Dysregulated mature IL-1β production in familial Mediterranean fever

被引：15

作者：

Migita, Kiyoshi ^{[1
,2
]}

Izumi, Yasumori ^{[1
,2
]}

Fujikawa, Keita ^{[3
]}

Agematsu, Kazunaga ^{[4
]}

Masumoto, Junya ^{[5
,6
]}

Jiuchi, Yuka ^{[1
,2
]}

Kozuru, Hideko ^{[1
,2
]}

Nonaka, Fumiaki ^{[7
]}

Shimizu, Toshimasa ^{[7
]}

Nakamura, Tadashi ^{[8
]}

Iwanaga, Nozomi ^{[1
,2
]}

Furukawa, Hiroshi ^{[9
]}

Yasunami, Michio ^{[10
]}

Kawakami, Atsushi ^{[11
]}

Eguchi, Katsumi ^{[7
]}

机构：

[1] Nagasaki Med Ctr, Dept Rheumatol, Omura, Japan

[2] Nagasaki Med Ctr, Clin Res Ctr, Omura, Japan

[3] Isahaya Hlth Insurance Gen Hosp, Dept Rheumatol, Nagasaki, Japan

[4] Shinshu Univ, Grad Sch Med, Dept Infect & Host Def, Matsumoto, Nagano 390, Japan

[5] Ehime Univ, Grad Sch Med, Dept Pathol, Matsuyama, Ehime 790, Japan

[6] Proteosci Ctr, Matsuyama, Ehime, Japan

[7] Sasebo City Gen Hosp, Dept Rheumatol, Sasebo, Japan

[8] Shinto Kumamoto Hosp, Dept Rheumatol, Kumamoto, Japan

[9] Natl Hosp Org, Sagamihara Natl Hosp, Clin Res Ctr, Sagamihara, Kanagawa, Japan

[10] Nagasaki Univ, Inst Trop Med NEKKEN, Nagasaki 852, Japan

[11] Nagasaki Univ Hosp, Dept Rheumatol, Nagasaki, Japan

来源：

RHEUMATOLOGY | 2015年 / 54卷 / 04期

关键词：

IL-1; beta; familial Mediterranean fever; biomarker; autoinflammatory disease; serum amyloid A; PYRIN; INTERLEUKIN-1-BETA; PROTEIN; ACTIVATION; CASPASE-1; MUTATIONS; INTERACTS; DISEASES; BINDING; DOMAIN;

D O I：

10.1093/rheumatology/keu359

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective. The aim of this study was to analyse the role of circulating cleaved IL-1 beta in patients with FMF. Methods. We enrolled 20 patients with FMF (5 males and 15 females), 22 patients with RA (4 males and 18 females) and 22 healthy controls (6 males and 16 females). Serum levels of serum amyloid A (SAA) were measured by ELISA. We also determined whether IL-1 beta was present as the cleaved form (p17) in the sera of FMF patients by immunoblotting using anti-cleaved IL-1 beta antibody. Results. Although SAA concentrations were elevated in the sera, there was no significant difference in these concentrations between FMF patients and RA patients. Immunoblot analysis demonstrated that the cleaved form of IL-1 beta (p17) was present in sera from FMF patients during febrile attack periods, but not in healthy controls. Bands representing the cleaved form of IL-1 beta were not detected in serum from FMF patients at non-febrile attack periods or remission periods under colchicine treatment. The amounts of cleaved IL-1 beta (p17) were significantly higher in patients with FMF compared with those in patients with RA in the inflammatory phase. Conclusion. The cleaved form of IL-1 beta is a valuable biomarker for monitoring disease activity and response to colchicine treatment in patients with FMF. It might be useful to discriminate FMF from other non-IL-1 beta-mediated inflammatory disorders.

引用

页码：660 / 665

页数：6

共 19 条

[1] Microarray-based identification of novel biomarkers in IL-1-mediated diseases [J].

Allantaz, Florence ;

Chaussabel, Damien ;

Banchereau, Jacques ;

Pascual, Virginia .

CURRENT OPINION IN IMMUNOLOGY, 2007, 19 (06) :623-632

[2] Chronic inflammation in FmF: markers, risk factors, outcomes and therapy [J].

Ben-Zvi, Ilan ;

Livneh, Avi .

NATURE REVIEWS RHEUMATOLOGY, 2011, 7 (02) :105-112

[3]

BORTH W, 1990, BLOOD, V75, P2388

[4]

BORTH W, 1990, J IMMUNOL, V145, P3747

[5] Advances in the understanding of familial Mediterranean fever and possibilities for targeted therapy [J].

Chae, Jae J. ;

Aksentijevich, Ivona ;

Kastner, Daniel L. .

BRITISH JOURNAL OF HAEMATOLOGY, 2009, 146 (05) :467-478

[6] The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-κB through its N-terminal fragment [J].

Chae, Jae Jin ;

Wood, Geryl ;

Richard, Katharina ;

Jaffe, Howard ;

Colburn, Nona T. ;

Masters, Seth L. ;

Gumucio, Deborah L. ;

Shoham, Nitza G. ;

Kastner, Daniel L. .

BLOOD, 2008, 112 (05) :1794-1803

[7] The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1β production [J].

Chae, Jae Jin ;

Wood, Geryl ;

Masters, Seth L. ;

Richard, Katharina ;

Park, Grace ;

Smith, Brian J. ;

Kastner, Daniel L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (26) :9982-9987

[8] Gain-of-Function Pyrin Mutations Induce NLRP3 Protein-Independent Interleukin-1β Activation and Severe Autoinflammation in Mice [J].

Chae, Jae Jin ;

Cho, Young-Hun ;

Lee, Geun-Shik ;

Cheng, Jun ;

Liu, P. Paul ;

Feigenbaum, Lionel ;

Katz, Stephen I. ;

Kastner, Daniel L. .

IMMUNITY, 2011, 34 (05) :755-768

[9] Biologic basis for interleukin-1 in disease [J].

Dinarello, CA .

BLOOD, 1996, 87 (06) :2095-2147

[10] Blocking IL-1 in systemic inflammation [J].

Dinarello, CA .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (09) :1355-1359

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