HIV/AIDS的遗传背景及全基因组关联研究

宿主遗传背景是人类免疫缺陷病毒(HIV)感染机体后个体间表型差异的主要影响因素之一.它不仅影响HIV易感性,而且影响获得性免疫缺陷综合征(AIDS)进程.全基因组关联研究(GWAS)是一种在全基因组范围内检测与疾病相关基因的技术方法.目前,共有22项与HIV/AIDS相关的GWAS,发现了多个与HIV感染及AIDS进程相关的易感基因和位点.这些结果对研究宿主遗传背景在HIV感染中的作用、AIDS进程的预测及疫苗的研发都有重要意义.本文将对HIV/AIDS的遗传背景及其相关的GWAS作一综述.     

艾滋病相关腹部淋巴瘤多层螺旋CT增强特征及临床病理研究

目的:探讨艾滋病(Acquired immunodeficiency syndrome,AIDS)相关腹部淋巴瘤多层螺旋CT(Multisliecs helieal CT,MSCT)增强表现及临床病理特征。方法:回顾性分析2015年2月至2019年2月间我院收治的44例经病理检查确诊为AIDS相关腹部淋巴瘤患者的临床资料。对比AIDS病相关腹部淋巴瘤MSCT增强的表现特征及临床病理检查结果。结果:44例AIDS相关腹部淋巴瘤患者病理结果显示非霍奇金淋巴瘤42例(95.45%),霍奇金淋巴瘤2例(4.55%);按照解剖部位划分,病灶在腹主动脉周围(72.73.%)、肠系膜淋巴结(54.55%)、肠系膜根部(50.00%)、腹腔干周围(50.00%)、肝十二指肠韧带(50.00%)分布最为多见。MSCT表现为淋巴结肿大明显,部分呈肿块状,病灶中央可见低密度坏死区,邻近组织受压,未见明显侵犯。结论:AIDS病相关腹部淋巴瘤的MSCT增强表现具有一定特征性,在临床诊断与治疗中具有重要参考价值。     

HIV感染及AIDS的神经电生理异常

1981年美国首次报道获得性免疫缺陷综合征(艾滋病，AIDS)，此后全球患者逐年迅速上升。AIDS中有30％～80％神经系统受损，10％～27％神经系统症状为首发症状。人类免疫缺陷病毒(HIV)在基因、形态及分类学方面均与引起羊的慢性变性性神经病Visna病毒有关。HIV-1在血清感染后很快进入大脑，当免疫功能尚可抑制病毒的复制及扩散时，病毒可长期保留而无症状。     

050 T细胞免疫缺陷症的治疗

T细胞免疫缺陷症包括遗传性免疫缺陷和获得性免疫缺陷(见于AIDS患者和强烈化疗和／或放疗后引起T细胞的缺失)。遗传性免疫缺陷症的治疗方法有造血干细胞移植，胸腺移植，T细胞或造血干细胞的遗传修饰等。化疗和／或放疗后引起T细胞缺失的治疗原则是防止感染和提高免疫力。采用效应T细胞的过继性转移等。而对于AIDS患者的治疗主要是抑制HIV的复制。     

AIDS相关的淋巴结病的染色体异常

获得性免疫缺陷综合征(AIDS)是近年才出现的在同性恋、静脉给药者和受血者等人群中流行的一组疾病。其特征包括卡氏肺囊虫病、巨细胞病毒和其它机会感染、自身免疫现象、全身性淋巴结病、淋巴瘤和卡波齐氏肉瘤(KS)等。倘缺乏KS和机会感染证据,但具有上述其它特征者则称为AIDS相关综合征(ARC)。AIDS相关的淋巴结病属于淋巴瘤前期增生性疾病之一。目前关于其细胞遗传学资料尚不多见。因而,作者研究了该类患者的染色体改变,同时还测定了     

获得性免疫缺陷综合征合并肺部感染1例报告

艾滋病,即人类免疫缺陷病毒(HIV)感染引起获得性免疫缺陷综合征(AIDS),目前尚无有效治疗方法,晚期患者的免疫力低下且极易并发各种感染,对人类健康造成严重威胁.本所在临床收治了1例艾滋病合并肺部感染患者,现总结报告如下.     

