Cytokine and chemokine multiplex analysis-based exploration for potential treatment and prognostic prediction in large-vessel vasculitis: A preliminary observational study

被引：3

作者：

Abe, Nobuya ^{[1
,2
,3
]}

Kono, Michihiro ^{[1
,2
]}

Kono, Michihito ^{[1
,2
]}

Katsuyama, Takayuki ^{[4
]}

Ohmura, Kazumasa ^{[1
,2
]}

Sato, Taiki ^{[1
,2
]}

Karino, Kohei ^{[1
,2
]}

Fujieda, Yuichiro ^{[1
,2
]}

Kato, Masaru ^{[1
,2
]}

Hasebe, Rie ^{[5
]}

Murakami, Masaaki ^{[3
]}

Atsumi, Tatsuya ^{[1
,2
]}

机构：

[1] Hokkaido Univ, Fac Med, Dept Rheumatol Endocrinol & Nephrol, Sapporo, Japan

[2] Hokkaido Univ, Grad Sch Med, Sapporo, Japan

[3] Hokkaido Univ, Inst Genet Med, Grad Sch Med, Div Mol Psychoimmunol, Sapporo, Japan

[4] Okayama Univ, Grad Sch Med, Dept Nephrol Rheumatol Endocrinol & Metab, Okayama, Japan

[5] Hokkaido Univ, Inst Genet Med, Ctr Infect Canc, Sapporo, Japan

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

关键词：

large vessel vasculitis; Takayasu arteritis; giant cell arteritis; proteomics; cytokine; chemokine; clustering; Janus-kinase inhibitor; GIANT-CELL ARTERITIS; TAKAYASU ARTERITIS; TH17;

D O I：

10.3389/fimmu.2022.1066916

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Large-vessel vasculitis (LVV) is subclassified into two phenotypes; Takayasu arteritis and giant cell arteritis. Although the pathogenesis of LVV is not fully established, IL-6-IL-17 axis and IL-12-IFN-gamma axis play critical roles in the disease development. We aimed to clarify the association between the disease state and cytokine/chemokine levels, to assess disease course as prognosis and to predict regulators in patients with LVV using the blood profiles of multiple cytokines/chemokines. This retrospective analysis comprised 35 LVV patients whose blood were collected, and multiplex cytokine/chemokine analysis with 28 analytes was performed. The differences of cytokines/chemokines corresponding disease status, upstream regulator analysis, pathway analysis and cluster analysis were conducted using the cytokines/chemokines profile. Relapse-free survival rate was calculated with Kaplan-Meier analysis in the classified clusters. In the robust analysis, IL-4, CCL2/MCP-1, TNFSF13/APRIL, TNFSF13B/BAFF, CHI3L1 and VEGF-A levels were significantly changed after treatment. Untreated LVV patients demonstrated activation of NF kappa B-related molecules and these patients are potentially treated with JAK/STAT inhibitors, anti-TNF-alpha inhibitors and IL-6 inhibitors. Cluster analysis in active LVV patients revealed two clusters including one with high blood levels of IL-1 beta, IL-6, IL-17, IL-23 and CCL20/MIP-3. A subgroup of the LVV patients showed activated IL-17 signature with high relapse frequency, and JAK/TyK2 inhibitors and IFN-gamma inhibitors were detected as potentially upstream inhibitors. Blood cytokine/chemokine profiles would be useful for prediction of relapse and potentially contributes to establish therapeutic strategy as precision medicine in LVV patients.

引用

页数：7