Musabak Ugur, Erdoğan Tuba, Ceylaner Serdar, Özbek Emre, Suna Nuretdin, Özdemir Binnaz Handan
Department of Immunology and Allergy, Baskent University School of Medicine, Ankara 06490, Ankara, Turkey.
Department of Medical Genetics, Lokman Hekim University, Ankara 06000, Turkey.
World J Clin Cases. 2023 Sep 16;11(26):6176-6182. doi: 10.12998/wjcc.v11.i26.6176.
Cytotoxic T Lymphocyte Antigen-4 (CTLA4) deficiency is a genetic defect that causes a common variable immunodeficiency (CVID) clinical phenotype. Several studies have reported an association between CTLA mutations or variants and various autoimmune diseases. Targeted therapy models, which have become increasingly popular in recent years, have been successful in treating CTLA4 deficiency. In this article, we discuss the clinical outcomes of abatacept treatment in a patient with CTLA4 and lipopolysaccharide-responsive beige-like anchor (LRBA) variants that was previously diagnosed with CVID.
A 25-year-old female patient, who was visibly cachectic, visited our clinic over the course of five years, complaining of diarrhea. The patient was diagnosed with ulcerative colitis in the centers she had visited previously, and various treatments were administered; however, clinical improvement could not be achieved. Severe hypokalemia was detected during an examination. Her serum immunoglobulin levels, CD19 B-cell percentage, and CD4/CD8 ratio were low. An endoscopic examination revealed erosive gastritis, nodular duodenitis, and pancolitis. Histopathological findings supported the presence of immune mediated enteropathy. When the patient was examined carefully, she was diagnosed with CVID, and intravenous immunoglobulin treatment was initiated. Peroral and rectal therapeutic drugs including steroid therapy episodes were administered to treat the immune mediated enteropathy. Strict follow-ups and treatment were performed due to the hypokalemia. After conducting genetic analyses, the CTLA4 and LRBA variants were identified and abatacept treatment was initiated. With targeted therapy, the patient's clinical and laboratory findings rapidly regressed, and there was an increase in weight.
The heterozygous CTLA4 variant identified in the patient has been previously shown to be associated with various autoimmune diseases. The successful clinical outcome of abatacept treatment in this patient supports the idea that this variant plays a role in the immunopathogenesis of the disease. In the presence of severe disease, abatacept therapy should be considered until further testing can be conducted.
细胞毒性T淋巴细胞抗原4（CTLA4）缺陷是一种导致常见变异型免疫缺陷（CVID）临床表型的基因缺陷。多项研究报道了CTLA突变或变异与各种自身免疫性疾病之间的关联。近年来越来越流行的靶向治疗模式已成功用于治疗CTLA4缺陷。在本文中，我们讨论了阿巴西普治疗一名先前被诊断为CVID且存在CTLA4和脂多糖反应性米色样锚定蛋白（LRBA）变异患者的临床结果。
一名25岁明显消瘦的女性患者在五年内多次就诊于我们的诊所，主诉腹泻。该患者在之前就诊的中心被诊断为溃疡性结肠炎，并接受了各种治疗，但未实现临床改善。检查期间检测到严重低钾血症。她的血清免疫球蛋白水平、CD19 B细胞百分比和CD4/CD8比值较低。内镜检查显示糜烂性胃炎、结节性十二指肠炎和全结肠炎。组织病理学结果支持免疫介导的肠病的存在。对该患者进行仔细检查后，诊断为CVID，并开始静脉注射免疫球蛋白治疗。给予包括类固醇治疗阶段在内的口服和直肠治疗药物以治疗免疫介导的肠病。由于低钾血症进行了严格的随访和治疗。进行基因分析后，鉴定出CTLA4和LRBA变异，并开始阿巴西普治疗。通过靶向治疗，患者的临床和实验室检查结果迅速好转，体重增加。
在该患者中鉴定出的杂合CTLA4变异先前已显示与各种自身免疫性疾病相关。该患者阿巴西普治疗的成功临床结果支持了这种变异在疾病免疫发病机制中起作用的观点。在存在严重疾病的情况下，在进行进一步检测之前应考虑阿巴西普治疗。
