Peripheral T cell populations are differentially affected in monogenic autoinflammatory syndromes and gout

Abstract

Purpose Both monogenic autoinflammatory syndromes, such as Chronic Granulomatous Disease (CGD) and Familial Mediterranean Fever (FMF), and the common inflammatory disease gout are characterized by episodes of sterile inflammatory attacks in the absence of an infection. While these disorders encompass distinct pathologies due to differentially affected metabolic pathways and inflammasome activation mechanisms, their common features are the excessive production of interleukin (IL)-1ß and innate immune cell hyperreactivity. On the other hand, the role of T cells and innate-like lymphocytes such as gamma delta (γδ) T cells in these pathologies is ill-defined. Methods In order to widen our understanding of T cell involvement in FMF, CGD and gout pathology we developed multicolour immunophenotyping panels for flow cytometry and functional assays to characterise gd T cells, as well as CD4 and CD8 T cell populations in terms of their cytokine production, activation status, memory or naive phenotypes, exhaustion status, homing receptor expression, and cytotoxic activity. Results Our study is the first deep immunophenotyping analysis of T cell populations in FMF, CGD and gout patients. We found that CGD affects the frequencies and activation status of T cells, while gout impairs cytokine production capacity of Vd2 T cells and reshapes homing receptor expression by T cells. FMF was characterized by only minor effects on T cell populations. Conclusion Autoinflammatory syndromes differentially affect T cell compartments. Future studies are warranted to assess whether these phenotypical changes are relevant for disease pathology.