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Association of High Mobility Group Box 1 Protein Levels with Sepsis and Outcomes in Newborns

Year 2024, Volume: 46 Issue: 1, 1 - 8, 16.01.2024
https://doi.org/10.20515/otd.1326982

Abstract

High mobility group box-1 protein (HMGB-1) acts as a potent pro-inflammatory cytokine that is actively secreted by innate immune cells and/or passively released by injured or damaged cells during the terminal phase of sepsis. Therefore, serum and tissue levels of HMGB1 are elevated during infection, especially during sepsis. In this study, we aimed to evaluate HMGB1 levels in neonatal sepsis and its association with septic shock and death. Fifty-three neonates with a clinical or proven diagnosis of sepsis were included in the study. Fifty-seven postnatal age-matched neonates without symptoms or signs of infection and receiving routine NICU care were included as controls. Twelve patients had proven sepsis and 6 patients had septic shock. The death occurred in five septic infants. HMGB1 levels were higher in neonates with sepsis compared with controls; patients with septic shock had higher HMGB1 levels compared with those without septic shock (p=0.002). Although non-survivors had higher HMGB1 levels compared to survivors, this was not statistically significant (p=0.086). HMGB1 levels decreased significantly three days after diagnosis in patients without septic shock (p=0.014) but remained elevated in patients with septic shock (p=0.465). A positive correlation was found between CRP and HMGB1 (p=0.008, r=0.252). HMGB1 is a sensitive marker for differentiating patients with sepsis from the non-septic group. The addition of HMGB1 to the group of inflammatory markers may be useful in the detection of patients with severe sepsis compared to the diagnosis of sepsis.

References

  • 1. Oza S, Lawn JE, Hogan DR, et al. Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000-2013. Bull World Health Organ. 2015; 93:19.
  • 2. Wiersinga WJ, Leopold SJ, Cranendonk DR, et al. Host innate immune responses to sepsis. Virulence. 2014;5(1):36-44.
  • 3. Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999;285:248-251.
  • 4. Yang H, Wang H, Czura CJ, et al. The cytokine activity of HMGB1. J Leukoc Biol 2005;78:1-8
  • 5. Yang H, Wang H, Tracey KJ. HMG-1 rediscovered as a cytokine. Shock. 2001;15:247-253.
  • 6. Andersson U, Wang H, Palmblad K, et al. High Mobility Group 1 Protein (HMG-1) Stimulates Proinflammatory Cytokine Synthesis in Human Monocytes. J Exp Med. 2000;192:565-570.
  • 7. Sundén-Cullberg J, Norrby-Teglund A, Rouhiainen A, et al. Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Critical care medicine. 2005;33(3):564-573.
  • 8. Karlsson S, Pettila V, Tenhunen J, et al. HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis. Intensive Care Med. 2008;4:1046-1053.
  • 9. European Medicines Agency (EMA). Report on the Expert Meeting on Neonatal and Paediatric Sepsis London: 2010. [updated 8 June 2010]. Available at: www.ema.europa.eu/en/documents/report/report-expert-meeting-neonatal-paediatricsepsis_en.pdf
  • 10. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2-8.
  • 11. Parkkinen J, Raulo E, Merenmies J, et al. Amphoterin, the 30- kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. J Biol Chem. 1993;268:19726-19738
  • 12. Huang LF, Yao YM, Dong N, et al. Association of highmobility group box-1 protein levels with sepsis and outcome of severelyburned patients. Cytokine. 2011;53:29-34.
  • 13. Angus DC, Yang L, Kong L, et al. Circulating high-mobility group box 1 (HMGB1) concentrations are elevated in both uncomplicated pneumonia and pneumonia with severe sepsis. Critical care medicine. 2007;35(4):1061-1067.
  • 14. Gaini S, Pedersen S, Koldkjaer O, et al. High mobility group box-1 protein in patients with suspected community-acquired infections and sepsis: a prospective study. Crit Care. 2007;11(2):1-10.
  • 15. Xin K, Sun J, Liu P, et al. Expression and significance of HMGB1 in patients with sepsis and effects on prognosis. All Life. 2020;13(1):164-170.
  • 16. Gaini S, Koldkjaer OG, Moller HJ,et al. A comparison of highmobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study. Crit Care. 2007;11(4)1-10.
  • 17. Gibot S, Massin F, Cravoisy A, et al. High-mobility group box 1 protein plasma concentrations during septic shock. Intensive Care Med. 2007;33(8) 1347-1353.
  • 18. Karakike E, Adami ME, Lada M, et al. Late peaks of HMGB1 and sepsis outcome: evidence for synergy with chronic inflammatory disorders. Shock. 2019;52:334-339.
  • 19. Yasuda T, Ueda T, Takeyama Y, et al. Significant increase of serum high-mobility group box chromosomal protein 1 levels in patients with severe acute pancreatitis. Pancreas. 2006;33:359-363.
  • 20. Charoensup J, Sermswan RW, Paeyao A, et al. High HMGB1 level is associated with poor outcome of septicemic melioidosis. Int. J. Infect. Dis. 2016;2:111-116.
  • 21. Tang Z, Jiang M, Ou-Yang Z, et al. High mobility group box 1 protein (HMGB1) as biomarker in hypoxia-induced persistent pulmonary hypertension of the newborn: a clinical and in vivo pilot study. Int J Med SCI. 2019; 16:1123-1131
  • 22. Baumbusch MA, Buhimschi CS, Oliver EA, Zhao G, Thung S, Rood K, Buhimschi IA. High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth, and the source may be the damaged fetal membranes. Cytokine. 2016 ;81:82-7.
  • 23. Nakamura T, Yamada S, Yoshioka T. Measurement of plasma concentration of high mobility group box1 (HMGB1) in early neonates and evaluation of its usefulness. Clin Chim Acta. 2012;413(1-2):237-9.
  • 24. Hebra A, Strange P, Egbert JM, et al. Intracellular cytokine production by fetal and adult monocytes. J Pediatr Surg. 2001;36(9):1321-1326.
  • 25. Schultz C, Rott C, Temming P, et al. Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants. Pediatr Res. 2002;51:317-322.
  • 26. Dembinski J, Behrendt D, Reinsberg J, Bartmann P. Endotoxinstimulated production of IL-6 and IL-8 is increased in short-term cultures of whole blood from healthy term neonates. Cytokine. 2002;18(2):116-119.
  • 27. Matoba N, Yu Y, Mestan K, et al. Differential patterns of 27 cord blood immune biomarkers across gestational age. Pediatrics. 2009;123(5):1320-1328.

