Well-organized Granuloma Lymphadenitis Tuberculosis Expressed Lower Macrophage Migration Inhibitory Factor (MIF) Score Compared to the Poorly-organized Granuloma

Hamsu Kadriyan, Fathul Djannah, Philip Habib, Triana Diah Cahyawati, Nurhidayati Siddik


BACKGROUND: The case of extra-pulmonary tuberculosis (EPTB) is common and the most type of extra-pulmonary tuberculosis found is lymphadenitis TB (LnTB). Macrophage migration inhibitory factor (MIF) is correlated with TB, and low level of MIF was correlated to Mycobacterium TB bacteremia. Deficiency of MIF macrophage is known to be correlated to the increased of a lung pathology; however, its role on pathogenesis LnTB remains unclear. Hence, this study was conducted to analyze the correlation of MIF in several type of granuloma organization in LnTB.

METHODS: Block paraffin of the lymphoid tissue infected with M. Tuberculosis were analyzed with immunohistochemistry (IHC) to assess the MIF expression, by counting the immunoreactivity score (IRS) according to the intensity of stained cells and the level of staining. The histopathology type of LnTB was divided into well-organized granuloma (WOG) and poorly-organized granuloma (POG) based on the granuloma characteristics.

RESULTS: Among 100 tissues samples that fulfilled the study criteria, WOG was found in 51% cases. MIF was expressed mild positive in 21% samples, on the other hand, 79% was not expressed. There was a significant difference of MIF negative, as was found in 98% of WOG group while only 59% was found in POG group (p<0.001).

CONCLUSION: There is a significant correlation between MIF expression with the type of granuloma organization in LnTB. The expression of MIF in WOG group is mostly negative, as well as a half of the POG group. This results may suggests that MIF plays a role in the pathogenesis of granuloma formation in LnTB.

KEYWORDS: MIF, lymphadenitis TB, WOG, POG, immunohistochemistry

Full Text:



Yunda DK, Witjaksono F, Nurwidya FM. Correlation between protein intake, fat free mass, and total lymphocyte count with quality of life in pulmonary tuberculosis patients undergoing intensive phase treatment in Pekanbaru, Riau Province. Mol Cell Biomed Sci. 2020; 4(3): 128-34, CrossRef.

World Health Organization (WHO). WHO TB Report 2021. Geneva: WHO; 2021, article.

Fang Y, Zhou Q, Li L, Zhou Y, Sha W. Epidemiological characteristics of extrapulmonary tuberculosis patients with or without pulmonary tuberculosis. Epidemiol Infect. 2022; 150: e158, CrossRef.

Kadriyan H, Lestarini IA, Djannah F, Andiwijaya FR. Three rare case of otolaryngology tuberculosis: a report of extra-pulmonary tuberculosis cases in the larynx, tonsil and parotid. Adv Health Sci Res. In: Proceedings of the 2nd Global Health and Innovation in conjunction with 6th ORL Head and Neck Oncology Conference (ORLHN 2021). Dordrecht: Atlantis Press International BV; 2022, CrossRef.

Djannah F, Massi MH, Hatta M, Bukhari A, Hasanah I. Profile and histopathology features of top three cases of extra pulmonary tuberculosis (EPTB) in West Nusa Tenggara: a retrospective cross-sectional study. Ann Med Surg (Lond). 2022: 75; 103318, CrossRef.

Muluye D, Biadgo B, Woldegerima E, Ambachew A. Prevalence of tuberculous lymphadenitis in Gondar University Hospital, Northwest Ethiopia. BMC Public Health. 2013; 13: 435, CrossRef.

Silva Miranda M, Breiman A, Allain S, Deknuydt F, Altare F. The tuberculous granuloma: an unsuccessful host defence mechanism providing a safety shelter for the bacteria? Clin Dev Immunol. 2012; 2012: 139127, CrossRef.

McCaffrey EF, Donato M, Keren L, Chen Z, Delmastro A, Fitzpatrick MB, et al. The immunoregulatory landscape of human tuberculosis granulomas. Nat Immunol. 2022; 23(2): 318-29, CrossRef.

Tahseen S, Ambreen A, Ishtiaq S, Khanzada FM, Safdar N, Sviland L, et al. The value of histological examination in the diagnosis of tuberculous lymphadenitis in the era of rapid molecular diagnosis. Sci Rep. 2022; 12(1): 8949, CrossRef.

Firmanti SC, Triasih R, Wibawa T, Haryana SM. Interferon-g-inducible protein 10 for diagnosis of tuberculosis in children. Indones Biomed J. 2020; 12(1): 19-26, CrossRef.

Sulastri N, Alisjahbana B, Livia B, Sahiratmadja E. Higher neutrophil-lymphocyte ratio in TB/HIV co-infection compared to pulmonary tuberculosis. Indones Biomed J. 2021; 13(4): 375-82, CrossRef.

Syafira SZ, Zavitri NG, Yan S, Sribudiani Y, Lezhava A, Chaidir L. Positivity rate of pyrosequencing to diagnose drug-resistant tuberculosis directly from sputum with different bacterial load. Indones Biomed J. 2020;12(4); 313-9, CrossRef.

Gandhare A, Mahashur A. Tuberculosis of the lymph nodes: many facets, many hues. Astrocyte. 2017; 4(2): 80-6, CrossRef.

Abebe F, Bjune G. The protective role of antibody responses during Mycobacterium tuberculosis infection. Clin Exp Immunol. 2009; 157(2): 235-43, CrossRef.

