Skip to content

Advertisement

  • Poster presentation
  • Open Access

Temporal changes of serum cytokine/chemokine levels in patients of Nakajo-Nishimra syndrome treated with tocilizumab

  • 1,
  • 1,
  • 1,
  • 1,
  • 1 and
  • 2
Pediatric Rheumatology201513(Suppl 1):P169

https://doi.org/10.1186/1546-0096-13-S1-P169

Published: 28 September 2015

Keywords

  • Tocilizumab
  • Blood Monocyte
  • Lipodystrophy
  • Ubiquitinated Protein
  • Peripheral Blood Monocyte

In Nakajo-Nishimura syndrome (NNS), proteasome disability due to a loss-of-function PSMB8 mutation induces storage of ubiquitinated proteins and overproduction of inflammatory cytokines and chemokines. However, the precise mechanisms causing complex phenotypes of the disease, including pernio-like eruptions, lipodystrophy and calcification of basal ganglia, is mostly unclear. As IL-6 overproduction in association with p38 hyperactivation was supposed to have a role in NNS (Arima et al, PNAS 2011), tocilizumab, a monoclonal antibody for IL-6 receptor, has recently been applied for two patients with NNS after informed consents were obtained. Decreased serum CRP and CPK levels in both patients and improved myalgia and arthralgia in one patient have been observed, whereas none of decrease in serum LDH level or improvement of fever and eruptions have been achieved. By analysis of serum cytokine/chemokine levels, IL-6, G-CSF and MCP-1 levels have changed in accordance to the CRP level, whereas IP-10 has shown constantly high levels independent of the CRP level. Furthermore, both the patients-derived peripheral blood monocytes and monocytes differentiated from a patient-derived iPS cells produced higher level of IP-10 than control cells after IFNgamma stimulation. These findings suggest that monocyte-derived IP-10 has a major role in pathogenesis of the sustained/progressing phenotypes in NNS.

Authors’ Affiliations

(1)
Department of Dermatology, Wakayama Medical University, Wakayama, Japan
(2)
Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan

Copyright

© Kanazawa et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement