Identification and bioinformatics analysis of key neutrophil genes in patients with primary antiphospholipid syndrome

doi:10.3969/j.issn.1674-490X.2022.01.002

Abstract

Abstract: Objective To screen key differential genes and identify the biological functions and signaling pathways involved in neutrophils from patients with primary antiphospholipid syndrome(APS)by bioinformatic methods. Methods RNA sequencing data of neutrophils from APS patients were downloaded from the GEO database, differentially expressed genes were screened by using the limma package in R language, and up- and down-regulated genes were subjected to gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis by clusterProfiler, respectively. Finally, protein-protein interaction network was constructed by STRING database and core genes in the network were calculated using cytoscape software. Results A total of 512 up-regulated genes and 473 down-regulated genes were obtained by limma package screening. Up-regulated genes were mainly involved in functions and pathways including regulation of innate immune response, neutrophil activation, inflammatory complex formation, etc. down-regulated genes were mainly involvedin functions and pathways including T cell activation, lymphocyte differentiation, lymphocyte activation, etc. IFIT1, IFI35, IFI3, CCL2, TLR8, FCGR1A were the core genes among the up-regulated genes. MYC, CD8A, FYN,CD28, LCK, GNB2L1 were the core genes among the down-regulated genes. Conclusion The core genes identified by bioinformatic methods may be the key targets for the immune effects of neutrophils in patients with primary antiphospholipid syndrome.

Key words: antiphospholipid syndrome, neutrophils, hub gene, immune effect

CLC Number:

R446

LIN Meiying, GAN Donghui, GAO Ying, WANG Zhengjie,CHEN Zhimin. Identification and bioinformatics analysis of key neutrophil genes in patients with primary antiphospholipid syndrome[J]. Journal of Hebei Medical College for Continuing Education, 2022, 39(1): 8-14.

References

[1] GARCIA D, ERKAN D. Diagnosis and management of the antiphospholipid syndrome[J]. N Engl J Med, 2018, 378(21): 2010-2021. DOI: 10.1056/NEJMra1705454.
[2] SCHREIBER K, SCIASCIA S, DE GROOT P G, et al. Antiphospholipid syndrome[J]. Nat Rev Dis Primers, 2018, 4: 17103. DOI: 10.1038/nrdp.2017.103.
[3] LU Y, DONG Y, ZHANG Y, et al. Antiphospholipid antibody-activated NETs exacerbate trophoblast and endothelial cell injury in obstetric antiphospholipid syndrome[J]. J Cell Mol Med, 2020, 24(12): 6690-6703. DOI: 10.1111/jcmm.15321.
[4] WIRESTAM L, ARVE S, LINGE P, et al. Neutrophils-important communicators in systemic lupus erythematosus and antiphospholipid syndrome[J]. Front Immunol, 2019, 10: 2734. DOI: 10.3389/fimmu.2019.02734.
[5] LI K N, DU Y X, LI L, et al. Bioinformatics approaches for anti-cancer drug discovery[J]. Curr Drug Targets, 2020, 21(1): 3-17. DOI: 10.2174/1389450120666190923162203.
[6] KNIGHT J S, MENG H, COIT P, et al. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target[J]. JCI Insight, 2017, 2(18): e93897. DOI: 10.1172/jci.insight.93897.
[7] NEGRINI S, PAPPALARDO F, MURDACA G, et al. The antiphospholipid syndrome: from pathophysiology to treatment[J]. Clin Exp Med, 2017, 17(3): 257-267. DOI: 10.1007/s10238-016-0430-5.
[8] DOBROWOLSKI C, ERKAN D. Treatment of antiphospholipid syndrome beyond anticoagulation[J]. Clin Immunol, 2019, 206: 53-62. DOI: 10.1016/j.clim.2018.03.001.
[9] XOURGIA E, TEKTONIDOU M G. Type I interferon gene expression in antiphospholipid syndrome: pathogenetic, clinical and therapeutic implications[J]. J Autoimmun, 2019, 104: 102311. DOI: 10.1016/j.jaut.2019.102311.
[10] PALLI E, KRAVVARITI E, TEKTONIDOU M G. Type I interferon signature in primary antiphospholipid syndrome: clinical and laboratory associations[J]. Front Immunol, 2019, 10: 487. DOI: 10.3389/fimmu.2019.00487.
[11] KIM B, YEON J W, LEE J H, et al. CCL2 mitigates cyclic AMP-suppressed Th2 immune response in human dendritic cells[J]. Allergy, 2020, 75(8): 2108-2111. DOI: 10.1111/all.14284.
[12] HURST J, PRINZ N, LORENZ M, et al. TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic cells[J]. Immunobiology, 2009, 214(8): 683-691. DOI: 10.1016/j.imbio.2008.12.003.
[13] SCHWARZER R, JIAO H P, WACHSMUTH L, et al. FADD and caspase-8 regulate gut homeostasis and inflammation by controlling MLKL-and GSDMD-mediated death of intestinal epithelial cells[J]. Immunity, 2020, 52(6): 978-993. DOI: 10.1016/j.immuni.2020.04.002.

[1]	. [J]. Journal of Hebei Medical College for Continuing Education, 2020, 37(4): 31-34.
[2]	WANG Jianguo,WANG Shuxian,LIANG Shuxin,ZHU Shanshan,LI Tiemin. Clinical value of Myocardial Enzyme in patients with rheumatoid arthritis [J]. Medical Reserch and Education, 2014, 31(3): 14-16.
[3]	CAO Lijun,YANG Jing,GENG Fengzhen,LI Huiqing,SHI Zheng,SHI Dongyan. Retrospective report of clinical characterizations of an Enterobacter cloacae carrying NDM-1 associated with urinary tract infection [J]. Medical Reserch and Education, 2014, 31(1): 33-36.
[4]	WANG Jianguo,WANG Shuxian,LIANG Shuxin,LI Tiemin. Clinical application of CysC and Hcy detection in diabetic nephropathy [J]. Medical Reserch and Education, 2013, 30(5): 32-34,45.
[5]	LIU Shuzhuo,WANG Shuxian,LI Wei. Application research of automated urine flowmetry UF - 1000i and optical microscopy in red cell morphology analysis [J]. Medical Reserch and Education, 2013, 30(3): 20-22.
[6]	DUAN Lin,WANG Shuxian,WANG Shuo. Screening analysis on pregnant women with Down’s syndrome (Report of 1 000 cases) [J]. Medical Reserch and Education, 2013, 30(3): 43-46.
[7]	. Clinical application of UF-1000i fully automatic urinary sediment analyzer in conventional cell counts of hydrothorax and ascites. [J]. Medical Reserch and Education, 2013, 30(1): 51-53.
[8]	. [J]. Medical Reserch and Education, 2012, 29(3): 49-52.
[9]	WANG Shuxian,MA Lei,FENG Huiqing,ZHANG Hewei. F/T ratio in breast cancer diagnosis and prognosis assessement of application [J]. Medical Reserch and Education, 2012, 29(3): 53-55.
[10]	. [J]. Medical Reserch and Education, 2011, 28(2): 89-91,103.
[11]	. The relationship between concentration of methamidophos and level of TNF-α in serum in acute methamidophos poisoned patients [J]. Medical Reserch and Education, 2010, 27(4): 42-43.
[12]	. [J]. Medical Reserch and Education, 2009, 26(6): 64-65,68.
[13]	. [J]. Medical Reserch and Education, 2009, 26(5): 41-.
[14]	. [J]. Medical Reserch and Education, 2009, 26(4): 20-21.
[15]	. [J]. Medical Reserch and Education, 2009, 26(2): 28-30.