Immunohistochemical evaluation of protein expression of hyperexpressed genes (ADAMTS4, FAM26F, IL1B, KRT6C, MMP9, MT2A, NNMT, PTX3 and UBD) in leprosy forms and reactions

• Grant number: 20/01365-6
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2020
• End date: July 31, 2023
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Cléverson Teixeira Soares
• Grantee: Cléverson Teixeira Soares
• Host Institution: Instituto Lauro de Souza Lima (ILSL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). Bauru , SP, Brazil
• Associated researchers: Ana Paula Favaro Trombone Garlet ; Andrea de Faria Fernandes Belone ; Luciana Raquel Vincenzi Fachin ; Patrícia Sammarco Rosa

Abstract

Leprosy is a chronic infectious disease whose etiological agent is Mycobacterium leprae. In Brazil, around 30,000 new cases of leprosy are reported every year. It is a complex disease in different aspects (clinical, histopathological and molecular) and a major public health problem in Brazil. Despite having effective treatment through multidrug therapy (MDT), unfortunately many patients, during the course of the disease or after treatment, develop reaction phenomena. These phenomena, known as type 1 (R1) reaction and type 2 (R2 or leprosy erythema nodosum and its variants), further aggravate the neuromuscular problems of leprosy patients, which can cause severe and permanent sequelae. There is no effective treatment for leprosy reactions or serological markers that can predict their onset or even identify them. For R1 corticosteroids are commonly prescribed and for R2 preferably thalidomide. Both medications may cause undesirable teratogenic or side effects. The pathophysiological mechanisms that trigger leprosy reaction phenomena are unknown. Clarifying them is crucial for understanding the pathophysiology of reactions and also for the discovery of new targets that serve to prevent or treat leprosy reactions more effectively and specifically. In this project, we propose to evaluate the protein expression of some genes that were identified by us in a previous study funded by FAPESP (Process No. 2010 / 19286-3). They are differentially overexpressed genes mainly in samples of leprosy R1 and R2 (ADAMTS4, FAM26F, IL1B, KRT6C, MMP9, MT2A, NNMT, PTX3 and UBD). Our hypothesis is that the characterization of protein expression by immunohistochemistry of these genes in skin samples may contribute to the knowledge of these reaction phenomena, allowing: (1) to identify the protein expression of genes in the different cell types that make up the infiltrates involved throughout the leprosy spectrum and its reaction frameworks; (2) increase understanding of the pathophysiology of reactions (R1 and R2); (3) identify biomarkers that may serve as possible markers of reaction phenomena; and (4) the discovery of new therapeutic targets that can be used for the prevention and / or treatment of leprosy reactions. (AU)