Tuberc Respir Dis.  2017 Apr;80(2):153-158. 10.4046/trd.2017.80.2.153.

Down-Regulation of Serum High-Mobility Group Box 1 Protein in Patients with Pulmonary Tuberculosis and Nontuberculous Mycobacterial Lung Disease

• Kim SY
• Koh WJ
• Park HY
• Jeon K
• Lee SY
• Yim JJ
• Shin SJ

• KMID: 2375984
• DOI: http://doi.org/10.4046/trd.2017.80.2.153

Abstract

BACKGROUND
Recently, increased levels of high-mobility group box 1 protein (HMGB1) have been identified in various inflammatory conditions and infections. However, no studies have evaluated the HMGB1 level in nontuberculous mycobacterial (NTM) lung disease, and compared it to mycobacterial lung disease.
METHODS
A total of 60 patients newly diagnosed with NTM lung disease, 44 culture-positive pulmonary tuberculosis (TB) patients, and 34 healthy controls, were included in this study. The serum HMGB1 concentrations were quantified using HMGB1 enzyme-linked immunosorbent assay kits.
RESULTS
Serum HMGB1 level in patients with pulmonary TB or NTM lung disease, was significantly lower than that of the healthy controls. In addition, the serum HMGB1 level in TB patients was significantly lower than patients with NTM lung disease. However, the levels in NTM patient subgroups did not differ according to the causative species, disease progression, and disease phenotype.
CONCLUSION
Although low levels of serum HMGB1 has the potential to be a marker of mycobacterial lung disease, these levels were unable to differentiate disease progression and disease phenotype in NTM lung diseases.

Keyword

HMGB1 Protein; Nontuberculous Mycobacteria; Tuberculosis

MeSH Terms

Disease Progression
Down-Regulation*
Enzyme-Linked Immunosorbent Assay
HMGB1 Protein
Humans
Lung Diseases*
Lung*
Nontuberculous Mycobacteria
Phenotype
Tuberculosis
Tuberculosis, Pulmonary*
HMGB1 Protein

Figure

• 

  Figure 1 Levels of serum high mobility group box chromosomal protein 1 (HMGB1). (A) Amount of HMGB1 in the sera of healthy controls (HC; n=34), patients with nontuberculous mycobacteria (NTM) lung disease (n=60), and tuberculosis (TB) patients (n=44). (B) HMGB1 levels according to etiology (Mycobacterium avium [n=20], M. intracellulare [n=20], M. abscessus [n=10], and M. massiliense [n=10]). (C) HMGB1 levels according to disease progression (stable [n=19] vs. progressive [n=41]). The data are presented as Tukey's box-and-whisker plots. **p<0.01, ***p<0.001 for the results of comparisons between patients and controls.

Reference

1. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007; 175:367–416. PMID: 17277290.

2. Stout JE, Koh WJ, Yew WW. Update on pulmonary disease due to non-tuberculous mycobacteria. Int J Infect Dis. 2016; 45:123–134. PMID: 26976549.

3. Kwon YS, Koh WJ. Diagnosis of pulmonary tuberculosis and nontuberculous mycobacterial lung disease in Korea. Tuberc Respir Dis. 2014; 77:1–5.

4. Ryu YJ, Koh WJ, Daley CL. Diagnosis and treatment of nontuberculous mycobacterial lung disease: clinicians' perspectives. Tuberc Respir Dis. 2016; 79:74–84.

5. Bustin M. Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. Mol Cell Biol. 1999; 19:5237–5246. PMID: 10409715.

6. O'Connor KA, Hansen MK, Rachal Pugh C, Deak MM, Biedenkapp JC, Milligan ED, et al. Further characterization of high mobility group box 1 (HMGB1) as a proinflammatory cytokine: central nervous system effects. Cytokine. 2003; 24:254–265. PMID: 14609567.

7. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002; 418:191–195. PMID: 12110890.

8. Abraham E, Arcaroli J, Carmody A, Wang H, Tracey KJ. HMG-1 as a mediator of acute lung inflammation. J Immunol. 2000; 165:2950–2954. PMID: 10975801.

9. Kosai K, Seki M, Yanagihara K, Nakamura S, Kurihara S, Izumikawa K, et al. Elevated levels of high mobility group box chromosomal protein-1 (HMGB-1) in sera from patients with severe bacterial pneumonia coinfected with influenza virus. Scand J Infect Dis. 2008; 40:338–342. PMID: 17918013.

10. Taniguchi N, Kawahara K, Yone K, Hashiguchi T, Yamakuchi M, Goto M, et al. High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum. 2003; 48:971–981. PMID: 12687539.

11. Magrys A, Paluch-Oles J, Koziol-Montewka M, Zaborowski T, Milanowski J, Maciejewska B. Evaluation of high-mobility group box 1 protein concentration in serum of patients with M. tuberculosis infection. Immunol Invest. 2013; 42:49–60. PMID: 23231044.

12. Zeng JC, Xiang WY, Lin DZ, Zhang JA, Liu GB, Kong B, et al. Elevated HMGB1-related interleukin-6 is associated with dynamic responses of monocytes in patients with active pulmonary tuberculosis. Int J Clin Exp Pathol. 2015; 8:1341–1353. PMID: 25973018.

13. Koh WJ, Jeon K, Lee NY, Kim BJ, Kook YH, Lee SH, et al. Clinical significance of differentiation of Mycobacterium massiliense from Mycobacterium abscessus. Am J Respir Crit Care Med. 2011; 183:405–410. PMID: 20833823.

14. Jeong BH, Jeon K, Park HY, Kim SY, Lee KS, Huh HJ, et al. Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2015; 191:96–103. PMID: 25393520.

