Down-regulated Th17 cells in a patient with familial Mediterranean fever associated with amyloid A amyloidosis in the treatment of canakinumab.

Abstract

Autoinflammatory diseases are innate immune-mediated inflammatory disorders, unlike autoimmune diseases, which are characterised by abnormalities in adoptive immunity, although autoimmune and autoinflammatory diseases have certain similar clinical features. Familial Mediterranean fever (FMF), the most common monogenic autoinflammatory disease, is associated with mutations in the MEFV gene that encodes pyrin, which results in inflammasome activation and uncontrolled production of interleukin (IL)-1β. Regular use of colchicine, the primary drug for FMF treatment, prevents febrile attacks and reduces the long-term risk of subsequent complications of amyloid A (AA) amyloidosis. However, a minority of FMF patients develop colchicine resistance, and anti-IL-1β treatment with canakinumab, which is a genetically modified human IgG subclass type 1 (IgG1) monoclonal antibody specific for human IL-1β, was beneficial in inhibiting inflammation in such patients. Here, we present a patient with FMF associated with AA amyloidosis, who was treated with canakinumab and demonstrated down-regulated Th17 cells and activated Th17 cells (from 21.4% to 12.8%, and from 1.45% to 0.83%, respectively) in peripheral blood, as shown by immunophenotyping via multicolour flow cytometry and by disease activity and improved laboratory inflammatory surrogate markers-C-reactive protein (CRP) and serum AA protein (SAA). CRP had values within normal limits, but SAA did not (Spearman's rank correlation coefficient; ρ = 0.133). We report that SAA and IL-1β may differentiate Th17 cells from CD4+-naïve T cells, and we discuss interactions between autoinflammation and autoimmunity as a model based on this case, through modes of action with IL-1β and SAA. This report is the first demonstrating that an IL-1β antagonist may reduce Th17 cells in FMF as a therapeutic option.

• Authors: Takeshi Goto, Yusuke Miyazaki, Shingo Nakayamada, Naoki Shiraishi, Takeshi Yoshinaga, Yoshiya Tanaka, Tadashi Nakamura
• Journal: Modern rheumatology case reports (Mod Rheumatol Case Rep) Vol. 7 Issue 1 Pg. 237-242 (01 03 2023) ISSN: 2472-5625 [Electronic] England
• PMID: 35349715 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• canakinumab
• Interleukin 1 Receptor Antagonist Protein
• Colchicine
• MEFV protein, human
• Pyrin

Topics

• Humans
• Familial Mediterranean Fever (complications, diagnosis, drug therapy)
• Th17 Cells
• Interleukin 1 Receptor Antagonist Protein (therapeutic use)
• Colchicine (therapeutic use)
• Pyrin