T细胞免疫缺陷症的治疗

T细胞免疫缺陷症包括遗传性免疫缺陷和获得性免疫缺陷 (见于AIDS患者和强烈化疗和 /或放疗后引起T细胞的缺失 )。遗传性免疫缺陷症的治疗方法有造血干细胞移植 ,胸腺移植 ,T细胞或造血干细胞的遗传修饰等。化疗和 /或放疗后引起T细胞缺失的治疗原则是防止感染和提高免疫力 ,采用效应T细胞的过继性转移等。而对于AIDS患者的治疗主要是抑制HIV的复制。     

艾滋病患者心理状态分析及对策

<正>山西省艾滋病定点收治单位先后收治人免疫缺陷病毒(HIV)感染者/获得性免疫缺陷综合征(AIDS)患者55例,针对他们存在的心理问题及其特点进行干预和治疗效果明显,现报告如下。1HIV感染者/AIDS患者负性心理分析1.1疾病本身:一旦感染HIV,感染者就会产生比患任何疾病都严重、复杂的心理障碍,这种负性情绪一方面来自HIV/     

T细胞免疫缺陷症的治疗

T细胞免疫缺陷症包括遗传性免疫缺陷和获得性免疫缺陷（见于AIDS患者和强烈化疗和/或放疗后引起T细胞的缺失），遗传性免疫缺陷症的治疗方法有造血干细胞移植，胸腺移植，T细胞或造血干细胞的遗传修饰等，化疗和/或放疗后引起T细胞缺失的治疗原则是防止感染和提高免疫力，采用效应T细胞的过继性转移等，而对于AIDS患者的治疗主要是抑制HIV的复制。     

淋巴瘤患者HBV感染标志物及其DNA定量的实验室调查与分析

目的 探讨霍奇金淋巴瘤、非霍奇金淋巴瘤、弥漫性大B细胞淋巴瘤和T淋巴母细胞淋巴瘤患者HBV感染标志物和HBV DNA的表达情况.方法 选取近5年淋巴瘤科1779例住院病人,其中霍奇金淋巴瘤(Hodgkin's lymphoma,HL) 160例,非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL) 1590例,弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL) 16例,T淋巴母细胞淋巴瘤(T cell lymphoblasts lymphoma,T-LBL) 13例.健康查体者作为正常对照组(normal control group,NCG),共12890名,男性8450名,女性4440名.采用电化学发光法测定乙型肝炎病毒抗原和抗体;采用TaqMan实时荧光定量PCR方法测定乙型肝炎病毒DNA.结果 霍奇金淋巴瘤、非霍奇金淋巴瘤、弥漫性大B细胞淋巴瘤和T淋巴母细胞淋巴瘤的HBsAg、HBeAg的阳性率高于显著高于正常对照组;霍奇金淋巴瘤和非霍奇金淋巴瘤的HBcAb阳性率显著高于正常对照组;霍奇金淋巴瘤、非霍奇金淋巴瘤和弥漫性大B细胞淋巴瘤的HBsAb阳性率低于正常对照组;说明HBV携带者对HBV的免疫力较低,发生恶性淋巴瘤的风险较大.乙型肝炎病毒具有嗜淋巴细胞和嗜肝细胞的特性,淋巴瘤患者HBsAg携带率是正常对照组的4.1 ～10.9倍;霍奇金淋巴瘤和非霍奇金淋巴瘤患者HBV DNA的阳性率是正常对照组的2.2 ～8.3倍.结论 HBV感染与淋巴瘤的发生具有很强的相关性,患者血清的HBV抗原、抗体和DNA水平可能是淋巴瘤患者致病和HBV再激活的重要因素.对于用化疗药物或免疫抑制剂治疗的淋巴瘤患者,应定期对其肝功能和乙肝标志物进行检测.若出现肝功异常或HBV再激活等情况,应立即评估患者病情,及时调整治疗方案.     

