Longitudinal Immune Responses and Gene Expression Profiles in Type 1 Leprosy Reactions
Longitudinal Immune Responses and Gene Expression Profiles in Type 1 Leprosy Reactions
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DOI：
10.1007/s10875-013-9979-x
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发表时间：
2014-02-01
影响因子：
9.1
通讯作者：
Ottenhoff, Tom H. M.
中科院分区：
文献类型：
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作者：
Geluk, Annemieke;van Meijgaarden, Krista E.;Ottenhoff, Tom H. M.
目的麻风病是一种由麻风分枝杆菌引起的慢性疾病，常伴有急性炎症反应。虽然至少50%的麻风病人会发生这种情况，并可能造成不可逆转的神经损伤，但没有实验室测试可用于早期诊断或预测反应。由于免疫和遗传宿主因素在麻风反应中至关重要，我们假设，与麻风反应相关的宿主衍生生物标志物的鉴定可以为新的测试提供基础，以促进及时的诊断和治疗，从而有助于防止组织damage.Methods麻风患者的纵向宿主反应，谁是受MDT治疗后的1型反应（T1 R）的影响，进行了前所未有的详细研究，检测细胞和体液免疫以及基因表达谱，以鉴定T1 R特异性生物标志物。与T1 R前相比，麻风患者在诊断T1 R时IFN-γ、IP-10、CXCL 9、IL-17 A和VEGF的产生增加，而在T1 R时观察到IL-10和G-CSF同时减少。细胞因子的变化与已知的调节性CD 39（+）CCL 4（+）和CD 25（高）T细胞亚群的减少一致。此外，RNA表达谱显示IFN诱导的基因，（V）EGF，和与细胞毒性T细胞反应相关的基因，（GNLY，GZMA/B，PRF 1）在T1 R期表达上调，而T细胞调节相关基因表达下调。干扰的T细胞调节以及IFN诱导的基因在T1 R中起重要作用，并提供潜在的T1 R特异性宿主生物标志物。
Purpose Leprosy, a chronic disease initiated by Mycobacterium leprae, is often complicated by acute inflammatory reactions. Although such episodes occur in at least 50 % of all leprosy patients and may cause irreversible nerve damage, no laboratory tests are available for early diagnosis or prediction of reactions. Since immune-and genetic host factors are critical in leprosy reactions, we hypothesize that identification of host-derived biomarkers correlated to leprosy reactions can provide the basis for new tests to facilitate timely diagnosis and treatment thereby helping to prevent tissue damage.Methods The longitudinal host response of a leprosy patient, who was affected by a type 1 reaction (T1R) after MDT-treatment, was studied in unprecedented detail, measuring cellular and humoral immunity and gene expression profiles to identify biomarkers specific for T1R.Results Cytokine analysis in response to M. leprae revealed increased production of IFN-gamma, IP-10, CXCL9, IL-17A and VEGF at diagnosis of T1R compared to before T1R, whereas a simultaneous decrease in IL-10 and G-CSF was observed at T1R. Cytokines shifts coincided with a reduction in known regulatory CD39(+)CCL4(+) and CD25(high) T-cell subsets. Moreover, RNA expression profiles revealed that IFN-induced genes, (V)EGF, and genes associated with cytotoxic T-cell responses (GNLY, GZMA/B, PRF1) were upregulated during T1R, whereas expression of T-cell regulation-associated genes were decreased.Conclusions These data show that increased inflammation, vasculoneogenesis and cytotoxicity, perturbed T-cell regulation as well as IFN-induced genes play an important role in T1R and provide potential T1R-specific host biomarkers.