Rituximab for Anticytokine Autoantibody-Associated Syndromes

抗细胞因子自身抗体已被证明是某些严重疾病的重要介质，包括抗IFNG自身抗体引起的免疫抑制和抗GM-CSF自身抗体引起的肺泡蛋白沉着症。一些患者对优化的传统疗法难以接受，或者对标准疗法有严重的不耐受。 我们将招募患有抗细胞因子自身抗体综合征的患者，这些患者尽管进行了优化的常规治疗，但仍有进展性疾病。我们将治疗患者，采集他们的血液，并适当地评估疾病影响区域，即针对抗IFNG自身抗体相关的深层感染的成像，针对抗IL-17自身抗体相关的念珠菌病的内窥镜检查，对于GM-CSF自身抗体相关的肺泡蛋白沉积症的支气管镜检查或CT成像。我们将使用基于Luminex的抗体筛选方法评估血液中自身抗体水平的变化，使用临床实验室评估炎症标志物，并使用流式细胞仪评估免疫学参数，如CD40配体表达和B淋巴细胞亚群。我们还将通过流式细胞仪和ELISPOT预先研究和鉴定抗原特异性B细胞(识别特定细胞因子)。我们还将在研究前和研究后进行生活质量调查，并对疾病活动进行临床评分，以评估疗效的证据。 这项研究得到了Genetech的支持，他们提供药物以及PK和PD数据，并搜索人类抗嵌合抗体(Hacas)。到目前为止，我们已经招募了2名患者参加这项研究。

Anti-cytokine autoantibodies have been shown to be an important mediator of certain serious diseases including immunodeificncy due to anti-IFNg autoantibodies and pulmonary alveolar proteinosis due to anti-GM-CSF autoantibodies. Some patients are refractory to optimized conventional therapy or have serious intolerance to standard approaches. We will be enrolling patients with anticytokine autoantibody syndromes who have have progressive disease despite optimized conventional treatment. We will treat patients and collect their blood and evaluate disease-affected regions however appropriate, i.e. imaging for anti-IFNg-autonantibody associated deep-seated infections, endoscopy for anti-IL-17-autoantibody-associated candidiasis, bronchoscopy or CT imaging for GM-CSF autoantibody associated pulmonary alveolar proteinosis. We will evaluate blood for changes in autoantibody levels using out luminex-based method for antibody screening, inflammatory markers using the clinical lab, and immunological parameters such as CD40 Ligand expression and B lymphocyte subsets using flow cytometry. We will also apherese patients prestudy and identify antigen-specific B cells (that recognize specific cytokines) by flow cytometry and ELIspot. We will also perform a quality of life survey pre and post study and clinically score disease activity to evaluate for evidence of efficacy. This study has support from Genetech who are providing drug as well as PK and PD data, and search for human anti-chimeric antibodies (HACAs). We have enrolled 2 patients to this study so far.