Prognosis of AIDS-related systemic non-Hodgkin lymphoma treated with chemotherapy and highly active antiretroviral therapy depends exclusively on tumor-related factors

OBJECTIVES: To assess complete remission (CR) and survival in patients with systemic AIDS-related non-Hodgkin lymphoma (ARL) receiving highly active antiretroviral therapy (HAART). METHODS: We analyzed the Grupo de Estudio del SIDA register of systemic ARL, which started in Jan 1994, to collect cases diagnosed at 15 institutions prospectively and with active follow-up every 6 months. The date of censorship for this study was March 2005. RESULTS: During the study period, 210 consecutive patients were diagnosed with ARL, with a median age 39 of years, 75.7% of whom were male, and with a median baseline CD4 count of 160 cells/microL. Histologic subtypes were diffuse large B-cell lymphoma (DLCL; n = 153 [72.9%]), Burkitt and atypical Burkitt/Burkitt-like lymphoma (BL; n = 40 [19.0%]), T-cell lymphoma (TC; n = 8 [3.8%]), and miscellaneous (n = 9 [4.3%]). Chemotherapy with or without other modalities was administered to 186 (88.6%) patients. In an intent-to-treat analysis of 184 patients who received at least 1 chemotherapy course with adequate follow-up to assess their response, 119 (64.7%) achieved CR, and the median length of survival (Kaplan-Meier analysis) was 52 months (95% confidence interval [CI]: 23 to 82 months). Factors independently associated with CR were histologic subtype and International Prognostic Index (IPI) score. Factors independently associated with improved overall length of survival (OS) were CR, low IPI score, and histologic subtype. The single factor independently associated with disease-free survival was Ann Arbor stage. CONCLUSIONS: In patients with ARL treated with HAART, CR was associated exclusively with tumor-related factors. The CR rate was poorer in patients with BL and TC subtypes and was inversely correlated with IPI score. OS was independently associated with CR, IPI score, and the histologic subtype.     

AIDS-related non-Hodgkin lymphoma: still a problem in the era of HAART

Despite advances in HAART, patients with HIV infection remain at significantly increased risk for intermediate- and high-grade B-cell non-Hodgkin lymphoma. The reasons for this persistent risk and the clinical and molecular correlates that predict outcomes and treatment responsiveness are areas of active investigation. Here we review the epidemiologic and pathobiologic features of AIDS-related lymphoma along with clinical evaluation and treatment options in patients with this disease.     

Clinical Characteristics of Gastrointestinal Lymphomas Associated with AIDS (GI-ARL) and the Impact of HAART

Abstract

Purpose: The gastrointestinal (GI) tract is the most common site of extranodal disease in patients with systemic non-Hodgkin’s lymphoma (NHL). Patients with systemic NHL and GI involvement associated with AIDS (GI-ARL) have a significantly worse prognosis than those without AIDS. We studied whether the introduction of HAART is associated with improved survival in patients with GI-ARL. Patients and Method: 36 patients with GI-ARL were identified from the tumor registries of a large municipal hospital in New York City and a tertiary care facility in western New York State. Of these, 28 patients did not receive HAART and 8 were treated with HAART. The primary endpoint was survival, which was defined as time from date of diagnosis of NHL until death from any cause. Results: Patients were analyzed based on whether or not they were treated with HAART. Kaplan-Meier analysis showed significantly better survival in patients with GI-ARL who were concurrently treated with HAART (p = .014). Median survival was 5 months for the no-HAART group and 30 months for the HAART group. Conclusion: In patients with GI-ARL who were treated with chemotherapy, concurrent therapy with HAART therapy was associated with improved survival.     

Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months.     

Expression of Epstein-Barr virus replicative proteins in AIDS-related non-Hodgkin's lymphoma cells.

Epstein-Barr virus (EBV) infection in lymphoproliferative lesions has been assumed to be strictly latent. In order to investigate the possible occurrence of EBV replication in AIDS-related lymphoma (ARL) cells, we studied 13 cases by immunohistology using monoclonal antibodies to the EBV-encoded switch-protein BZLF1, early antigens (EAs), late replicative proteins [virus capsid antigens (VCAs) and membrane antigens (MAs)], and to the latent proteins EB nuclear antigen 2 (EBNA 2) and latent membrane protein (LMP). EBV genomes were detected by in situ hybridization. EBV genomes and/or gene products were demonstrated in ten cases, including all immunoblast-rich lymphomas, two Burkitts lymphomas, and a T-cell anaplastic large-cell lymphoma. The BZLF1 protein, which disrupts latency in B cells, was identified in six (60 per cent), and EAs in four (40 per cent) of the EBV-positive ARL. Only one lymphoma (10 per cent) expressed VCAs and MAs. EBNA 2 and LMP were detected in three (30 per cent) and eight (80 per cent) of EBV-positive cases, respectively. EBV DNA was detected in lymphoma cells in 7 of 12 (58 per cent) cases. The most important finding of this study was frequent spontaneous activation of latent EBV in ARL. Production of complete virus, however, was either aborted, or tumour cells expressing late productive cycle proteins (VCA, MA) were rapidly cleared from tissues. It is suggested that host factors that normally inhibit replication of EBV are deficient in AIDS patients.     

