Altered B cell phenotype and CD27+memory B cells are associated with clinical features and environmental exposure in Colombian systemic lupus erythematosus patients

• Type of Material: Article
• Authors: Carolina Hurtado, Universidad CES, Medellín; Diego Fernando Rojas-Gualdron, Universidad CES, Medellín; Rodrigo Urrego, Universidad CES, Medellín; Kevin Cashman, Emory University; Elsa Maria Vasquez-Trespalacios, Universidad CES, Medellín; Juan Camilo Diaz-Coronado, Universidad CES, Medellín; Mauricio Rojas, Universidad de Antioquia, Medellín; Scott Jenks, Emory University; Gloria Vásquez, Universidad de Antioquia, Medellín; Ignacio Sanz, Emory University
• Language: English
• Date: 2022-09-06
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Hurtado, Rojas-Gualdrón, Urrego, Cashman, Vásquez-Trespalacios, Díaz-Coronado, Rojas, Jenks, Vásquez and Sanz.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fmed.2022.950452
• Title of Journal or Parent Work: FRONTIERS IN MEDICINE
• Volume: 9
• Start Page: 950452
• End Page: 950452
• Grant/Funding Information: This work was also supported by the Research and Innovation Department of CES University (grant code INV.032017.006) and the Colombian Association of Immunology (ACOI).; This study was supported by the Lowance Center for Human Immunology, Emory University, and the Emory University School of Medicine Flow Cytometry Core.
• Keywords: METHYLATION; IFI44L; B lymphocytes; DISEASE-ACTIVITY; EXPRESSION; Medicine, General & Internal; SUBSETS; lupus nephritis; MRL; TRICHLOROETHYLENE; Science & Technology; AUTOREACTIVITY; General & Internal Medicine; occupational exposure; Life Sciences & Biomedicine; solvents; autoimmunity; systemic lupus erythematosus; IGD
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background: B lymphocytes are dysregulated in Systemic Lupus Erythematosus (SLE) including the expansion of extrafollicular B cells in patients with SLE of African American ancestry, which is associated with disease activity and nephritis. The population of Colombia has a mixture of European, Native American, and African ancestry. It is not known if Colombian patients have the same B cell distributions described previously and if they are associated with disease activity, clinical manifestations, and environmental exposures. Objective: To characterize B cell phenotype in a group of Colombian Systemic Lupus Erythematosus patients with mixed ancestry and determine possible associations with disease activity, clinical manifestations, the DNA methylation status of the IFI44L gene and environmental exposures. Materials and methods: Forty SLE patients and 17 healthy controls were recruited. Cryopreserved peripheral B lymphocytes were analyzed by multiparameter flow cytometry, and the DNA methylation status of the gene IFI44L was evaluated in resting Naive B cells (rNAV). Results: Extrafollicular active Naive (aNAV) and Double Negative type 2, DN2 (CD27− IgD− CD21− CD11c+) B cells were expanded in severe active patients and were associated with nephritis. Patients had hypomethylation of the IFI44L gene in rNAV cells. Regarding environmental exposure, patients occupationally exposed to organic solvents had increased memory CD27+ cells (SWM). Conclusion: aNAV and DN2 extrafollicular cells showed significant clinical associations in Colombian SLE patients, suggesting a relevant role in the disease’s pathophysiology. Hypomethylation of the IFI44L gene in resting Naive B cells suggests that epigenetic changes are established at exceedingly early stages of B cell ontogeny. Also, an alteration in SWM memory cells was observed for the first time in patients exposed to organic solvents. This opens different clinical and basic research possibilities to corroborate these findings and deepen the knowledge of the relationship between environmental exposure and SLE.