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，包括由于抗IFNg自身抗体引起的免疫缺陷和由于抗GM-CSF自身抗体引起的肺泡蛋白沉积症。 一些患者对优化的常规治疗难治或对标准方法严重不耐受。 我们将招募抗细胞因子自身抗体综合征患者，这些患者尽管接受了优化的常规治疗，但疾病仍进行性。 我们将对患者进行治疗并采集其血液，并评估受疾病影响的区域（无论如何适当），即抗IFNg-自身抗体相关深部感染的成像，抗IL-17-自身抗体相关念珠菌病的内窥镜检查，GM-CSF自身抗体相关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的抗体筛查方法评价血液中自身抗体水平的变化，使用临床实验室评价炎症标志物，使用流式细胞术评价免疫学参数，如CD 40配体表达和B淋巴细胞亚群。 我们还将通过流式细胞术和ELIspot对单采患者进行预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，以评估疗效证据。 本研究已编写并通过NIH IRB。 我们已获得Genetech的支持，Genetech将为研究提供药物以及PK和PD数据，并搜索人抗嵌合抗体（HACAs）。 我们尚未招募患者参加本研究，因为Genentech于本月（2013年8月）启动了该研究。

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 been written and passed through the NIH IRB. We have garnered support from Genetech who will provide drug for the study as well as PK and PD data, and search for human anti-chimeric antibodies (HACAs). We have not yet enrolled patients to this study as it has just been activated by Genentech this month (8/2013).