Differences in lymphoma patients between chimeric antigen receptor T-cell therapy trials and the general population

Chimeric antigen receptor (CAR)-T cell therapies appear to be promising treatments for non-Hodgkin’s and B-cell lymphoma. However, several CAR-T therapies approved by the US Food and Drug Administration have only been tested for efficacy in relatively few single-arm clinical trials with small sample sizes. We sought to examine the differences between patients in these trials and the general population of patients with non-Hodgkin’s and B-cell lymphoma. Five hundred and twenty-two patients from 15 CAR-T trials found in a systematic review and 417,492 patients from the Surveillance, Epidemiology, and End Results (SEER) Program database were compared. CAR-T study participants appeared to be younger (46.7% under 70 years old vs. 42.2%), more male (68.0% vs. 55.7%), and followed for a shorter period of time compared to patients in the SEER population (mean [M] 45.6 months, 95% confidence interval [CI] 17.7 to 63.3 months follow-up vs. M 57.1 months, 95% CI 57.0 to 57.3 months survival). CAR-T study participants may differ significantly from the general population of patients with non-Hodgkin’s and B-cell lymphoma. Effectiveness of CAR-T therapies in the general population of lymphoma patients may differ from effectiveness demonstrated in trials. Newly created CAR-T patient registries are essential to establishing population-level effectiveness of the therapies.

     

Assessment of Epstein-Barr virus association with pediatric non-hodgkin lymphoma in immunocompetent and in immunocompromised patients in Argentina

CONTEXT: Epstein-Barr virus (EBV) has been classically associated with 3 malignancies, Burkitt lymphoma, B-cell lymphoproliferative syndromes, and nasopharyngeal carcinoma, and more recently with Hodgkin disease, T-cell lymphomas, and gastric and breast carcinomas, as well as with leiomyosarcoma and leiomyoma associated with immunosuppression. OBJECTIVE: To compare EBV expression in Argentine tumor samples with those reported elsewhere, we analyzed EBV expression in an Argentine pediatric population with non-Hodgkin lymphoma and correlated these results with clinical course and outcome. METHODS: We studied EBV presence by latent membrane protein-1 protein labeling by immunohistochemistry, by in situ hybridization, and by polymerase chain reaction for Epstein-Barr-encoded RNAs (EBERs) in formalin-fixed and paraffin-embedded non-Hodgkin lymphoma tissue samples (collected retrospectively) from 32 pediatric patients at Ricardo Gutiérrez Children's Hospital from 1993 to 2000. RESULTS: Eight out of the 32 (25%) non-Hodgkin lymphoma cases showed latent membrane protein-1 and EBERs by in situ hybridization positive staining in tumor cells. Among EBERs and latent membrane protein-1-positive cases, there were 5 immunocompromised patients, with either human immunodeficiency virus infection or primary immunodeficiency. The EBERs in situ hybridization results were confirmed by EBERs polymerase chain reaction in good-quality DNA from 11 samples, with 3 proving positive and 8 negative. CONCLUSIONS: The association of EBV with non-Hodgkin lymphoma in the Argentine pediatric population was low (25%), and this figure rose to 100% when only the immunocompromised patients subgroup was considered, confirming that the virus is probably a cofactor in the lymphomagenesis of some but not all pediatric non-Hodgkin lymphoma. So far, no differences in clinical outcome are discernible between EBV-positive and EBV-negative non-Hodgkin lymphoma patients.     