Yenı̇Doğanlarda High Mobility Group Box 1 Protein Düzeylerı̇nin Sepsı̇s ve Sonuçlarıyla İlişkisi

Year 2024, Volume: 46 Issue: 1, 1 - 8, 16.01.2024
https://doi.org/10.20515/otd.1326982

Abstract

High mobility group box-1 protein (HMGB-1); sepsisin son fazında doğal bağışıklık hücreleri tarafından aktif olarak salgılanan ve/veya yaralı veya hasarlı hücreler tarafından pasif olarak salınan güçlü bir pro-inflamatuar sitokin olarak görev yapar. Bu nedenle, HMGB1'in serum ve doku seviyeleri enfeksiyon sırasında, özellikle sepsis sırasında yükselir. Bu çalışmada, yenidoğan sepsisinde HMGB1 seviyelerini ve septik şok ve ölümle ilişkisinin değerlendirilmesi amaçlandı. Klinik veya kanıtlanmış sepsis tanısı olan 53 yenidoğan çalışmaya dahil edildi. Enfeksiyon semptomu veya bulgusu olmayan ve rutin YYBÜ bakımı alan doğum sonrası yaşı eşleştirilmiş elli yedi yenidoğan kontrol olarak alındı. On iki hastada kanıtlanmış sepsis, 6 hastada septik şok vardı. Beş septik bebek kaybedildi. Sepsisli yenidoğanlarda HMGB1 düzeyleri kontrollere kıyasla daha yüksekti; septik şoklu hastalarda septik şok olmayanlara kıyasla daha yüksek HMGB1 düzeyleri vardı (p=0,002). Hayatta kalmayanların hayatta kalanlara kıyasla daha yüksek HMGB1 seviyelerine sahip olmasına rağmen, bu istatistiksel olarak anlamlı değildi (p=0,086). HMGB1 düzeyleri septik şoku olmayan hastalarda tanıdan üç gün sonra önemli ölçüde düşerken (p=0,014) septik şok gelişen hastalarda yüksek kaldı (p=0,465). CRP ile HMGB1 arasında pozitif bir korelasyon saptandı (p=0,008, r=0,252). HMGB1, sepsisli hastaları septik olmayan gruptan ayırmak için hassas bir belirteçtir. Enflamatuar belirteçler grubuna HMGB1'in eklenmesi, sepsis tanısına kıyasla ciddi sepsisli hastaların tespitinde faydalı olabilir.