15. Wang HY, Bang H, Kim S, Koh WJ, Lee H. Identification of Mycobacterium species in direct respiratory specimens using reverse blot hybridisation assay. Int J Tuberc Lung Dis. 2014; 18:1114–1120. PMID: 25189562.

16. Ryu YJ. Diagnosis of pulmonary tuberculosis: recent advances and diagnostic algorithms. Tuberc Respir Dis. 2015; 78:64–71.

17. Leylabadlo HE, Kafil HS, Yousefi M, Aghazadeh M, Asgharzadeh M. Pulmonary tuberculosis diagnosis: where we are? Tuberc Respir Dis. 2016; 79:134–142.

18. Danelishvili L, McGarvey J, Li YJ, Bermudez LE. Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells. Cell Microbiol. 2003; 5:649–660. PMID: 12925134.

19. Ulrichs T, Kaufmann SH. New insights into the function of granulomas in human tuberculosis. J Pathol. 2006; 208:261–269. PMID: 16362982.

20. Naumnik W, Nilklinska W, Ossolinska M, Chyczewska E. Serum levels of HMGB1, survivin, and VEGF in patients with advanced non-small cell lung cancer during chemotherapy. Folia Histochem Cytobiol. 2009; 47:703–709. PMID: 20430742.

21. Petrof G, Abdul-Wahab A, Proudfoot L, Pramanik R, Mellerio JE, McGrath JA. Serum levels of high mobility group box 1 correlate with disease severity in recessive dystrophic epidermolysis bullosa. Exp Dermatol. 2013; 22:433–435. PMID: 23711070.

22. Wang C, Gou SJ, Chang DY, Yu F, Zhao MH, Chen M. Association of circulating level of high mobility group box 1 with disease activity in antineutrophil cytoplasmic autoantibody-associated vasculitis. Arthritis Care Res (Hoboken). 2013; 65:1828–1834. PMID: 24591411.

23. Wang H, Yang H, Czura CJ, Sama AE, Tracey KJ. HMGB1 as a late mediator of lethal systemic inflammation. Am J Respir Crit Care Med. 2001; 164(10 Pt 1):1768–1773. PMID: 11734424.

24. Kim SY, Koh WJ, Kim YH, Jeong BH, Park HY, Jeon K, et al. Importance of reciprocal balance of T cell immunity in Mycobacterium abscessus complex lung disease. PLoS One. 2014; 9:e109941. PMID: 25295870.

25. Kim SY, Koh WJ, Park HY, Jeon K, Kwon OJ, Cho SN, et al. Changes in serum immunomolecules during antibiotic therapy for Mycobacterium avium complex lung disease. Clin Exp Immunol. 2014; 176:93–101. PMID: 24354934.

26. Yang H, Antoine DJ, Andersson U, Tracey KJ. The many faces of HMGB1: molecular structure-functional activity in inflammation, apoptosis, and chemotaxis. J Leukoc Biol. 2013; 93:865–873. PMID: 23446148.

27. Hernandez-Pando R, Barrios-Payan J, Mata-Espinosa D, Marquina-Castillo B, Hernandez-Ramirez D, Bottasso OA, et al. The role of high mobility group box 1 protein (HMGB1) in the immunopathology of experimental pulmonary tuberculosis. PLoS One. 2015; 10:e0133200. PMID: 26201072.

28. Koh WJ, Yu CM, Suh GY, Chung MP, Kim H, Kwon OJ, et al. Pulmonary TB and NTM lung disease: comparison of characteristics in patients with AFB smear-positive sputum. Int J Tuberc Lung Dis. 2006; 10:1001–1007. PMID: 16964791.

29. Kim YK, Hahn S, Uh Y, Im DJ, Lim YL, Choi HK, et al. Comparable characteristics of tuberculous and non-tuberculous mycobacterial cavitary lung diseases. Int J Tuberc Lung Dis. 2014; 18:725–729. PMID: 24903945.

30. Walzl G, Ronacher K, Hanekom W, Scriba TJ, Zumla A. Immunological biomarkers of tuberculosis. Nat Rev Immunol. 2011; 11:343–354. PMID: 21475309.

31. Kokkola R, Sundberg E, Ulfgren AK, Palmblad K, Li J, Wang H, et al. High mobility group box chromosomal protein 1: a novel proinflammatory mediator in synovitis. Arthritis Rheum. 2002; 46:2598–2603. PMID: 12384917.

32. Urbonaviciute V, Furnrohr BG, Weber C, Haslbeck M, Wilhelm S, Herrmann M, et al. Factors masking HMGB1 in human serum and plasma. J Leukoc Biol. 2007; 81:67–74. PMID: 17060363.

33. Higa F, Furugen M, Koide M, Karimata Y, Nabeya D, Iha Y, et al. Clinical evaluation of high mobility group box 1 protein in Legionella pneumophila pneumonia. J Infect Chemother. 2014; 20:289–292. PMID: 24679738.

34. van Zoelen MA, Laterre PF, van Veen SQ, van Till JW, Wittebole X, Bresser P, et al. Systemic and local high mobility group box 1 concentrations during severe infection. Crit Care Med. 2007; 35:2799–2804. PMID: 17901841.

35. Gaini S, Koldkjaer OG, Moller HJ, Pedersen C, Pedersen SS. A comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study. Crit Care. 2007; 11:R76. PMID: 17625012.

36. Angus DC, Yang L, Kong L, Kellum JA, Delude RL, Tracey KJ, et al. Circulating high-mobility group box 1 (HMGB1) concentrations are elevated in both uncomplicated pneumonia and pneumonia with severe sepsis. Crit Care Med. 2007; 35:1061–1067. PMID: 17334246.