Multicentric Castleman's disease in HIV infection: a systematic review of the literature

The objective of this study is to systematically review the epidemiology and the clinical and virologic aspects of multicentric Castleman's disease in HIV-positive patients and to evaluate treatment strategies and outcome, especially in relation to HAART administration. The authors have conducted a systematic review of the English literature for all cases of newly diagnosed multicentric Castleman's disease in HIV-positive patients. The 25 studies which met the selection criteria included 84 HIV-positive patients with multicentric Castleman's disease (20 pre-HAART and 64 post-HAART era). Of them, the majority (90%) were men with 33 months median time from detection of HIV-positivity to multicentric Castleman's disease diagnosis in the HAART era. Fever and lymphadenopathy were the most common presenting symptoms and cytopenias, hypoalbuminemia, polyclonal hypergammaglobulinemia and raised C-reactive protein the most frequently revealed laboratory findings. Kaposi's sarcoma was present in 72% of the patients and respiratory system involvement in 34%. Although the majority of cases reported were positive for human herpesvirus-8, none of the reviewed patients was found to suffer from polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Of the 48 patients on HAART, 64% were already on HAART at multicentric Castleman's disease diagnosis, having a better immunologic profile and a lower incidence of Kaposi's sarcoma than the 35% of patients who initiated HAART after multicentric Castleman's disease diagnosis. Nevertheless, the two groups did not have significantly different mortality rates (30 vs. 38%). At multicentric Castleman's disease diagnosis, a wide range of CD4 counts was recorded, suggesting that disease presentation could occur at any CD4 count. With regard to treatment, the study confirmed the high rates of response with rituximab (anti-CD20 monoclonal). Monochemotherapy seems to give short-lived responses, which require maintenance to be sustained. Polychemotherapy with CHOP has given long-term remission in a subset of patients. Other regimens used in the treatment of HIV-related multicentric Castleman's disease were antiviral agents, immunomodulatory agents, and thalidomide. The fatality rate among HIV-related multicentric Castleman's disease cases reviewed was 44%, significantly lower than that of HIV-negative individuals (65%), while median survival of the latter was 29 months longer than that of HIV-infected individuals. The fatality rate among pre-HAART patients was 75 vs. 29% among HAART patients. Infection, multiorgan failure, Kaposi's sarcoma, non-Hodgkin lymphoma and progressive multicentric Castleman's disease were the most often reported causes of death. In conclusion, multicentric Castleman's disease is a lymphoproliferative disorder with an increasing prevalence in HIV-infected individuals. Even though life expectancy in multicentric Castleman's disease seems to have significantly improved in the HAART era, it remains a disease with a poor prognosis and an increased incidence of non-Hodgkin lymphoma in the HIV-context.     

HIV-associated anal cancer: has highly active antiretroviral therapy reduced the incidence or improved the outcome?

BACKGROUND: Highly active antiretroviral therapy (HAART) has reduced the incidence and improved the survival of patients with Kaposi sarcoma and AIDS-related non-Hodgkin lymphoma. We wished to evaluate its effects on incidence and survival in HIV-associated anal cancer. METHODS: We measured the incidence and survival of patients with invasive anal cancer from our prospective cohort of 8640 HIV-seropositive individuals. RESULTS: In our cohort of 8640 HIV-seropositive individuals, the incidence of invasive anal cancer (diagnosed in 26 patients) is 60 per 100,000 patient-years. This is 120 times higher than in the age- and gender-matched general population. The incidence of invasive anal cancer in the HIV cohort was 35 (95% confidence interval CI: 15-72) per 100,000 patient-years of follow-up in the pre-HAARTera (1984-1995) and 92 (95% CI: 52-149) per 100,000 patient-years of follow-up in the post-HAARTera (1996-2003) (P > 0.05). These figures are significantly higher than those for the general population (P < 0.001 for both) and give a relative risk of 67 and 176 in the pre- and post-HAART eras, respectively, compared with the general population. The 5-year overall survival is 47% (95% CI: 24%-70%), and the 5-year disease-free survival is 66% (95% CI: 45%-87%). There is no difference in overall survival between the pre- and post-HAART eras (log rank P = 0.19). CONCLUSIONS: Unlike other HIV-associated cancers, there has been no significant change in the incidence, clinical features, or overall survival since the introduction of HAART.