sTREM-1 and TNF-α levels are associated with the clinical outcome of leprosy patients

Márcio Bezerra-Santos; Lays G Santos Bomfim; Camilla N Oliveira Santos; Maria Wiliane N Cunha; Eduardo J Rocha de Moraes; Rodrigo A Cazzaniga; Martha D L Tenório; Jonnia M Sherlock Araujo; Lucas Menezes-Silva; Lucas Sousa Magalhães; Aline S Barreto; Steven G Reed; Malcolm S Duthie; Michael W Lipscomb; Roque Pacheco de Almeida; Tatiana Rodrigues de Moura; Amélia Ribeiro de Jesus

doi:10.3389/fmed.2023.1177375

sTREM-1 and TNF-α levels are associated with the clinical outcome of leprosy patients

Front Med (Lausanne). 2023 Jun 29:10:1177375. doi: 10.3389/fmed.2023.1177375. eCollection 2023.

Authors

Márcio Bezerra-Santos^{1

2

3}, Lays G Santos Bomfim^{2

3}, Camilla N Oliveira Santos^{2

3}, Maria Wiliane N Cunha², Eduardo J Rocha de Moraes², Rodrigo A Cazzaniga^{2

3}, Martha D L Tenório^{3

4}, Jonnia M Sherlock Araujo^{3

4}, Lucas Menezes-Silva², Lucas Sousa Magalhães^{2

3}, Aline S Barreto^{2

3}, Steven G Reed⁵, Malcolm S Duthie⁵, Michael W Lipscomb⁶, Roque Pacheco de Almeida^{2

3

7

8}, Tatiana Rodrigues de Moura^{2

3}, Amélia Ribeiro de Jesus^{2

3

7

8}

Affiliations

¹ Centro de Ciências Médicas e Enfermagem, Universidade Federal de Alagoas, Maceió, Brazil.
² Laboratório de Imunologia e Biologia Molecular, Universidade Federal de Sergipe, Aracaju, Brazil.
³ Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Sergipe, Aracaju, Brazil.
⁴ Departamento de Dermatologia, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
⁵ Host Directed Therapeutics (HDT) Bio Corp, Seattle, WA, United States.
⁶ Department of Pharmacology, University of Minnesota, Minneapolis, MN, United States.
⁷ Departamento de Medicina, Universidade Federal de Sergipe, Aracaju, Brazil.
⁸ Instituto de Investigação em Imunologia (III), Institutos Nacionais de Ciência e Tecnologia (INCTs), Conselho Nacional de Pesquisa e Tecnologia (CNPq), São Paulo, Brazil.

Abstract

Leprosy reaction (LR) and physical disability (PD) are the most significant clinical complications of leprosy. Herein, we assessed the circulating serum-sTREM-1 and TNF-α levels and their genetic polymorphisms in leprosy. Serum-sTREM-1 and TNF-α levels were measured in leprosy patients (LP) before treatment (n = 51) and from their household contacts (HHCs; n = 25). DNA samples were genotyped using TREM-1 rs2234246 and TNF-α rs1800629-SNP in 210 LPs and 168 endemic controls. The circulating sTREM-1 and TNF-α levels are higher in the multibacillary form. The ROC curve of the serum-sTREM-1 levels was able to differentiate LR from non-LR and PD from non-PD. Similarly, LPs with serum-sTREM-1 levels >210 pg/ml have 3-fold and 6-fold higher chances of presenting with LR and PD, respectively. Genotypes CC+CT of the TREM-1 were associated with leprosy. Taken together, our analyses indicated that sTREM-1 and TNF-α play an important role in the pathogenesis of leprosy and provide promising biomarkers to assist in the diagnosis of leprosy complications.

Keywords: immune markers; inflammatory cytokine; leprosy; leprosy complications; soluble TREM-1.

Grants and funding

This study was supported by Grants MCTIC/CNPq N 28/2018, Process: 421060/2018-2 and CHAMADA MS/CNPq/FAPITEC/SE/SES N° 06/2018–PPSUS SERGIPE 2017/2018. EDITAL CAPES/FAPITEC N° 11/2016–PROEF [Grant Number 88881.157436/2017-01]. RC and LM are postdocs supported by CAPES and CNPq, respectively. CS, MC, and AB have fellowships supported by CAPES and CNPq. AJ, RA, and TM are scientists supported by CNPQ.