Clinical Studies Of Abnormal Host Defense

宿主防御异常的临床研究

• 批准号: 6984867
• 负责人: JOHN I GALLIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6984867
• 关键词: Chediak Higashi syndrome; calcium flux; cellular pathology; chemoprevention; chronic granulomatous disease; clinical trials; drug screening /evaluation; enzyme linked immunosorbent assay; human subject; human therapy evaluation; hydrogen peroxide; hyperglobulinemia; immunogenetics; inflammation; interferon alpha; itraconazole; longitudinal human study; mycosis; neutrophil; nucleic acid sequence; opportunistic infections; patient /disease registry; patient oriented research; phagocytic dysfunction

The purpose of this project is to study patients with abnormal host defense; to determine the cause of their abnormality; and to devise effective therapies for their underlying disorder and the life-threatening infections associated with their disease processes. The LHD has a long tradition of investigating patients with abnormalities of phagocytic cell function. These studies include early delineation of the clinical, functional, and in some cases, the molecular defects of patients with neutrophil specific granule deficiency, chronic granulomatous disease of childhood (CGD), leukocyte adhesion deficiency and the syndrome of hyperimmunoglobulin-E and recurrent infections and IRAK-4 deficiency. Cohorts of patients have been collected over the years which we continue to follow at NIH. Currently we follow over 150 patients with CGD, about 40 patients with the hyperimmunoglobulin-E recurrent infection syndrome, and 30 patients with other phagocyte dysfunction syndromes, including leukocyte adhesion deficiency, cyclic neutropenia, neutrophil specific granule deficiency and Chediak-Higashi syndrome and IRAK-4 deficiency. All these patients serve as a national resource for investigators desiring samples from patients and are available for clinical research protocols involving intramural or extramural scientists. We now have EB virus transformed B cells from most of our patients and we have been pleased to share these B cell lines with other intramural or extramural colleagues. We continue to monitor and expand these cohorts of patients who serve as models for long term studies of the immunological manipulation of the abnormal host defenses. This year we completed a long term study in 76 CGD patients enrolled in an uncontrolled, open label follow-up study to assess the long-term clinical safety and efficacy of interferon-?. We followed patients for up to 9 years (328 patient years). Serious infections were 0.3 per patient year (bacterial 0.18; fungal 0.12). Mild adverse events were common but tolerable in most patients (fever in 38% of patients. But some patients withdrew because of the adverse events (3) or patient preference (15), or for transfer to another trial (8). Children born to patients during the trial were healthy. There were no life-threatening interferon-? adverse events and no discernable effect on growth and development. The overall mortality was 6.6% over 9 years. Thus, interferon-? prophylaxis for CGD appears effective and well tolerated over a prolonged period of time.

该项目的目的是研究异常宿主防御的患者；确定其异常的原因；并为其潜在疾病的有效疗法以及与疾病过程相关的威胁生命的感染。 LHD具有研究吞噬细胞功能异常的患者的悠久传统。这些研究包括早期描述临床，功能和在某些情况下，中性粒细胞特异性颗粒缺乏症患者的分子缺陷，儿童慢性肉芽肿（CGD），白细胞粘附缺乏症以及超抗蛋白质 - E Hyproukocyte粘附缺乏症和综合征超抗蛋白 - E和复发性感染和伊拉克-4缺陷。多年来，已经收集了许多患者的同类，我们将继续在NIH遵循。 Currently we follow over 150 patients with CGD, about 40 patients with the hyperimmunoglobulin-E recurrent infection syndrome, and 30 patients with other phagocyte dysfunction syndromes, including leukocyte adhesion deficiency, cyclic neutropenia, neutrophil specific granule deficiency and Chediak-Higashi syndrome and IRAK-4 deficiency.所有这些患者都是希望来自患者样本的研究人员的国家资源，可用于涉及壁内或壁外科学家的临床研究方案。现在，我们拥有EB病毒从大多数患者中转化的B细胞，我们很高兴与其他壁内或壁外同事共享这些B细胞系。我们继续监视和扩展这些同类的患者，这些患者是对异常宿主防御的免疫操纵的长期研究模型的模型。 今年，我们完成了一项长期研究，对76名CGD患者进行了一项不受控制的开放标签随访研究，以评估干扰素的长期临床安全性和功效。我们跟踪患者长达9年（328例患者年）。严重感染是每年0.3（细菌0.18；真菌0.12）。轻度不良事件是常见但在大多数患者中忍受的（38％的患者发烧。但是有些患者因不良事件（3）或患者偏爱（15）或转移到另一项试验（8）而撤离。在试验期间出生的患者是健康的。没有生命的生命 - 没有不利的事件，并且对成长和发育不利。 CGD在长时间内看起来有效且耐受性良好。