Discovery and Evaluation of new Combined Immunodeficiency Disease Entities (DECIDE)

联合免疫缺陷(CID)描述了一种由细胞和体液免疫系统失效所定义的疾病。这种失败的程度不一，从严重联合免疫缺陷(SCID)患者几乎完全缺乏适应性免疫系统，即受影响的儿童--如果没有治疗--由于压倒性感染而在出生一年内死亡，到轻微的形式，主要是基于T细胞数量变化诊断出来的。深度CID(PCID)是指发病率和死亡率较高，但在第一年内不会导致死亡的疾病实体。虽然大多数SCID相关基因的遗传背景已经确定，并在世界范围内启动了新生儿筛查计划来筛查这些患者，但pCID的分子起源尚不清楚，由于这组疾病的异质性来源，常见的筛查试验经常失败。鉴于pCID的常染色体隐性遗传特征，pCID在近亲婚姻发生率较高的种族群体中更常见。在来自巴勒斯坦医院的医生和科学家的三方合作中，以色列哈大沙大学和德国慢性免疫缺陷中心决定寻求确定患有pCID的儿童，发现和评估其疾病的潜在分子原因，从而确定更好的治疗方案，包括造血干细胞移植(HSCT)。通过密切的联合努力，我们将详细描述这种疾病的个体临床、遗传和免疫学方面。PCID新的遗传病因的发现和功能评估不仅有利于受累家庭，而且将为整个免疫缺陷领域乃至新的视野扩大我们对基础免疫学的理解，为诊断和治疗这一严重疾病提供新的重要信息。通过共同的教育方案，Decision将提高对这一疾病群体的认识，在以色列和巴勒斯坦建立新的设施，用于人类免疫缺陷的诊断和研究，从而加强巴勒斯坦、以色列和德国医生和科学家之间的长期合作。

Combined immunodeficiency (CID) describes a condition defined by the failure of the cellular and humoral immune system. The degree of this failure varies from nearly complete absence of the adaptive immune system in severe combined immunodeficiency (SCID), whenaffected children - if untreated - die within the first year of life due to overwhelming infections, to mild forms diagnosed based on numerical alterations mainly of the T cells. Profound CID (pCID) refers to disease entities which are associated with a high morbidity andmortality but do not lead to death within the first year. While the genetic background of most SCID related genes has been identified and new born screening programs have been started world wide to screen for these patients, the molecular origin of pCID is less wellunderstood and common screening tests often fail due to the heterogeneous origin of this group of diseases. Given the frequently autosomal-recessive trait of inheritance pCID is more often found in ethnic groups with a higher prevalence of consanguineous marriages.In a trilateral cooperation between physicians and scientists from Palestinian hospitals, Hadassah University in Israel and the Centre for Chronic Immunodeficiency in Germany DECIDE seeks to identify children with pCID, discover and evaluate the underlying molecularcause of their disease and thereby determine better treatment Options including hematopoietic stem cell transplantation (HSCT). Through the close combined effort we will describe the individual clinical, genetic and immunological side of the disease in detail. The discoveryof new genetic causes of pCID and their functional evaluation will not only be advantageous for the affected family, but it will provide new important information on diagnosis and therapy of this severe sickness to the whole field of immunodeficiency and often the newinsights even expand our comprehension of basic immunology. Through common educational programs DECIDE will increase the awareness of this disease group, build new facilities in Israel andPalestine for the diagnosis and research of human immunodeficiency and thus strengthen the long-term collaboration between Palestinian, Israeli and German physicians and scientists.