Hepatic Involvement in Aicardi-Goutières Syndrome.
Hepatic Involvement in Aicardi-Goutières Syndrome.
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DOI：
10.1055/s-0040-1722673
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发表时间：
2021-12
期刊：
影响因子：
1.4
通讯作者：
Adang L
中科院分区：
文献类型：
--
作者：
Gavazzi F;Cross ZM;Woidill S;McMann JM;Rand EB;Takanohashi A;Ulrick N;Shults J;Vanderver AL;Adang L
Aicardi-Goutières综合征（AGS）是一种导致神经损伤的单基因I型干扰素病。持续干扰素激活的全身影响还不太清楚。已知肝脏炎症与新生儿形式的AGS相关，但整个生命周期中AGS相关肝炎的发病率尚不清楚。我们比较了自然病史数据，包括肝酶水平与炎症标志物（肝脏特异性自身抗体和干扰素信号基因表达[ISG]评分）。肝酶按超过正常上限（ULN）的倍数升高分类为正常或升高。最高升高被指定为肝炎，定义为丙氨酸氨基转移酶或丙氨酸氨基转移酶3倍ULN，或γ-谷氨酰转移酶2.5倍ULN。一个更大的队列被用来进一步描述肝脏异常的纵向发生率以及与年龄和基因型的相关性。在整个AGS队列（n = 102）中，76例（74.5%）肝酶升高，29例（28.4%）肝酶异常与肝炎水平一致。SAMHD 1突变与肝炎相关性较低（对数秩检验; p = 0.011）。肝炎与早发性疾病和小头畸形相关（对数秩检验;小头畸形p = 0.0401，年龄发作p = 0.0355）。虽然大多数受试者（n = 20/33）被发现有肝脏特异性自身抗体，但自身抗体或ISG评分与肝炎水平酶升高之间没有关联。总之，所有AGS基因型均与肝酶一过性升高和肝相关自身抗体的存在相关。这增加了我们对全身病理学AGS的了解。
Aicardi-Goutières syndrome (AGS) is a monogenic type-I interferonopathy that results in neurologic injury. The systemic impact of sustained interferon activation is less well characterized. Liver inflammation is known to be associated with the neonatal form of AGS, but the incidence of AGS-related hepatitis across lifespan is unknown. We compared natural history data including liver enzyme levels with markers of inflammation, (liver-specific autoantibodies and interferon signaling gene expression [ISG] scores). Liver enzymes were classified as normal or elevated by the fold increase over the upper limit of normal (ULN). The highest increases were designated as hepatitis, defined as aspartate-aminotransferase or alanine-aminotransferase threefold ULN, or gamma-glutamyl transferase 2.5-fold ULN. A larger cohort was used to further characterize the longitudinal incidence of liver abnormalities and the association with age and genotype. Across the AGS cohort (n = 102), elevated liver enzymes were identified in 76 individuals (74.5%) with abnormalities at a level consistent with hepatitis in 29 individuals (28.4%). SAMHD1 mutations were less likely to be associated with hepatitis (log-rank test; p = 0.011). Hepatitis was associated with early-onset disease and microcephaly (log-rank test; microcephaly p = 0.0401, age onset p = 0.0355). While most subjects (n = 20/33) were found to have liver-specific autoantibodies, there was no association between the presence of autoantibodies or ISG scores with hepatitis-level enzyme elevations. In conclusion, all genotypes of AGS are associated with transient elevations of liver enzymes and the presence of liver-associated autoantibodies. This adds to our growing understanding of the systemic pathology AGS.
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影响因子：
30.8
作者：
Rice GI;Del Toro Duany Y;Jenkinson EM;Forte GM;Anderson BH;Ariaudo G;Bader-Meunier B;Baildam EM;Battini R;Beresford MW;Casarano M;Chouchane M;Cimaz R;Collins AE;Cordeiro NJ;Dale RC;Davidson JE;De Waele L;Desguerre I;Faivre L;Fazzi E;Isidor B;Lagae L;Latchman AR;Lebon P;Li C;Livingston JH;Lourenço CM;Mancardi MM;Masurel-Paulet A;McInnes IB;Menezes MP;Mignot C;O'Sullivan J;Orcesi S;Picco PP;Riva E;Robinson RA;Rodriguez D;Salvatici E;Scott C;Szybowska M;Tolmie JL;Vanderver A;Vanhulle C;Vieira JP;Webb K;Whitney RN;Williams SG;Wolfe LA;Zuberi SM;Hur S;Crow YJ
通讯作者：
Crow YJ
影响因子：
3.1
作者：
Gilman AJ;Le AK;Zhao C;Hoang J;Yasukawa LA;Weber SC;Vierling JM;Nguyen MH
通讯作者：
Nguyen MH
影响因子：
2.3
作者：
Kim, Hanna;de Jesus, Adriana A.;Goldbach-Mansky, Raphaela
通讯作者：
Goldbach-Mansky, Raphaela
影响因子：
4.8
作者：
Shults, Justine;Ratcliffe, Sarah J.;Leonard, Mary
通讯作者：
Leonard, Mary
影响因子：
3.8
作者：
Adang, Laura A.;Frank, David B.;Vanderver, Adeline L.
通讯作者：
Vanderver, Adeline L.