Volume 13 Supplement 1

8th International Congress of Familial Mediterranean Fever and Systemic Autoinflammatory Diseases

Open Access

Beneficial effect of methotrexate on a case of Nakajo-Nishimura syndrome

  • K Kunimoto1,
  • F Ozaki2,
  • F Furukawa1 and
  • N Kanazawa1
Pediatric Rheumatology201513(Suppl 1):P199

https://doi.org/10.1186/1546-0096-13-S1-P199

Published: 28 September 2015

Nakajo-Nishimura syndrome (NNS) is a very rare autosomal recessively-inherited autoinflammatory disorder that onsets in infancy with pernio-like rashes and gradually develops into partial lipodystrophy, accompanied with remittent fever and nodular skin eruptions. This disease is caused by a unique mutation of the PSMB8 gene, which not only impairs an enzymatic activity of the encoding beta5i subunit, but also disturbs formation of the immunoproteasome complex. As the pathogenesis for NNS, cellular accumulation of ubiquitinated and oxidized proteins due to immunoproteasome deficiency is considered to cause MAP kinase activation with nuclear accumulation of phosphorylated p38 and following IL-6 production.

The treatment for Nakajo-Nishimura syndrome has not been established. Inflammatory attacks can temporarily respond to the oral administration of high-dose corticosteroid, but they easily recur by tapering the dose of corticosteroid. Furthermore, the high-dose corticosteroid therapy has various side effects such as growth failure in infancy. In our child case of NNS (Kunimoto et al, Dermatology 2013), additional administration of methotrexate (MTX) significantly decreased a frequency of febrile attacks, in comparison to the treatment with oral corticosteroid alone. Notably, effectiveness of MTX was previously described on some infant cases of CANDLE syndrome, another PSMB8-mutated proteasome-associated autoinflammatory syndrome (PRAAS). MTX is known to execute anti-inflammatory effects through inhibition of folic acid-dependent enzymes, including dihydrofolate reductase (DHFR) and aminoimidazole carboxamide ribonucleotide transformylase (ATIC). ATIC inhibition causes accumulation of intracellular aminoimidazole carboxamide ribonucleotide and inhibits AMP deaminase, to increase the production of adenosine. Adenosine can inhibit superoxide production of neutrophils and their attachment to endothelial cells. As preliminary results, increased ROS production has been observed in primary neutrophils of NNS patients, suggesting one of the points that MTX affects.

Authors’ Affiliations

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

Copyright

© Kunimoto 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