Analysis of interleukin 7 and platelet-derived growth factor-BB mRNA expression as potential markers in erythema nodosum leprosum


Submitted: 18 June 2023
Accepted: 16 July 2023
Published: 12 September 2023
Abstract Views: 591
PDF: 306
HTML: 7
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

  • Fitri Kadarsih Banjar Department of Dermatology and Venereology, Faculty of Medicine Universitas Pattimura, Maluku; Doctorate Program, Faculty of Medicine, Universitas Hasanuddin, Makassar, South Sulawesi, Indonesia. https://orcid.org/0009-0004-0215-2371
  • Farida Tabri Department of Dermatology and Venereology Faculty of Medicine Universitas Hasanuddin, Makassar, Indonesia.
  • Sri Vitayani Muchtar Department of Dermatology and Venereology Faculty of Medicine Universitas Muslim, Makassar, Indonesia.
  • Mochammad Hatta Department of Molecular Biology and Immunology, Faculty of Medicine Universitas Hasanuddin, Makassar, Indonesia.
  • Khaeruddin Djawad Department of Dermatology and Venereology, Faculty of Medicine Universitas Muhammadiyah, Makassar, Indonesia.
  • Farida Ilyas Department of Dermatology and Venereology Faculty of Medicine Universitas Hasanuddin, Makassar, Indonesia.
  • Sitti Musafirah Department of Dermatology and Venereology, Faculty of Medicine Universitas Muhammadiyah, Makassar, Indonesia.
  • Muhammad Nasrum Massi Department of Microbiology, Faculty of Medicine Universitas Hasanuddin, Makassar, Indonesia.
  • Agussalim Bukhari Department of Clinical Nutrition, Faculty of Medicine Universitas Hasanuddin, Makassar, Indonesia.
  • Andi Alfian Zainuddin Department of Public Health, Faculty of Medicine Universitas Hasanuddin, Makassar, Indonesia.

Erythema nodosum leprosum (ENL) is an immunological complication of leprosy characterized by acute inflammation of the skin, nerves, and other organs. Identifying laboratory parameters is important for early diagnosis of leprosy reactions. Various cytokine biomarkers have been examined and only a few studies have reported on angiogenesis in leprosy. This study aims to understand the pathomechanism of ENL by examining IL-7 and plateletderived growth factor (PDGF)-BB mRNA expression that can be the development and consideration of new effective therapies to prevent reactions, recurrences, and defects in leprosy. The study used a cross-sectional analytic design. Sampling was done by peripheral blood from the patient and measuring mRNA expression with specific primers RT-PCR. The expression of mRNA IL-7 and PDGF-BB was significantly different between multibasilar patients without reaction and with ENL reaction, where there was an increased expression in ENL patients. This could be used as the development of potential biomarkers in ENL and development of new therapeutic intervention pathways in ENL.


Hungria EM, Sekula SB, Oliviera RMD, Aderaldo LC, Pontes ADet al. Leprosy reactions: The predictive value of mycobacterium leprae-specific serology evaluated in a Brazilian cohort of leproy reactions (U-MDT/CT-BR). Plos Neglected Tropical Diseases.2017.11(2).

WHO. Global leprosy (Hansen disease) update,2019.Time to step-up prevention initiatives.Wkly. Epidermiol.Rec.2020;95:417-440

Pandhi D, Chhabra N. New insights in the pathogenesis of type 1 and type 2 lepra reaction. Indian J Dermatol Venereol Leprol. 2013; 79(6):739–49 DOI: https://doi.org/10.4103/0378-6323.120719

Kumar B, Kar K.M. Text book of Leprosy. Indian Association of Leprologists. The

Health Science Publisher. India. 2010. 424-431

Bilik L, Demir B, Cicek D. Leprosy reactions. Intech open. Turki: 2017:81-91

Polycarpou A, Walker SL, Lockwood DN. A systematic review of immunological studies of erythema nodosum leprosum. Front Immunol. 2017;8:233 DOI: https://doi.org/10.3389/fimmu.2017.00233

Iyer A, Hatta M, Usman R, Luiten S, Oskam L et al. Serum leve;s of interferon , tumour necrosis factor-,soluble interleukin-6R and soluble cell activation markers for monitoring response to treatment of leprosy reactions. Clinical and Experimental Immunology. 2007;150;210-16 DOI: https://doi.org/10.1111/j.1365-2249.2007.03485.x

Rusyati LM, Hatta M, Widiana IG, Adiguna MS, Wardana M et al. Higher Treg FoxP3 and TGF- mRNA exprsesion in type 2 reaction ENL (Erythema Nodosum Leprosum) Patients in Mycobacterium leprae infection. The open MicrobiologyJournal. 2020:14:304-9 DOI: https://doi.org/10.2174/1874434602014010304

Stefani MM, Guerra JG, Sousa ALM, Costa MB, Oliveira ML, et.al. Potential plasma markers of type 1 and 2 leprosy reactions: a preliminary report. Brazil: BMC Infectious Diseases. 2009;9:75 DOI: https://doi.org/10.1186/1471-2334-9-75

Bikker A, Hack CE, Lafeber FPJG, Roon JAG. Interleukin-7 : a key mediator in T cell-driven autoimmunity. Current Pharmaceutical Design. 2012;18:1-10 DOI: https://doi.org/10.2174/138161212800165979

Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. 2008. Genes & Development. 22:1276–1312 DOI: https://doi.org/10.1101/gad.1653708

