive for HLA‐B27. Clinical details of the patients were recorded which included history of inflammatory back pain, sacroiliitis, spine involvement, enthesitis, peripheral arthritis and uveitis. HLA‐B27 subtypes were detected using commercially available techniques. Fisher’s exact test was used for statistical analysis. Results: The subtypes observed in AS patients were B*2705 (67.9%, 55/81), B*2704 (28.4%, 23/81), B*2707 (2/81) and B*2702 (1/81). Subtypes in the controls were B*2705 (62.07%, 18/29), B*2707 (27.59%, 8/29) and B*2704 (10.34%, 3/29). Uveitis was observed more in B*2704‐positive AS patients (34.78%, 8/23) compared to B*2705‐positive AS patients (16.36%, 9/55). However, the difference was not statistically significant (P = 0.130). No major differences were found between B*2705 and B*2704 for other clinical features. Conclusion: B*2705 was the main subtype observed in both patient and control groups. Frequency of B*2704 was more in AS patients compared to controls. Occurrence of AS‐associated uveitis was more often in B*2704‐positive AS patients compared to B*2705‐positive ones.     

HLA‐DRB1: genetic susceptibility and disability progression in a Spanish multiple sclerosis population

Background and objective: The association of HLA‐DRB1*15 with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical phenotype is still controversial. The objectives of this study are to investigate the influence of the HLA‐DRB1 alleles on the genetic susceptibility to MS and to study their impact on disability progression in a Spanish population. Methods: HLA‐DRB1 typing was performed by PCR‐SSP in 380 patients with sporadic MS and 1088 unrelated healthy controls. Allelic frequencies were compared between groups. We studied the correlation between the different alleles and the progression of MS. Results: The HLA‐DRB1*15 allele in patients with MS had a statistically significant higher frequency when compared with controls (18.9% in patients vs. 10.1% in controls, Odds ratio (OR) = 2.07, 95% CI = 1.64–2.60, P < 0.001). In the univariate analysis, the DRB1*01 and DRB1*04 alleles were associated with a worse prognosis when considering the time to reach an EDSS of 6, whereas the DRB1*03 was correlated with a better outcome. In the multivariate analysis, the alleles*01 and *04 were demonstrated to be independent factors to have a worse prognosis. Conclusions: HLA‐DRB1*15 is associated with MS when comparing patients with unrelated healthy controls in a Spanish population. The HLA‐DRB1*01 and HLA‐DRB1*04 alleles are related to a worse prognosis when considering the time taken to reach severe disability.     

Liver HLA‐G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection

Summary. As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)‐G is well described as a tolerogenic molecule, we evaluated HLA‐G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA‐G expression was assessed by immunohistochemistry. No HLA‐G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane‐bound HLA‐G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA‐G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA‐G expression presented a higher median HBV DNA viral load (10⁵ copies/mL) than those who did not express HLA‐G (10^3.7 copies/mL). These results indicate that HLA‐G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.