The Complement and Coagulation Cascades Pathway is Associated with Acute Necrotizing Pancreatitis by Genomics and Proteomics Analysis

Overview

Journal J Inflamm Res

Publisher Dove Medical Press

Date 2022 Apr 21

PMID 35444447

Authors

Xinyu Zhang

Zenghui Li

Wei Liu

Juanjuan Du

Yun Liu

Ningjun Yu

Chao Liu

Mei Zeng

Xiaoming Zhang

Affiliations

Soon will be listed here.

Abstract

Purpose: Acute pancreatitis can be classified histologically as interstitial edema pancreatitis (IEP) or as acute necrotizing pancreatitis (ANP). ANP has a higher mortality and long-term or short-term sequelae than IEP. Therefore, this work aims to explore the differences in pathogenesis between ANP and IEP and it has great clinical importance for the treatment and prevention of ANP.

Methods: In this work, whole blood samples from IEP and ANP patients were analyzed by whole gene sequencing (WGS). Serum samples from IEP and ANP patients were evaluated via enzyme-linked immunosorbent assay (ELISA). Meanwhile, pancreatic tissues of IEP and ANP rat models were subjected to data independent acquisition (DIA) proteomics assays. Then, the WGS analysis and DIA proteomics assay data were analyzed comprehensively.

Results: Six pathways were found to be significantly different in the ANP/IEP groups through WGS analysis. DIA proteomics found eleven different pathways. In both assays, the complement and coagulation cascades pathway was the most significantly different ( < 0.01) pathway between the two groups. WGS analysis showed base mutations in ten genes in the complement and coagulation cascades pathway. These results were consistent with the ten proteins detected by DIA proteomics analysis, which were significantly upregulated in the ANP/IEP groups. In addition, five of these proteins, complement C3, complement Factor I, alpha-2-macroglobulin, complement C9, and serpin family C member 1, were successfully verified by parallel reaction monitoring analysis and ELISA.

Conclusion: C3, CFI, Am, C9, and Serpinc1, which belong to complement and coagulation cascades pathway, may promote pancreatic necrosis and aggravate the severity of ANP.

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References

Whitcomb D, LaRusch J, Krasinskas A, Klei L, Smith J, Brand R . Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis. Nat Genet. 2012; 44(12):1349-54. PMC: 3510344. DOI: 10.1038/ng.2466. View

Tegla C, Cudrici C, Patel S, Trippe 3rd R, Rus V, Niculescu F . Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res. 2011; 51(1):45-60. PMC: 3732183. DOI: 10.1007/s12026-011-8239-5. View

Merza M, Hartman H, Rahman M, Hwaiz R, Zhang E, Renstrom E . Neutrophil Extracellular Traps Induce Trypsin Activation, Inflammation, and Tissue Damage in Mice With Severe Acute Pancreatitis. Gastroenterology. 2015; 149(7):1920-1931.e8. DOI: 10.1053/j.gastro.2015.08.026. View

Ohlsson K, LAURELL C . The disappearance of enzyme-inhibitor complexes from the circulation of man. Clin Sci Mol Med. 1976; 51(1):87-92. DOI: 10.1042/cs0510087. View

Trikudanathan G, Wolbrink D, van Santvoort H, Mallery S, Freeman M, Besselink M . Current Concepts in Severe Acute and Necrotizing Pancreatitis: An Evidence-Based Approach. Gastroenterology. 2019; 156(7):1994-2007.e3. DOI: 10.1053/j.gastro.2019.01.269. View

Forsmark C, Vege S, Wilcox C . Acute Pancreatitis. N Engl J Med. 2016; 375(20):1972-1981. DOI: 10.1056/NEJMra1505202. View

Dudkina N, Spicer B, Reboul C, Conroy P, Lukoyanova N, Elmlund H . Structure of the poly-C9 component of the complement membrane attack complex. Nat Commun. 2016; 7:10588. PMC: 4742998. DOI: 10.1038/ncomms10588. View

GLYNN A, Milne C . Lysozyme and immune bacteriolysis. Nature. 1965; 207(5003):1309-10. DOI: 10.1038/2071309a0. View

Schmidt J, Rattner D, Lewandrowski K, Compton C, Mandavilli U, Knoefel W . A better model of acute pancreatitis for evaluating therapy. Ann Surg. 1992; 215(1):44-56. PMC: 1242369. DOI: 10.1097/00000658-199201000-00007. View

10.

Zhang L, Qiao Z, Feng H, Shen J . The early predictive role of complement C3 and C4 in patients with acute pancreatitis. J Clin Lab Anal. 2020; 34(5):e23205. PMC: 7246392. DOI: 10.1002/jcla.23205. View

11.

Ohlsson K . Elimination of 125-I-trypsin alpha-macroglobulin complexes from blood by reticuloendothelial cells in dogs. Acta Physiol Scand. 1971; 81(2):269-72. DOI: 10.1111/j.1748-1716.1971.tb04900.x. View

12.

Roberts R . Protease inhibitors of human plasma. Alpha-2-macroglobulin. J Med. 1985; 16(1-3):129-224. View

13.

Brown E . Complement receptors and phagocytosis. Curr Opin Immunol. 1991; 3(1):76-82. DOI: 10.1016/0952-7915(91)90081-b. View

14.

Banks P, Bollen T, Dervenis C, Gooszen H, Johnson C, Sarr M . Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2012; 62(1):102-11. DOI: 10.1136/gutjnl-2012-302779. View

15.

Roxvall L, Bengtson A, Sennerby L, Heideman M . Activation of the complement cascade by trypsin. Biol Chem Hoppe Seyler. 1991; 372(4):273-8. DOI: 10.1515/bchm3.1991.372.1.273. View

16.

Wilson C, Heads A, Shenkin A, Imrie C . C-reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis. Br J Surg. 1989; 76(2):177-81. DOI: 10.1002/bjs.1800760224. View

17.

Berends E, Kuipers A, Ravesloot M, Urbanus R, Rooijakkers S . Bacteria under stress by complement and coagulation. FEMS Microbiol Rev. 2014; 38(6):1146-71. DOI: 10.1111/1574-6976.12080. View

18.

den Dunnen J, Dalgleish R, Maglott D, Hart R, Greenblatt M, McGowan-Jordan J . HGVS Recommendations for the Description of Sequence Variants: 2016 Update. Hum Mutat. 2016; 37(6):564-9. DOI: 10.1002/humu.22981. View

19.

Schepers N, Bakker O, Besselink M, Ali U, Bollen T, Gooszen H . Impact of characteristics of organ failure and infected necrosis on mortality in necrotising pancreatitis. Gut. 2018; 68(6):1044-1051. DOI: 10.1136/gutjnl-2017-314657. View

20.

Balthazar E, Robinson D, Megibow A, Ranson J . Acute pancreatitis: value of CT in establishing prognosis. Radiology. 1990; 174(2):331-6. DOI: 10.1148/radiology.174.2.2296641. View