Evolution and long-term outcomes of combined immunodeficiency due to CARMIL2 deficiency.
Evolution and long-term outcomes of combined immunodeficiency due to CARMIL2 deficiency.
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作者：
CARMIL 2中的双等位基因功能丧失突变导致与皮炎、炎性肠病（IBD）和EBV相关平滑肌肿瘤相关的联合免疫缺陷。该疾病的临床和免疫学特征以及长期随访和治疗方案以前尚未在大型队列中报道。我们试图确定CARMIL 2缺乏症的临床和免疫学特征以及控制不同疾病表现的长期治疗效果。在15例CARMIL 2缺陷患者中前瞻性评估了目前的表型、长期结局和治疗反应，其中包括13例新病例。分析了淋巴细胞亚群、蛋白表达、调节性T细胞（Treg）和循环T滤泡辅助细胞（cTFH）。进行三维（3D）迁移测定以确定T细胞形状。发病时的平均年龄为38±23个月。主要临床特征为皮肤表现（n=14，93%）、生长迟缓（n=10，67%）、反复感染（n =10，67%）、过敏症状（n=8，53%）、慢性腹泻（n=4，27%）和EBV相关平滑肌瘤（n=2，13%）。患者的记忆性CD 4 + T细胞、Treg和cTFH细胞比例降低。记忆B和NK细胞也减少。当在高密度3D胶原凝胶基质中迁移时，CARMIL 2缺陷型T细胞在CD 28共刺激后表现出减少的T细胞增殖和细胞因子产生以及正常形态。皮肤表现从特应性皮炎和脂溢性皮炎到银屑病样皮疹。IBD是最严重的临床表现，导致生长迟缓，需要多种干预治疗。所有患者均存活，中位随访时间为10.8年（范围：3-17年）。该队列提供了CARMIL 2缺乏症的临床和免疫学特征以及不同表现的长期随访。
Biallelic loss-of-function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV-related smooth muscle tumors. Clinical and immunological characterizations of the disease with long-term follow-up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long-term efficacy of treatment in controlling different disease manifestations. The presenting phenotypes, long-term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2-deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cTFH) cells were analyzed. Three-dimensional (3D) migration assay was performed to determine T-cell shape. Mean age at disease onset was 38±23 months. Main clinical features were skin manifestations (n=14, 93%), failure to thrive (n=10, 67%), recurrent infections (n=10, 67%), allergic symptoms (n=8, 53%), chronic diarrhea (n=4, 27%), and EBV-related leiomyoma (n=2, 13%). Patients had reduced proportions of memory CD4+ T cells, Treg, and cTFH cells. Memory B and NK cells were also decreased. CARMIL2-deficient T-cells exhibited reduced T-cell proliferation and cytokine production following CD28 co-stimulation and normal morphology when migrating in a high-density 3D collagen gel matrix. Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow-up of 10.8 years (range: 3–17 years). This cohort provides clinical and immunological features and long-term follow-up of different manifestations of CARMIL2 deficiency.
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影响因子：
3.4
作者：
Garcia-Prat, Marina;Alvarez-Sierra, Daniel;Martinez-Gallo, Monica
通讯作者：
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DOI：
10.1016/j.jaip.2019.06.011
发表时间：
2019-11-01
影响因子：
9.4
作者：
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影响因子：
9.1
作者：
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Feldman, Hagit Baris
DOI：
10.1073/pnas.0807309106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Bubier, Jason A.;Sproule, Thomas J.;Roopenian, Derry C.
通讯作者：
Roopenian, Derry C.
影响因子：
14.2
作者：
Rezaei, Nima;Hedayat, Mona;Nichols, Kim E.
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