Role of MMP 9 in the diagnosis and management of pulmonary tuberculosis and its association with nutritional status

Authors

  • Aishwarya G. Warrier
  • Reshma Kumarchandra
  • Kuthethur Sudha
  • Bhat B. Jayashree
  • Yalla Durgarao

DOI:

https://doi.org/10.51248/.v41i1.530

Keywords:

MMP9, pulmonary tuberculosis, albumin, iron, DOTS therapy

Abstract

Introductionand Aim: Etiopathogenesis of Pulmonary tuberculosis(PTB), is well established. Yet, the mechanisms by which a treatment regimen brings about remodelling of the pulmonary tissue during recovery phase is not well understood. The involvement of matrix metalloproteinase in this regard is debated, due to its dual role, either in disseminating the disease due to lung cavitation or reducing the inflammation due to recruitment of macrophages to the lung granulomas. PTB is a disease also driven by undernourishment.This study focuses on the association of nutritional status of PTB patients in restoring healthy lung tissue, monitored by blood levels of albumin, iron and MMP9, during the course of intensive treatment.

Materials and Methods: Serum levels of MMP9, iron, Total protein and albumin were estimated in 30 PTB patients who visited the Directly Observed Treatment Short course (DOTS) Centre at Government Wenlock Hospital, Mangalore, Karnataka,India. Twenty controls were enrolled for comparative statistics. Samples were collected at baseline and after two months of DOTS treatment in case of patients.Pre-treatment and post treatment values were compared by paired t test.Student’s ‘t’ test was used for comparing parameters in controls and patients. Correlation between parameters was done by Pearson’s correlation test.

 

Results: A significant increase was observed in serum iron (P=0.002) and total protein(P=0.01) levels post treatment but there was no significance in the levels of MMP9. Further, serum MMP9 correlatednegatively with body weight, BMI and serum total protein levels, post treatment, which was statistically significant. No other correlations were significant.

Conclusion: We conclude that MMP9 neither seems to be a diagnostic marker nor a therapeutic target in the treatment of tuberculosis. Although serum iron appears to be a predictor of improved nutritional status post treatment, it probably may have a role in tissue remodelling independent of MMP-9.

Author Biographies

Aishwarya G. Warrier

Department of Biochemistry,Kasturba Medical College, Mangalore,Manipal Academy of

Higher Education, Manipal, India

Reshma Kumarchandra

Department of Biochemistry,Kasturba Medical College, Mangalore,Manipal Academy of

Higher Education, Manipal, India

Kuthethur Sudha

Department of Biochemistry,Kasturba Medical College, Mangalore,Manipal Academy of

Higher Education, Manipal, India

Bhat B. Jayashree

Medical Officer,RNTCP/DOTS Centre,Government Wenlock Hospital,Mangaluru,Karnataka,India

Yalla Durgarao

Department of Biochemistry,Kasturba Medical College, Mangalore,Manipal Academy of

Higher Education, Manipal, India

References

Elkington, P.T., Ugarte-Gil, C.A., Friedland, J.S. Matrix metalloproteinase in tuberculosis. Eur Respir J 2011;38: 456-464.

Jennifer, L.T., Jessica, M.H., Steven, A.D., Jolynn, M.T., Linda, S.I., Randall, J.B.,etal., Role of Matrix metalloproteinase 9 in Granuloma formation during Pulmonary Mycobacterium tuberculosis infection. Infect. Immun. 2006;74: 6135-6144.

Zarir, F. U. Tuberculosis in India. BMJ. 2015; 23:1-2.

Elkington,P.T. , Robert,K.N.,Joseph, J.B., Cecilia,M.O., Donna,E.H., Dylan,R.E., et al.,Mycobacterium tuberculosis, butnot vaccine BCG, specifically upregulates matrix metalloproteinase-1.Am J Respir Crit Care Med. 2005; 172: 1596-1604.

Elkington,P.T., Emerson, J.E., Lopez-Pascua, L.D., O'Kane, C.M., Horncastle, D.E, Boyle, J.J., et al.,Mycobacterium tuberculosis up-regulates matrix metalloproteinase-1 secretion from human airway epithelial cells via a p38 MAPK switch. J Immunol. 2005; 175: 5333-5340.

Elkington, P.T., Green, J.A., Emerson, J.E., Lopez-Pascua, L.D., Boyle, J.J., O'Kane, C.M., et al., Synergistic upregulation of epithelial cell matrix metalloproteinase-9 secretion in tuberculosis. Am J Respir Cell Mol Biol. 2007; 37: 431-437.

Zhu, X.W., Price, N.M., Gilman, R.H., Recarvarren, S., Friedland, J.S. Multinucleate giant cells release functionally unopposed matrix metalloproteinase-9 in vitro and in vivo. J Infect Dis. 2007; 196: 1076-1079.

Gupta, K.B., Gupta, R., Aterja, A., Verma, M., Vishvkarma, S. Tuberculosis and Nutrition. Lung India. 2009; 26: 9-16.

Lee, S.W., Kang, Y.A., Yoon, Y.S., Um, S.W., Lee, S.M., Yoo, C.G., et al.,The prevalence and evalution of Anemia associated with tuberculosis. J Korean Med Sci. 2006; 21: 1028-1032.

