Lymphoproliferative Disorders in Primary Immunodeficiencies

原发性免疫缺陷中的淋巴增殖性疾病

基本信息

批准号：
8206706
负责人：
John Michael Routes
金额：
$ 31.44万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-01 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8206706
关键词：
B-Cell Lymphomas B-Cell NonHodgkins Lymphoma Biopsy Bone Marrow Cancer Etiology Cellular Immunity Chronic Active Hepatitis Common Variable Immunodeficiency Cytokine Gene DNA Sequence Defect Development Etiology Family member Genes Genetic Polymorphism Grant Granulomatous HIV-1 Herpesviridae Household Human Human Genome Immune system Immunologic Deficiency Syndromes Immunosuppression Infection Inflammatory Interleukin-10 Interleukin-6 Interstitial Lung Diseases Link Liver Liver diseases Lung Lung diseases Lymph Node Tissue Lymphocyte Lymphoproliferative Disorders Malignant - descriptor Malignant Neoplasms Molecular Morbidity - disease rate Mutation Open Reading Frames Patients Phylogeny Prevalence Production Risk Role Source Staging Susceptibility Gene TNF gene Virus cohort congenital immunodeficiency cytokine high risk latent nuclear antigen liver biopsy lymph nodes mortality pathogen promoter

项目摘要

We demonstrated that patients with common variable immunodeficiency (CVID) and granulomatous and lymphocytic interstitial lung disease (GLILD) are at high risk for the development of B cell lymphomas and early mortality. We also found that a majority of patients with CVID and GLILD (CVID-GLILD) were infected with human herpes virus type 8 (HHV8). In Aim 1, we will determine the prevalence of HHV8 infection in patients with a larger cohort of patients with CVID and broad spectrum of primary immunodeficiencies. To identify the source of HHV8, we will determine the prevalence of HHV8 infection in family members and household contacts of infected and uninfected patients with CVID and determine the molecular phylogeny of HHV8 in infected cohorts by amplifying the highly polymorphic HHV8 K1 ORF by PCR and performing DNA sequencing of the K1 amplicon. In Aim 2, we will expand our observations on the role of HHV8 infection in lymphoproliferative disorders, lung and liver disease in patients with CVID by examining lung, liver or lymph node tissue biopsies for evidence of HHV8 infection. In Aim 3, we will determine if abnormalities in cellular immunity identify patients with CVID at risk for infection with HHV8 and determine if specific promoter polymorphisms in the IL- 6, TNF-α or IL-10 genes or mutations in the TACI gene predispose patients with CVID to infection with HHV8. Aim 1: Ascertain the molecular phylogeny of HHV8 in CVID patients infected with HHV8 and determine if HHV8 is an opportunistic pathogen in a larger cohort of patients with CVID and other primary immunodeficiencies. Aim 2: Ascertain the role of HHV8 infection in the etiology of lung disease, liver disease, lymphoproliferative disorders in patients with CVID. Aim 3: Determine if promoter polymorphisms of cytokine genes, dysregulated inflammatory cytokine production, and defects in cellular immunity or mutations in the TACI gene predispose patients with CVID to infection with HHV8.

我们证明患有常见变异型免疫缺陷（CVID）和肉芽肿性和淋巴细胞性间质性肺病 (GLILD) 的风险很高 B 细胞淋巴瘤的发展和早期死亡。我们还发现，大多数患者 CVID和GLILD（CVID-GLILD）均感染人类疱疹病毒8型（HHV8）。在目标 1，我们将确定更大队列患者中 HHV8 感染的患病率患有 CVID 和广谱原发性免疫缺陷的患者。识别来源 HHV8，我们将确定家庭成员和家庭中HHV8感染的流行情况感染和未感染 CVID 患者的接触者并确定分子系统发育通过 PCR 扩增高度多态性的 HHV8 K1 ORF 来检测受感染群体中的 HHV8 对 K1 扩增子进行 DNA 测序。在目标 2 中，我们将扩展我们的观察 HHV8 感染在患者淋巴增殖性疾病、肺病和肝病中的作用通过检查肺、肝或淋巴结组织活检以寻找 HHV8 证据来进行 CVID 感染。在目标 3 中，我们将确定细胞免疫异常是否可识别患有以下疾病的患者： CVID 有感染 HHV8 的风险，并确定 IL- 中是否存在特定启动子多态性 6、TNF-α或IL-10基因或TACI基因突变使CVID患者易患感染 HHV8。目标 1：确定感染 HHV8 和 HHV8 的 CVID 患者中 HHV8 的分子系统发育确定 HHV8 是否是较大 CVID 患者队列中的机会性病原体其他原发性免疫缺陷。目标 2：确定 HHV8 感染在肺部疾病、肝脏疾病、 CVID 患者的淋巴增殖性疾病。目标 3：确定细胞因子基因的启动子多态性是否会导致炎症失调细胞因子的产生、细胞免疫缺陷或 TACI 基因突变易诱发 CVID 患者感染 HHV8。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID).

使用联合化疗治疗常见变异型免疫缺陷（CVID）患者的肉芽肿性和淋巴细胞性间质性肺疾病（GLILD）。

DOI：
发表时间：
2013-01
期刊：
影响因子：
9.1
作者：
Chase, Nicole M;Verbsky, James W;Hintermeyer, Mary K;Waukau, Jill K;Tomita;Casper, James T;Singh, Sumit;Shahir, Kaushik S;Tisol, William B;Nugent, Melodee L;Rao, R Nagarjun;Mackinnon, A Craig;Goodman, Lawrence R;Simpson, Pippa M
通讯作者：
Simpson, Pippa M

Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases.

肉芽肿性和淋巴细胞性间质性肺病：常见变异性免疫缺陷的一系列肺部组织病理学病变——16例的组织学和免疫组织化学分析。