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

哥伦比亚系统性红斑狼疮患者的 B 细胞表型改变和 CD27+ 记忆 B 细胞与临床特征和环境暴露相关

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作者:Carolina Hurtado, Diego Fernando Rojas-Gualdrón, Rodrigo Urrego, Kevin Cashman, Elsa María Vásquez-Trespalacios, Juan Camilo Díaz-Coronado, Mauricio Rojas, Scott Jenks, Gloria Vásquez, Ignacio Sanz

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.

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.

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).

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

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).

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