Background Recent reports had shown that most of clinically amyopathic dermatomyositis (CADM), which showed poor prognosis, was positive for anti-Melanoma differentiation-associated gene 5 (MDA5) antibody (Ab). It had been shown that patients not only with lupus but with dermatomyositis (DM) also showed increased type 1 interferon (IFN) signature. MDA5 acts as a cytosolic RNA sensor, which drives type 1 IFN production. These facts suggested that type 1 IFN might have some roles in anti-MDA5 Ab positive patients.
Objectives We evaluated the association of serum type 1 IFN signature and autoantibodies in patients with inflammatory myositis, in particular anti-MDA5 Ab positive patients and anti-aminoacyl-tRNA synthetases (ARS) Ab positive patients.
Methods Sera from 33 inflammatory myositis patients (13 DM, 10 PM and 10 CADM) were studied for type 1 IFN activity, using a functional reporter cell assay. Briefly WISH cells were incubated with serum containing media for 6 hours. Serum IFN signature scores of the incubated cells were evaluated by the sums of gene expressions of Mx1, IFIT3, IFI44L and IFI44 by real time PCR (Reference). Anti-MDA5 Ab and Anti-ARS Ab were measured by ELISA. We divided these patients into three groups, anti-MDA5 Ab positive group (MDA5 group), anti-ARS Ab positive group (ARS group) and double negative group (DN group). We included double positive patients into MDA5 group. The presence of interstitial lung disease (ILD) and the prognosis were also investigated.
Results MDA5 group had 12 patients (8 CADM and 4 DM), ARS group had 8 patients (4 DM, 1 CADM and 3 PM), and DN group had 13 patients (5 DM, 1 CADM and 7 PM). 9 of MDA5 group, 5 of ARS group, and 1 of DN group were complicated with ILD. Serum IFN signature scores of MDA5 group were significant higher than those of ARS group and DN group (12.43 1.406, 2.407, p=0.0005). The most of ARS group showed low serum IFN signature activities. The overall survivals of ARS group were fairer than MDA5 group, but not significantly. The deceased cases of MDA5 group showed especially high serum IFN signature activities.
Conclusions We characterized two major groups in inflammatory myositis patients. ARS group was characterized by low IFN signature with the susceptibility to DM and ILD. MDA5 group was characterized by high serum IFN signature with the high susceptibility to CADM. Our results suggest that these two entities may have different onset mechanisms, leading to different outcomes.
Niewold TB, Rivera TL, Buyon JP, Crow MK. Serum type I interferon activity is dependent on maternal diagnosis in anti-SSA/Ro-positive mothers of children with neonatal lupus. Arthritis Rheum. 2008 Feb;58(2):541–6.
Disclosure of Interest None declared