The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency.
The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency.
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DOI：
10.1016/j.jaci.2014.12.1945
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Grimbacher B
中科院分区：
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作者：
Engelhardt KR;Gertz ME;Keles S;Schäffer AA;Sigmund EC;Glocker C;Saghafi S;Pourpak Z;Ceja R;Sassi A;Graham LE;Massaad MJ;Mellouli F;Ben-Mustapha I;Khemiri M;Kilic SS;Etzioni A;Freeman AF;Thiel J;Schulze I;Al-Herz W;Metin A;Sanal Ö;Tezcan I;Yeganeh M;Niehues T;Dueckers G;Weinspach S;Patiroglu T;Unal E;Dasouki M;Yilmaz M;Genel F;Aytekin C;Kutukculer N;Somer A;Kilic M;Reisli I;Camcioglu Y;Gennery AR;Cant AJ;Jones A;Gaspar BH;Arkwright PD;Pietrogrande MC;Baz Z;Al-Tamemi S;Lougaris V;Lefranc G;Megarbane A;Boutros J;Galal N;Bejaoui M;Barbouche MR;Geha RS;Chatila TA;Grimbacher B
DOCK 8突变导致联合免疫缺陷（CID），也被归类为常染色体隐性高IgE综合征（HIES）。识别CID / HIES患者具有临床重要性，因为其预后和管理存在差异。定义将DOCK 8缺陷与其他形式的HIES和CID区分开来的临床特征;研究DOCK 8缺陷的突变谱;并报告特定临床发现的频率。研究了来自60个CID家族的82名患者，其中64名患者具有DOCK 8突变，18名患者没有DOCK 8突变。支持向量机用于比较来自35名DOCK 8缺陷患者与10名无DOCK 8突变的AR-HIES患者和64名STAT 3突变患者的临床数据。DOCK 8缺陷患者的中位IgE为5，201 IU，高嗜酸性粒细胞水平通常至少为800/µl（92%的患者），IgM水平较低（62%）。约20%的患者淋巴细胞减少，主要是由于低CD 4+和CD 8 + T细胞。不到一半的受试者对回忆抗原产生正常的特异性抗体反应。经常观察到细菌（84%）、病毒（78%）和真菌（70%）感染。皮肤肿胀（60%）和过敏（73%）是常见的临床问题。与STAT 3缺陷相反，很少有肺囊肿，骨折和出牙问题。死亡率很高（34%）。五个临床特征的组合有助于区分DOCK 8突变患者与STAT 3突变患者。DOCK 8缺乏症可能出现在患有严重病毒感染、过敏和/或低IgM水平的患者中，这些患者被诊断为HIES加嗜酸性粒细胞增多症和上呼吸道感染，但没有肺实质异常、乳牙保留和轻微创伤骨折。
Mutations in DOCK8 cause a combined immunodeficiency (CID) also classified as autosomal-recessive hyper-IgE syndrome (HIES). Recognizing patients with CID / HIES is of clinical importance due to a difference in prognosis and management. Define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs; study the mutational spectrum of DOCK8 deficiency; and report on the frequency of specific clinical findings. Eighty-two patients from 60 families with CID and the phenotype of autosomal-recessive HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with 10 AR-HIES patients without a DOCK8 mutation and 64 patients with STAT3 mutations. DOCK8-deficient patients had a median IgE of 5,201 IU, high eosinophil levels of usually at least 800/µl (92% of patients), and low levels of IgM (62%). About 20% of patients were lymphopenic, mainly due to low CD4+ and CD8+ T cells. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). A combination of five clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations. DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels, who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures.