Genetic diagnosis of immune dysregulation can lead to targeted therapy for interstitial lung disease: A case series and single center approach.
Genetic diagnosis of immune dysregulation can lead to targeted therapy for interstitial lung disease: A case series and single center approach.
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免疫失调的基因诊断可导致间质性肺病的靶向治疗：病例系列和单中心方法。
DOI：
10.1002/ppul.25924
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发表时间：
2022-07
影响因子：
3.1
通讯作者：
Casey, Alicia
中科院分区：
文献类型：
--
作者：
Wobma, Holly;Perkins, Ryan;Bartnikas, Lisa;Dedeoglu, Fatma;Chou, Janet;Vleugels, Ruth Ann;Lo, Mindy S.;Janssen, Erin;Henderson, Lauren A.;Whangbo, Jennifer;Vargas, Sara O.;Fishman, Martha;Krone, Katie A.;Casey, Alicia
近年来，越来越多的单基因疾病被描述为免疫失调的特征。这些“原发性免疫调节障碍”的一个子集可导致严重的间质性肺病，通常在儿童晚期或青春期被发现。肺部门诊患者可能有长期复杂的病史，但缺乏统一的遗传诊断。对于肺科医生来说，认识到提示多系统免疫失调的特征并启动基因检查是至关重要的，因为基于潜在遗传学的靶向治疗可能会阻止甚至逆转肺部疾病的进展。通过这种方法，我们中心已经能够诊断和治疗一组由影响免疫调节的基因缺陷引起的间质性肺病患者。在这里，我们提出了与三种不同途径的致病变异相关的代表性病例，并总结了疾病的表现和治疗方法。最后，我们讨论了我们对诊断和管理这些复杂的危及生命的慢性疾病的突出挑战的看法。
In recent years, a growing number of monogenic disorders have been described that are characterized by immune dysregulation. A subset of these “primary immune regulatory disorders” can cause severe interstitial lung disease, often recognized in late childhood or adolescence. Patients presenting to pulmonary clinic may have long and complex medical histories, but lack a unifying genetic diagnosis. It is crucial for pulmonologists to recognize features suggestive of multisystem immune dysregulation and to initiate genetic workup, since targeted therapies based on underlying genetics may halt or even reverse pulmonary disease progression. Through such an approach, our center has been able to diagnose and treat a cohort of patients with interstitial lung disease from gene defects that affect immune regulation. Here we present representative cases related to pathogenic variants in three distinct pathways and summarize disease manifestations and treatment approaches. We conclude with a discussion of our perspective on the outstanding challenges for diagnosing and managing these complex life-threatening and chronic disorders.
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DOI：
10.1056/nejmoa1312625
发表时间：
2014-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Liu Y;Jesus AA;Marrero B;Yang D;Ramsey SE;Sanchez GAM;Tenbrock K;Wittkowski H;Jones OY;Kuehn HS;Lee CR;DiMattia MA;Cowen EW;Gonzalez B;Palmer I;DiGiovanna JJ;Biancotto A;Kim H;Tsai WL;Trier AM;Huang Y;Stone DL;Hill S;Kim HJ;St Hilaire C;Gurprasad S;Plass N;Chapelle D;Horkayne-Szakaly I;Foell D;Barysenka A;Candotti F;Holland SM;Hughes JD;Mehmet H;Issekutz AC;Raffeld M;McElwee J;Fontana JR;Minniti CP;Moir S;Kastner DL;Gadina M;Steven AC;Wingfield PT;Brooks SR;Rosenzweig SD;Fleisher TA;Deng Z;Boehm M;Paller AS;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
影响因子：
15.3
作者：
Gruber, Conor;Martin-Fernandez, Marta;Bogunovic, Dusan
通讯作者：
Bogunovic, Dusan
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
15.9
作者：
Jeremiah, Nadia;Neven, Benedicte;Rieux-Laucat, Frederic
通讯作者：
Rieux-Laucat, Frederic
DOI：
10.1084/jem.20200600
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lepelley A;Martin-Niclós MJ;Le Bihan M;Marsh JA;Uggenti C;Rice GI;Bondet V;Duffy D;Hertzog J;Rehwinkel J;Amselem S;Boulisfane-El Khalifi S;Brennan M;Carter E;Chatenoud L;Chhun S;Coulomb l'Hermine A;Depp M;Legendre M;Mackenzie KJ;Marey J;McDougall C;McKenzie KJ;Molina TJ;Neven B;Seabra L;Thumerelle C;Wislez M;Nathan N;Manel N;Crow YJ;Frémond ML
通讯作者：
Frémond ML