Straus S E, Sneller M, Lenardo M J, Puck J M, Strober W
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1888, USA.
Ann Intern Med. 1999 Apr 6;130(7):591-601. doi: 10.7326/0003-4819-130-7-199904060-00020.
The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that regulate lymphocyte homeostasis and underlie the development of autoimmunity. This syndrome arises early in childhood in persons who inherit mutations in genes that mediate apoptosis, or programmed cell death. The timely deletion of lymphocytes is a way to prevent their accumulation and the persistence of cells that can react against the body's own antigens. In ALPS, defective lymphocyte apoptosis permits chronic, nonmalignant adenopathy and splenomegaly; the survival of normally uncommon "double-negative" CD3+ CD4- CD8- T cells; and the development of autoimmune disease. Most cases of ALPS involve heterozygous mutations in the lymphocyte surface protein Fas that impair a major apoptotic pathway. Detailed immunologic investigations of the cellular and cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenotype; this provides a rational explanation for the humoral autoimmunity typical of patients with ALPS. Prospective evaluations of 26 patients and their families show an ever-expanding spectrum of ALPS and its major complications: hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and neutropenia. Defective apoptosis may also contribute to a heightened risk for lymphoma.
自身免疫性淋巴细胞增生综合征（ALPS）为调节淋巴细胞稳态及自身免疫性疾病发生机制提供了新的见解。该综合征在儿童早期发生于那些继承了介导凋亡（即程序性细胞死亡）基因突变的个体。淋巴细胞的及时清除是防止其积累以及防止能够对机体自身抗原产生反应的细胞持续存在的一种方式。在ALPS中，有缺陷的淋巴细胞凋亡导致慢性非恶性淋巴结病和脾肿大；正常情况下罕见的“双阴性”CD3 + CD4 - CD8 - T细胞存活；以及自身免疫性疾病的发生。大多数ALPS病例涉及淋巴细胞表面蛋白Fas的杂合突变，这些突变损害了一条主要的凋亡途径。对ALPS患者细胞和细胞因子谱的详细免疫学研究显示，其显著倾向于T辅助2型表型；这为ALPS患者典型的体液自身免疫提供了合理的解释。对26例患者及其家属的前瞻性评估显示，ALPS及其主要并发症（脾功能亢进、自身免疫性溶血性贫血、血小板减少症和中性粒细胞减少症）范围不断扩大。凋亡缺陷也可能导致淋巴瘤风险增加。
