Characterization of NLRP3 Variants in Japanese Cryopyrin-Associated Periodic Syndrome Patients (original) (raw)

Abstract

The etiology of cryopyrin-associated periodic syndrome (CAPS) is caused by germline gene mutations in NOD-like receptor family, pryin domain containing 3 (NLRP3)/cold-induced autoinflammatory syndrome 1 (CIAS1). CAPS includes diseases with various severities. The aim of this study was to characterize patients according to the disease severity of CAPS. Five Japanese patients with four kinds of gene variations in NLRP3 were found and diagnosed as CAPS or juvenile idiopathic arthritis. Two mutations in NLRP3, Y563N and E688K, found in CAPS patients exhibit significant positive activities in the nuclear factor-κB reporter gene assay. Increased serum interleukin (IL)-18 levels were only observed in severe cases of CAPS. In mild cases of CAPS, the serum IL-18 levels were not increased, although lipopolysaccharide- or hypothermia-enhanced IL-1β and IL-18 production levels by their peripheral blood mononuclear cells were detectable. This series of case reports suggests that a combination of in vitro assays could be a useful tool for the diagnosis and characterization of the disease severity of CAPS.

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CAPS and NLRP3

Article 15 April 2019

Abbreviations

CAPS:

Cryopyrin-associated periodic syndrome

CIAS1 :

Cold-induced autoinflammatory syndrome 1

CINCA:

Chronic infantile neurologic cutaneous and articular

CRP:

C-reactive protein

FCAS:

Familial cold autoinflammatory syndrome

HEK:

Human embryonic kidney

IL:

Interleukin

JIA:

Juvenile idiopathic arthritis

LPS:

Lipopolysaccharide

MWS:

Muckle–Wells syndrome

NLRP3 :

NOD-like receptor family, pryin domain containing 3

NF-κB:

Nuclear factor-κB

NOMID:

Neonatal-onset multisystem inflammatory disease

PBMCs:

Peripheral blood mononuclear cells

TNF:

Tumor necrosis factor

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Acknowledgements

We thank the members of the families who agreed to participate in the study. We thank Dr. T. Fukao, Dr. M. Kawamoto, Dr. N. Kawamoto, and K. Kasahara for their advice and technical help. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan and by Health and Labour Science Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare.

Conflicts of Interest

The authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
    Hidenori Ohnishi, Takahide Teramoto, Zenichiro Kato, Takeshi Kimura, Kazuo Kubota, Hideo Kaneko & Naomi Kondo
  2. Department of Dermatology, Graduate School of Medicine, Gifu University, Gifu, Japan
    Hiroaki Iwata & Mariko Seishima
  3. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Ryuta Nishikomori
  4. Department of Clinical Research, Nagara Medical Center, Gifu, Japan
    Hideo Kaneko

Authors

  1. Hidenori Ohnishi
  2. Takahide Teramoto
  3. Hiroaki Iwata
  4. Zenichiro Kato
  5. Takeshi Kimura
  6. Kazuo Kubota
  7. Ryuta Nishikomori
  8. Hideo Kaneko
  9. Mariko Seishima
  10. Naomi Kondo

Corresponding author

Correspondence toHidenori Ohnishi.

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Ohnishi, H., Teramoto, T., Iwata, H. et al. Characterization of NLRP3 Variants in Japanese Cryopyrin-Associated Periodic Syndrome Patients.J Clin Immunol 32, 221–229 (2012). https://doi.org/10.1007/s10875-011-9629-0

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