Das R, Koo MS, Kim BH, Jacob ST, Subbian S, Yao J, et al. Macrophage migration inhibitory factor (MIF) is a critical mediator of the innate immune response to Mycobacterium tuberculosis. Proc Natl Acad Sci USA. 2013; 110(32): E2997-3006, CrossRef.

Grieb G, Merk M, Bernhagen J, Bucala R. Macrophage migration inhibitory factor (MIF): a promising biomarker. Drug News Perspect. 2010; 23(4): 257-64, CrossRef.

Chuang YC, Chen HR, Yeh TM. Pathogenic roles of macrophage migration inhibitory factor during dengue virus infection. Mediators Inflamm. 2015; 2015: 547094, CrossRef.

Xu L, Li Y, Sun H, Zhen X, Qiao C, Tian S, et al. Current developments of macrophage migration inhibitory factor (MIF) inhibitors. Drug Discov Today. 2013; 18(11-12): 592-600, CrossRef.

Wang Q, Han W, Niu J, Sun B, Dong W, Li G. Prognostic value of serum macrophage migration inhibitory factor levels in pulmonary tuberculosis. Respir Res. 2019; 20(1): 50, CrossRef.

McClean CM, Tobin DM. Macrophage form, function, and phenotype in mycobacterial infection: lessons from tuberculosis and other diseases. Pathog Dis. 2016; 74(7): ftw068, CrossRef.

Yulizal OK, Lelo A, Ilyas S, Kusumawati RL. The effect of snakehead fish extract supplementation to first-line eradication regimen on macrophage migration inhibitory factor (MIF) expression in rats induced by Helicobacter pylori infection. J Adv Vet Anim Res. 2020; 7(2): 209-17, CrossRef.

Wang J, Sheng B, Li X, Sun J, Shi L, Wei W, et al. Migration inhibitory factor in spinal tuberculosis: -173G/C polymorphisms, and transcript and protein levels in a northern province of China. Medicine (Baltimore). 2020; 99(30): e21331, CrossRef.

Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003; 3(10): 791-800, CrossRef.

Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M, et al. Macrophage migration inhibitory factor in rheumatoid arthritis: evidence of proinflammatory function and regulation by glucocorticoids. Arthritis Rheum. 1999; 42(8): 1601-8, PMID.

De Souza MB, Curioni OA, Kanda JL, De Carvalho MB. Serum and salivary macrophage migration inhibitory factor in patients with oral squamous cell carcinoma. Oncol Lett. 2014; 8(5): 2267-75, CrossRef.

Kibiki GS, van der Ven AJ, Geurts-Moespot A, Shao J, Calandra T, Sweep FC, et al. Serum and BAL macrophage migration inhibitory factor levels in HIV infected Tanzanians with pulmonary tuberculosis or other lung diseases. Clin Immunol. 2007; 123(1): 60-5, CrossRef.

Yamada G, Shijubo N, Takagi-Takahashi Y, Nishihira J, Mizue Y, Kikuchi K, et al. Elevated levels of serum macrophage migration inhibitory factor in patients with pulmonary tuberculosis. Clin Immunol. 2002; 104(2): 123-7, CrossRef.

Wiersinga WJ, Calandra T, Kager LM, van der Windt GJ, Roger T, le Roy D, et al. Expression and function of macrophage migration inhibitory factor (MIF) in melioidosis. PLoS Negl Trop Dis. 2010; 4(2): e605, CrossRef.

Watarai H, Nozawa R, Tokunaga A, Yuyama N, Tomas M, Hinohara A, et al. Posttranslational modification of the glycosylation inhibiting factor (GIF) gene product generates bioactive GIF. Proc Natl Acad Sci USA. 2000; 97(24): 13251-6, CrossRef.

Schindler L, Dickerhof N, Hampton MB, Bernhagen J. Post-translational regulation of macrophage migration inhibitory factor: Basis for functional fine-tuning. Redox Biol. 2018; 15: 135-42, CrossRef.

Ambreen A, Khaliq A, Naqvi SZH, Tahir A, Mustafa M, Chaudhary SU, et al. Host biomarkers for monitoring therapeutic response in extrapulmonary tuberculosis. Cytokine. 2021; 142: 155499, CrossRef.

Liu A, Li J, Bao F, Zhu Z, Feng S, Yang J, et al. Single nucleotide polymorphisms in cytokine MIF gene promoter region are closely associated with human susceptibility to tuberculosis in a southwestern province of China. Infect Genet Evol. 2016; 39: 219-24, CrossRef.

Li Y, Zeng Z, Deng S. Study of the relationship between human MIF level, MIF-794CATT5-8 microsatellite polymorphism, and susceptibility of tuberculosis in Southwest China. Braz J Infect Dis. 2012; 16(4): 383-6, CrossRef.

Gehlen M, Costa ERD, Rossetti MLR, Silva DR. Macrophage migration inhibitory factor -173 G>C single nucleotide polymorphism and its association with active pulmonary tuberculosis. PLoS One. 2020; 15(6): e0234565, CrossRef.

Olivieri C, Bargagli E, Inghilleri S, Campo I, Cintorino M, Rottoli P. Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients. Exp Lung Res. 2016; 42(5): 263-6, CrossRef.

DOI: https://doi.org/10.18585/inabj.v15i1.2070

Copyright (c) 2023 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Indexed by:






The Prodia Education and Research Institute