Fretto LJ, Snape AJ, Tomlinson JE, Seroogy JJ, Wolf DL, et.al. Mechanism of platelet-derived growth factor AA, AB, and BB binding to α and β PDGF receptor. The journal of biological chemistry. 1993;268(5):3625-31 DOI: https://doi.org/10.1016/S0021-9258(18)53739-X

Antunes SL, Motta E, de Almeida SM, Gallo ME, Nery JA, Lenzi HL. Distinct patterns of microvasculature in the cutaneous lesions of leprosy. Int J Lepr Other Mycobact Dis. 2000;68:143–151

Vilani-Moreno FR, Brito-de-Souza VN, Silva SUR, Barbosa AS, Sartori BG, Campanelli AP, et al. Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker. Indian J Dermatol Venereol Leprol 2021;87:190-8. DOI: https://doi.org/10.25259/IJDVL_143_20

PocaterraL,JainS,ReddyR,MuzaffarullahS,TorresO,SuneethaS,etal.Clinical course of erythema nodosum leprosum: An 11-year cohort study in Hyderabad, India. The American Journal of Tropical Medicine and Hygiene. 2006;74:868-879 DOI: https://doi.org/10.4269/ajtmh.2006.74.868

Arora M, Katoch K, Natrajan M, Kamal R, Yadav VS. Changing profile of disease in leprosy patients diagnosed in a tertiary care centre during years 1995‐2000.Indian J Lepr. 2008.;80 :257‐65

Iyer A,Eijk M, Silva E, Hatta M, Faver W, Aerts JM et al. Increased chitotriosidase activity in serum of leprosy patients : Association with bacillary leprosy. Clinical Immunology.2009;131:501-9 DOI: https://doi.org/10.1016/j.clim.2009.02.003

Barnes PF, Chatterjee D, Brennan PJ, Rea TH, Modlin RL. Tumor necrosis factor production in patients with leprosy. Infection and immunity. 1992;60(4):1441-1446. DOI: https://doi.org/10.1128/iai.60.4.1441-1446.1992

Belgaumkar VA, Gokhale NR, Mahajan PM, Bharadwaj R, Pandit DP, Deshpande S. Circulating cytokine profiles in leprosy patients. Lepr Rev 2007;78:223‐30. DOI: https://doi.org/10.47276/lr.78.3.223

Appasamy PM. Biological and clinical implications of interleukin-7 and lymphopoiesis. Cytokines Cell Mol Ther 1999;5:25–39.

Lundstrom W, Fewkes NM, Mackall CL. IL-7 in human health and disease. Immunol. 2012;24:218–24. DOI: https://doi.org/10.1016/j.smim.2012.02.005

Alpdogan O, van den Brink MR. IL-7 and IL-15 : Therapeutic Cytokines for Immunodeficiency. Trends Immunol (2005) 26(1):56–64 DOI: https://doi.org/10.1016/j.it.2004.11.002

Gonzalez-Quintial R, Lawson BR, Scatizzi JC, Craft J, Kono DH, Baccala R, et al. Systemic autoimmunity and lymphoproliferation are associated with excess IL-7 and inhibit byIL-7Rα blockade. PLoS One. 2011;6:e27528. DOI: https://doi.org/10.1371/journal.pone.0027528

Roon JA, Glaudem KA, Bijlsma JW, Lafeber FP. Interleukin 7 stimulates tumor necrosis factor α and Th1 cytokine production in joints of patients with rheumatoid arthritis. Ann Rheum Dis 2003;62:113–119 DOI: https://doi.org/10.1136/ard.62.2.113

Chen D, Tang T-X, Deng H, Yang X-P and Interleukin-7 Biology and Its Effects on Immune Cells: Mediator of Generation, Differentiation, Survival, and Homeostasis. Front. Immunol.2021;12:747324 DOI: https://doi.org/10.3389/fimmu.2021.747324

Martin F, Chan AC. B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol. 2006;23(24):467-496. DOI: https://doi.org/10.1146/annurev.immunol.24.021605.090517

Kifayet A, Shahid F, Lucas S, Hussain R. Erythema nodosum leprosum is associated with upregulation of polyclonal IgG1 antibody synthesis. Clin Exp Immunol 1996;106:44753. DOI: https://doi.org/10.1046/j.1365-2249.1996.d01-860.x

Huggenberger R, Detmar M. The cutaneous vascular system in chronic skin inflammation. The predictive value of mycobacterium leprae-specific serology evaluated in a Brazilian cohort of leprosy patients ( U-MDT/CT-BR). Plos Neglected Tropical Diseases. 2017. 11(2) DOI: https://doi.org/10.1371/journal.pntd.0005396

Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438 : 932-936 DOI: https://doi.org/10.1038/nature04478

El-Khawalany M, Shaaban D, Sultan M, Alsalam FA. Inhibition of angiogenesis as a new therapeutic target in the treatment of lepromatous leprosy. Clinical, Cosmetic and Investigational Dermatology. 2012:5 1–6 DOI: https://doi.org/10.2147/CCID.S26200

Kadarsih Banjar, F., Tabri, F., Muchtar, S. V., Hatta, M., Djawad, K., Ilyas, F., Musafirah, S., Massi, M. N., Bukhari, A., & Zainuddin, A. A. (2023). Analysis of interleukin 7 and platelet-derived growth factor-BB mRNA expression as potential markers in erythema nodosum leprosum. Dermatology Reports, 16(1). https://doi.org/10.4081/dr.2023.9773

Downloads

Download data is not yet available.

Citations