Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency
Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency
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DOI：
10.1016/j.jaip.2019.06.011
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发表时间：
2019-11-01
影响因子：
9.4
通讯作者：
Baris, Safa
中科院分区：
文献类型：
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作者：
Kiykim, Ayca;Ogulur, Ismail;Baris, Safa
背景：脂多糖反应性米色锚定(LRBA)缺乏症表现为易感染、自身免疫和淋巴组织增殖。细胞毒性T淋巴细胞相关抗原4免疫球蛋白(Abatacept)作为针对其免疫功能紊乱的靶向治疗的远期疗效尚不确定。目的：了解LRBA缺乏症的临床和免疫学特征，以及abatacept治疗对控制不同疾病表现的远期疗效。方法：从不同的免疫学中心招募22例LRBA缺陷患者，并进行前瞻性随访。每3个月对18名服用阿巴贝特的患者进行一次长期临床和免疫学反应评估。结果：患者的平均年龄为13.4±7.9岁，随访时间为3.4±2.3岁。反复感染19例(86.4%)，免疫紊乱18例(81.8%)，淋巴组织增生16例(72.7%)。在16名患者中，阿巴塔塞特的长期益处被证明是完全控制了淋巴增殖和慢性腹泻，随后是免疫失调，最明显的是自身免疫性细胞减少。与每4周给药一次相比，每周或每隔一周给药一次对疾病的控制效果更好。没有出现与停药治疗相关的严重副作用。循环T滤泡辅助细胞频率被发现是疾病活动性的可靠生物标志物，在大多数受试者中，在戒断治疗后，这一比例下降。然而，在2例病情较重且对阿巴贝特治疗相对耐受的患者中，高循环T滤泡辅助细胞频率持续存在。结论：长期阿巴贝特治疗对大多数LRBA缺乏症患者有效。(C)2019年美国过敏、哮喘和免疫学学会
BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established.OBJECTIVE: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations.METHODS: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry.RESULTS: The mean age of the patients was 13.4 +/- 7.9 years, and the follow-up period was 3.4 +/- 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy.CONCLUSIONS: Long-term abatacept therapy is effective in most patients with LRBA deficiency. (C) 2019 American Academy of Allergy, Asthma & Immunology