Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate-to-severe disease.
Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate-to-severe disease.
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对成人特应性皮炎异质性的洞察来自中到重度疾病患者的循环生物标记物分析。
DOI：
10.1111/exd.14389
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发表时间：
2021-11
影响因子：
3.6
通讯作者：
Guttman-Yassky E
中科院分区：
文献类型：
--
作者：
Sims JT;Chang CY;Higgs RE;Engle SM;Liu Y;Sissons SE;Rodgers GH;Simpson EL;Silverberg JI;Forman SB;Janes JM;Colvin SC;Guttman-Yassky E
特应性皮炎（AD）是一种异质性全身性炎症性皮肤病，与免疫反应失调、屏障功能障碍和感觉神经激活有关。为了表征AD患者中的循环炎症特征和潜在的全身性疾病异质性，分析了baricitinib（JAHG）II期研究中患有中度至重度AD的成人患者（N = 123）的血液样本。使用高通量和超灵敏蛋白质组学平台评价了131种标志物的基线水平，基于这些外周标志物生成患者聚类。我们实施了一种新的聚类再现性方法来验证我们研究中的聚类结果，并使用公开的AD生物标志物数据集（73个标志物，N = 58例患者）来验证我们的发现。聚类再现性分析通过k均值证明了2个聚类的最佳一致性，在独立患者队列中验证了该聚类结果的再现性。这些独特的JAHG患者亚组在多种免疫应答（高炎症）中具有升高的促炎介质，特别是TNFβ、MCP-3和IL-13，或具有较低水平的炎症生物标志物（低炎症）。与低炎症亚组相比，高炎症亚组与更大的基线疾病严重程度相关，表现为更大的EASI、SCORAD指数、瘙痒NRS和DLQI评分。非裔美国患者主要与高炎症亚组和基线疾病严重程度增加相关。在中重度AD患者中，通过检测2个疾病亚组、种族组之间的差异聚集和超出传统极化免疫反应的促炎介质升高来确定异质性。可能需要针对多种促炎细胞因子的治疗策略来解决这种异质性。
Atopic dermatitis (AD) is a heterogeneous systemic inflammatory skin disease associated with dysregulated immune responses, barrier dysfunction and activated sensory nerves. To characterize circulating inflammatory profiles and underlying systemic disease heterogeneity within AD patients, blood samples from adult patients (N = 123) with moderate‐to‐severe AD in a phase 2 study of baricitinib (JAHG) were analysed. Baseline levels of 131 markers were evaluated using high‐throughput and ultrasensitive proteomic platforms, patient clusters were generated based on these peripheral markers. We implemented a novel cluster reproducibility method to validate cluster outcomes within our study and used publicly available AD biomarker data set (73 markers, N = 58 patients) to validate our findings. Cluster reproducibility analysis demonstrated best consistency for 2 clusters by k‐means, reproducibility of this clustering outcome was validated in an independent patient cohort. These unique JAHG patient subgroups either possessed elevated pro‐inflammatory mediators, notably TNFβ, MCP‐3 and IL‐13, among a variety of immune responses (high inflammatory) or lower levels of inflammatory biomarkers (low inflammatory). The high inflammatory subgroup was associated with greater baseline disease severity, demonstrated by greater EASI, SCORAD Index, Itch NRS and DLQI scores, compared with low inflammatory subgroup. African‐American patients were predominantly associated with the high inflammatory subgroup and increased baseline disease severity. In patients with moderate‐to‐severe AD, heterogeneity was identified by the detection of 2 disease subgroups, differential clustering amongst ethnic groups and elevated pro‐inflammatory mediators extending beyond traditional polarized immune responses. Therapeutic strategies targeting multiple pro‐inflammatory cytokines may be needed to address this heterogeneity.
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DOI：
10.1111/bjd.17088
发表时间：
2019-03
期刊：
The British journal of dermatology
影响因子：
--
作者：
McAleer MA;Jakasa I;Hurault G;Sarvari P;McLean WHI;Tanaka RJ;Kezic S;Irvine AD
通讯作者：
Irvine AD
DOI：
10.1016/j.jaci.2015.05.049
发表时间：
2015-10
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Czarnowicki T;Esaki H;Gonzalez J;Malajian D;Shemer A;Noda S;Talasila S;Berry A;Gray J;Becker L;Estrada Y;Xu H;Zheng X;Suárez-Fariñas M;Krueger JG;Paller AS;Guttman-Yassky E
通讯作者：
Guttman-Yassky E
影响因子：
8.6
作者：
Ellis, CN;Stevens, SR;Cooper, KD
通讯作者：
Cooper, KD
影响因子：
3.9
作者：
Mansouri Y;Guttman-Yassky E
通讯作者：
Guttman-Yassky E
影响因子：
82.9
作者：
Ghoreschi, K;Thomas, P;Röcken, M
通讯作者：
Röcken, M