Multiple Serum Cytokine Profiling to Identify Specific Molecular Networks in Attacks of Familial Mediterranean Fever

Tomohiro Koga¹, Kiyoshi Migita², Shuntaro Sato³, Masataka Umeda⁴, Shoichi Fukui⁵, Ayako Nishino⁴, Shinya Kawashiri⁶, Naoki Iwamoto⁵, Kunihiro Ichinose⁵, Mami Tamai⁵, Hideki Nakamura⁵, Tomoki Origuchi⁷, Yukitaka Ueki⁸, Kazunaga Agematsu⁹, Katsumi Eguchi¹⁰ and Atsushi Kawakami⁴, ¹Departments of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ²Department of Rheumatology and Clinical Research Center, Nagasaki Medical Center, Omura, Japan, ³Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan, ⁴Department of Immunology and Rheumatology, Nagasaki University, Nagasaki, Japan, ⁵Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁶Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁷Department of Rehabilitation Sciences, Nagasaki University, Nagasaki, Japan, ⁸Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Sasebo, Japan, ⁹Department of Infectious Immunology, Shinshu University, Graduate School of Medicine, Shinshu, Japan, ¹⁰Department of Rheumatology, Sasebo Chuo Hospital, Sasebo, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Autoinflammation, cytokines and familial Mediterranean fever, IL-1/IL-18, IL-6

Session Information

Date: Sunday, November 8, 2015

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:
Familial mediterranean fever (FMF) is caused by a number of mutations of the MEFV gene, coding for a protein named pyrin that acts as a major regulatory component of the inflammasome. It
is widely accepted that elevated acute phase proteins such as SAA, CRP and
inflammatory cytokines including IL-6, IL-18 are found in active phase of patients
with FMF. However serum cytokine profiling of FMF patients still remains to be
obscure. The aim of this study was to identify the utility of multiple
cytokines measurement for understanding the specific molecular networks in
patients with FMF.

Methods: FMF patients in attack or remission were classified
by Japan College of Rheumatology-certified rheumatologists through medical
records. Serum levels of 45 cytokines were measured by multi-suspension
cytokine array from 49 FMF patients, in either attack or remission, and 33
age-matched controls. They gave their informed consent to be subjected to the
protocol, which was approved by the Institutional Review Board of Nagasaki
University. Multivariate classification algorithms were used to determine
discriminating biomarkers.

Results: Twenty-nine out of 45 cytokines were available for further analyses. Serum
levels of 8 cytokines (IL-4, IL-6, IL-7, IL-17, IL-18, G-CSF, ICAM-1 and
CXCL10) were significantly elevated from FMF in attack than healthy control.
Furthermore, eleven cytokines (IL-6, IL-10, IL-12p40, IL-12p70, IFN-alpha,
IFN-gamma, GM-CSF, G-CSF, FGF-2, CXCL10 and CX3CL1) were increased from FMF in
attack compared to FMF in remission. We performed multivariate classification algorithm and ranked
cytokines by their importance (Fig. 1) and found that IL-6, sICAM-1, IL-18 and
IL-17 were the best combination to distinguish FMF in attack from healthy
control with high accuracy (sensitivity; 92.0%, specificity; 93.9%, accuracy;
93.1%). Among FMF patients, combined measurement of IL-6, G-CSF IL-10 and
IL-12p40 discriminated FMF in attack from FMF in remission with high accuracy
(sensitivity; 76%, specificity; 90.3%, accuracy; 83.9%).

Conclusion: Our data suggest for the first time that specific molecular
interactions are present in patients with FMF based on multiple cytokines
measurement. These findings may extend to our further understanding of the
activation of inflammasome leading to promote
cytokine networks.

Disclosure: T. Koga, None; K. Migita, None; S. Sato, None; M. Umeda, None; S. Fukui, None; A. Nishino, None; S. Kawashiri, None; N. Iwamoto, None; K. Ichinose, None; M. Tamai, None; H. Nakamura, None; T. Origuchi, None; Y. Ueki, None; K. Agematsu, None; K. Eguchi, None; A. Kawakami, None.

To cite this abstract in AMA style:

Koga T, Migita K, Sato S, Umeda M, Fukui S, Nishino A, Kawashiri S, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Ueki Y, Agematsu K, Eguchi K, Kawakami A. Multiple Serum Cytokine Profiling to Identify Specific Molecular Networks in Attacks of Familial Mediterranean Fever [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/multiple-serum-cytokine-profiling-to-identify-specific-molecular-networks-in-attacks-of-familial-mediterranean-fever/. Accessed .

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