Supporting Institution

YOK

References

  • 1. Oza S, Lawn JE, Hogan DR, et al. Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000-2013. Bull World Health Organ. 2015; 93:19.
  • 2. Wiersinga WJ, Leopold SJ, Cranendonk DR, et al. Host innate immune responses to sepsis. Virulence. 2014;5(1):36-44.
  • 3. Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999;285:248-251.
  • 4. Yang H, Wang H, Czura CJ, et al. The cytokine activity of HMGB1. J Leukoc Biol 2005;78:1-8
  • 5. Yang H, Wang H, Tracey KJ. HMG-1 rediscovered as a cytokine. Shock. 2001;15:247-253.
  • 6. Andersson U, Wang H, Palmblad K, et al. High Mobility Group 1 Protein (HMG-1) Stimulates Proinflammatory Cytokine Synthesis in Human Monocytes. J Exp Med. 2000;192:565-570.
  • 7. Sundén-Cullberg J, Norrby-Teglund A, Rouhiainen A, et al. Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Critical care medicine. 2005;33(3):564-573.
  • 8. Karlsson S, Pettila V, Tenhunen J, et al. HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis. Intensive Care Med. 2008;4:1046-1053.
  • 9. European Medicines Agency (EMA). Report on the Expert Meeting on Neonatal and Paediatric Sepsis London: 2010. [updated 8 June 2010]. Available at: www.ema.europa.eu/en/documents/report/report-expert-meeting-neonatal-paediatricsepsis_en.pdf
  • 10. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2-8.
  • 11. Parkkinen J, Raulo E, Merenmies J, et al. Amphoterin, the 30- kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. J Biol Chem. 1993;268:19726-19738
  • 12. Huang LF, Yao YM, Dong N, et al. Association of highmobility group box-1 protein levels with sepsis and outcome of severelyburned patients. Cytokine. 2011;53:29-34.
  • 13. Angus DC, Yang L, Kong L, et al. Circulating high-mobility group box 1 (HMGB1) concentrations are elevated in both uncomplicated pneumonia and pneumonia with severe sepsis. Critical care medicine. 2007;35(4):1061-1067.
  • 14. Gaini S, Pedersen S, Koldkjaer O, et al. High mobility group box-1 protein in patients with suspected community-acquired infections and sepsis: a prospective study. Crit Care. 2007;11(2):1-10.
  • 15. Xin K, Sun J, Liu P, et al. Expression and significance of HMGB1 in patients with sepsis and effects on prognosis. All Life. 2020;13(1):164-170.
  • 16. Gaini S, Koldkjaer OG, Moller HJ,et al. A comparison of highmobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study. Crit Care. 2007;11(4)1-10.
  • 17. Gibot S, Massin F, Cravoisy A, et al. High-mobility group box 1 protein plasma concentrations during septic shock. Intensive Care Med. 2007;33(8) 1347-1353.
  • 18. Karakike E, Adami ME, Lada M, et al. Late peaks of HMGB1 and sepsis outcome: evidence for synergy with chronic inflammatory disorders. Shock. 2019;52:334-339.
  • 19. Yasuda T, Ueda T, Takeyama Y, et al. Significant increase of serum high-mobility group box chromosomal protein 1 levels in patients with severe acute pancreatitis. Pancreas. 2006;33:359-363.
  • 20. Charoensup J, Sermswan RW, Paeyao A, et al. High HMGB1 level is associated with poor outcome of septicemic melioidosis. Int. J. Infect. Dis. 2016;2:111-116.
  • 21. Tang Z, Jiang M, Ou-Yang Z, et al. High mobility group box 1 protein (HMGB1) as biomarker in hypoxia-induced persistent pulmonary hypertension of the newborn: a clinical and in vivo pilot study. Int J Med SCI. 2019; 16:1123-1131
  • 22. Baumbusch MA, Buhimschi CS, Oliver EA, Zhao G, Thung S, Rood K, Buhimschi IA. High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth, and the source may be the damaged fetal membranes. Cytokine. 2016 ;81:82-7.
  • 23. Nakamura T, Yamada S, Yoshioka T. Measurement of plasma concentration of high mobility group box1 (HMGB1) in early neonates and evaluation of its usefulness. Clin Chim Acta. 2012;413(1-2):237-9.
  • 24. Hebra A, Strange P, Egbert JM, et al. Intracellular cytokine production by fetal and adult monocytes. J Pediatr Surg. 2001;36(9):1321-1326.
  • 25. Schultz C, Rott C, Temming P, et al. Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants. Pediatr Res. 2002;51:317-322.
  • 26. Dembinski J, Behrendt D, Reinsberg J, Bartmann P. Endotoxinstimulated production of IL-6 and IL-8 is increased in short-term cultures of whole blood from healthy term neonates. Cytokine. 2002;18(2):116-119.
  • 27. Matoba N, Yu Y, Mestan K, et al. Differential patterns of 27 cord blood immune biomarkers across gestational age. Pediatrics. 2009;123(5):1320-1328.
There are 27 citations in total.

Details

Primary Language English
Subjects Neonatology, Intensive Care
Journal Section ORİJİNAL MAKALE
Authors

Tuğba Barsan Kaya 0000-0003-0698-1850

Damla Güneş 0000-0002-8252-2368

Özge Aydemir 0000-0002-4106-0873

Özge Sürmeli Onay 0000-0002-7658-3594

Ayşe Neslihan Tekin 0000-0002-2993-5737

Publication Date January 16, 2024
Published in Issue Year 2024 Volume: 46 Issue: 1

Cite

Vancouver Barsan Kaya T, Güneş D, Aydemir Ö, Sürmeli Onay Ö, Tekin AN. Association of High Mobility Group Box 1 Protein Levels with Sepsis and Outcomes in Newborns. Osmangazi Tıp Dergisi. 2024;46(1):1-8.


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