Shindang, J., Bot, Y., Ojo, O., Edeh, O., Essien, C., Bwende, E. Serum albumin/globulin ratio in tuberculosis and HIV patients any relationship? Mycobat Dis. 2016; 6: 199.

India TB Report, Revised National TB Control Programme. Annual Status Report. New Delhi: India Offset Press. 2018: p. 24.

RayBio Human MMP-9 ELISA Kit Protocol. Norcross, GA: Ray Biotech. 2016;p. 3.

Garcic, A. A highly sensitive, simple determination of serum iron using chromazurol B.Clin Chem Acta. 1979;94: 115.

Doumas, B.T., Watson, W.A., Biggs, H. G. Albumin standards and the measurement of serum albumin with bromocresol green. Clin Chem Acta. 971; 31:87.

Gornall,A.G., Bardawill,C.J., David, M.M. Determination of serum proteins by means of the biuret reaction. J Biol Chem. 1949; 177: 751.

Majeed, S., Singh, P., Sharma, N., Sharma, S. Role of matrix metalloproteinase-9 in progression of tuberculosis meningitis: a pilot study in patients at different stages of the disease. BMC Infectious diseases. 2016; 16: 722.

Esmedlyaeva,D.S., Alexeyeva,N.P., Sapozhnikova,N.V.,Dyakova,M. E.,Perova,T. L.,Kiryukhina,L.D.,etal., The system of matrix metalloproteinases and their role in patients with pulmonary tuberculosis.Biomed Khim. 2016; 62:593-598. [Article in Russian]

Singh, S., Maniakis-Grivas, G., Singh. U.K., Asher, R.M., Mauri, F., Elkington, P.T., et al.,Interleukin-17 Regulates Matrix Metalloproteinase activity in human pulmonary tuberculosis.J Pathol. 2018;244:311-322.

Quiding-Järbrink,M., Smith,D.A., BancroftG. J.Production of matrix metalloproteinases in response to mycobacterial infection. Infect Immun. 2001;69:5661-5670.

Sheen,P., O'Kane,C.M., Chaudhary,K., Tovar,M., Santillan,C., Sosa,J., etal.,High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation.Eur Respir J. 2009;33:134-141.

Nursyam, E.W., Amin, Z., Rumende, C.M. The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med Indones. 2006;38:3-5.

Mupere, E., Malone, L., Zalwango, S., Okwera, A., Nsereko, M., Tisch, D.J., et al., Tuberculosis Research Unit at Case Western Reserve University. Wasting among Uganda men with pulmonary tuberculosis is associated with linear regain in lean tissue mass during and after treatment in contrast to women with wasting who regain fat tissue mass: Prospective cohort study. BMC Infect Dis. 2014;14:24.

Naik, A.L., Rajan, M.G., Manjrekar, P.A., Shenoy, M.T., Shreelata, S., Srikantiah, R.M., et al., Effect of DOTS treatment on vitamin D levels in pulmonary tuberculosis. J Clin Diagn Res.2017; 11: BC18-BC22.

Hanrahan, C.F., Golub, J.E., Mohapi, L., Tshabangu, N., Modisenyane, T., Chaisson, R.E., et al.,Body Mass Index and risk of tuberculosis and death. AIDS.2010; 24:1501-1508.

Isanaka, S., Mugusi, F., Urassa, W., Willett, W.C., Bosch, R.J., Villamor, E., et al.,Iron deficiency and anemia predict mortality in patients with tuberculosis. J Nutr. 2012; 142: 350-357.

Roberts, P. D., Hoffbrand, A.V., Mollin, D. L. Iron and folate metabolism in tuberculosis. Br Med J. 1966;2:198-202

Khan,Z.H.,Warke, S. S. Effect of anti-tuberculosis drugs on levels of serum protein in pulmonary tuberculosis patients.IJPRS. 2012; 1: 94-100.

Santarpia, L., Grandone, I., Contaldo, F., Pasanisi, F. Butyryl cholinesterase marker as a prognostic marker: a review of the literature. J Cachexia Sarcopenia Muscle 2013; 4: 31-39.

Don, B.R., Kaysen, G. Serum Albumin: Relationship to inflammation and nutrition. Seminar in Dialysis. 2004; 6: 432-437.

Karyadi, E., Schultink, W., Nelwan, R.H., Gross, R., Amin, Z., Dolmans, W.M., et al.,Poor micronutrient status of active pulmonary tuberculosis patients in Indonesia. J. Nutr. 2000; 130: 2953-2958.

de Martino, M., Lodi, L., Galli, L., Chiappini, E. Immune response to mycobacterium tuberculosis: A Narrative Review.Front Pediatr. 2019; 7: 350.

Downloads

Published

2021-04-03

How to Cite

1.
Warrier AG, Kumarchandra R, Sudha K, Jayashree BB, Durgarao Y. Role of MMP 9 in the diagnosis and management of pulmonary tuberculosis and its association with nutritional status. Biomedicine [Internet]. 2021Apr.3 [cited 2021Apr.14];41(1):36-41. Available from: https://biomedicineonline.org/index.php/home/article/view/530

Issue

Section

Original Research Articles