AB0205 Expression of Inflammasomes is Different in Muscle of Dermatomyositis and Polymyositis Patients
Authors: Q. Zhao, Y. Zhang, T. Zhang, H. Zhou, X. Shu, X. Lu, G. Wang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Activation of innate immune plays important role in the pathogenesis of autoimmune disease. Nod-like receptors (NLRs) are cytosol-expressed pattern recognition receptors that can sense endogenous cellular products associated with tissue injury [1]. The activation of NLRs causes the formation and activation of inflammasomes, which are multi-protein platforms that mediate the activation of caspase-1, which can activate IL-1β[2,3]. Caspase-1 and IL-1b similarly distributed in muscles of dermatomyositis (DM) and polymyositis (PM) patients, suggesting a role of capase-1 in these diseases [4]. <h3>Objectives</h3> Our study was to investigate the expression of inflammasomes in muscle of DM and PM patients. <h3>Methods</h3> Immunohistochemistry was performed to determine the expression of NALP (NACHT-LRR-PYD-containing protein)1, NALP3, ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1 in muscle of 10 newly diagnosed and untreated adult DM/PM patients (4 DM and 6 PM) and 5 healthy controls. <h3>Results</h3> In muscle of 4 DM patients, ASC and caspase-1 were expressed in the plasma of CD3<sup>+</sup> T and CD20<sup>+</sup> B cells, while in 2 of them NALP3 was also expressed. Only 1 PM patient in 6 expressed NALP3, ASC and caspase-1 in the plasma of CD3<sup>+</sup> T and CD20<sup>+</sup> B cells. NALP1 was not expressed in all of the 10 patients. No NALP1, NALP3, ASC and caspase-1 were expressed in the muscle of 5 healthy controls. The positive rate of ASC and caspase-1 in DM group was significantly higher than that in PM and control group (<i>P</i>&lt;0.01 and <i>P</i>&lt;0.05), while the positive rate of NALP3 in DM group had no difference with that in PM and control group. The level of creatine kinase, erythrocyte sedimentation rate, C-reactive protein had no difference between NALP3, ASC and caspase-1 positive group and negative group. <h3>Conclusions</h3> Innate immune plays different role in the pathogenesis of DM and PM. Inflammasome participates in the inflammation of DM but not in PM, and may be activated by NALP3. <h3>References</h3> Franchi L, McDonald C, Kanneganti TD, et al. Nucleotide-binding oligomerization domain-like receptors: intracellular pattern recognition molecules for pathogen detection and host defense. J Immunol, 2006, 177(6): 3507-3513. Petrilli V, Dostert C, Muruve DA, et al. The inflammasome: a danger sensing complex triggering innate immunity. Curr Opin Immunol, 2007, 19(6): 615-622. Yu HB, Finlay BB. The caspase-1 inflammasome: a pilot of innate immune responses. Cell Host Microbe, 2008, 4(3): 198-208. Mackiewicz Z, Hukkanen M, Povilenaite D, et al. Dual effects of caspase-1, interleukin-1 beta, tumour necrosis factor-alpha and nerve growth factor receptor in inflammatory myopathies. Clin Exp Rheumatol, 2003, 21(1): 41-48. <h3>Acknowledgements</h3> The authors thank Dr. Pan Lin for her assistance with immunohistochemistry staining and Dr. Yaowen Zhang for statistical analysis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1931