Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate
Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate
复制标题
苏丹内脏利什曼病患者葡萄糖酸锑钠治疗前后的表达谱
DOI：
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
H. S. Mohamed
中科院分区：
文献类型：
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作者：
Mohamed A. M. Salih;Mohamed A. M. Salih;M. Fakiola;Paul A. Lyons;B. Younis;Ahmed Eleojo Musa;A. Elhassan;Denise Anderson;Genevieve Syn;Muntaser E Ibrahim;Jenefer M. Blackwell;Jenefer M. Blackwell;H. S. Mohamed
Visceral leishmaniasis (VL) in Sudan caused by Leishmania donovani is fatal in susceptible individuals if untreated. Treatment with sodium stibogluconate (SSG) leads to post‐kala‐azar dermal leishmaniasis (PKDL) in 58% of patients. Here, Affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (N=9 paired samples) pre‐ and post‐treatment with SSG. Using the Bioconductor package limma, 438 genes from 28 869 post‐quality‐control probe sets were differentially expressed (Pnominal≤.02) post‐ vs pretreatment. Canonical pathway analysis using Ingenuity Pathway Analysis™ identified “role of nuclear factor of activated T‐cell in regulation of immune response” (Pnominal=1.35×10−5; PBH‐adjusted=4.79×10−3), “B‐cell development” (Pnominal=2.04×10−4; PBH‐adjusted=.024), “Fcγ receptor‐mediated phagocytosis in macrophages and monocytes” (Pnominal=2.04×10−4; PBH‐adjusted=.024) and “OX40 signalling” (Pnominal=2.82×10−4; PBH‐adjusted=.025) as pathways differentially regulated post‐ vs pretreatment. Major network hub genes included TP53, FN1, MYC, BCL2, JUN, SYK, RUNX2, MMP1 and ACTA2. Top endogenous upstream regulators included IL‐7 (P=2.28×10−6), TNF (P=4.26×10−6), Amyloid Precursor Protein (P=4.23×10−5) and SPI1/PI.1 (P=1.17×10−7). Top predicted chemical drug regulators included the flavonoid genistein (P=4.56×10−7) and the quinoline alkaloid camptothecin (P=5.14×10−5). These results contribute to our understanding of immunopathology associated with VL and response to SSG treatment. Further replication could identify novel therapeutic strategies that improve on SSG treatment and reduce the likelihood of progression to PKDL.
影响因子：
20.3
作者：
Kiani, A;García-Cózar, FJ;Rao, A
通讯作者：
Rao, A