Abstract 2070: Autoantigen Microarray Analysis of Sera from Juvenile Dermatomyositis Patients: Association with an SLE-like Type I Interferon Signature
Authors
Imelda Balboni1, Pinakeen Patel2, Cindy Limb3, Nicola Luera3, Gabrielle Morgan4, Paul J. Utz3, Virginia Pascual2, Lauren M. Pachman4.
Purpose
To identify characteristic autoantibody profiles in children with Juvenile Dermatomyositis (JDM), using autoantigen microarrays, to provide insight into disease classification.
Methods
Sera from 37 consented children with definite JDM negative for myositis antibodies, and 10 age- and sex-matched controls were tested using a 1040-feature autoantigen microarray with approximately 80 autoantigens associated with several connective tissue diseases. Microarrays were probed with 1:150 dilutions of serum and a goat-anti-human IgG & IgM secondary antibody, scanned and analyzed to determine median fluorescence intensity minus background (MFI-B) for each antigen. Significance Analysis of Microarrays (SAM) software was used to determine differences in autoantibody expression in JDM versus normal controls and in subgroup analyses including ANA status, high versus low disease activity scores (DAS), and full versus partial interferon (IFN) signature. IFN signature was determined by Biotinylated cRNA targets, purified and hybridized to Affymetrix HG-U133A and U133B GeneChips 7.3, was used to perform statistical analysis and clustering.
Results
Significance Analysis of Microarrays (SAM) did not identify significant differences in autoantibody expression between JDM and normal controls, or on subgroup analyses of ANA positive versus negative patients or those with high versus low DAS for weakness or skin. SAM comparing serum samples from JDM patients with a previously-identified full versus partial IFN signature in peripheral blood mononuclear cells revealed that patients with a full IFN signature had increased reactivity to several autoantigens including Ro-52 (2.2 fold increase), recombinant Ro- 60 (3.4 fold increase), bovine Ro-60 (7.6 fold increase), La (3.1 fold increase), and B/B’ (2 fold increase) with q-values of zero, indicating statistical significance.
Conclusions
Autoantibody profiles of JDM patients with a full IFN signature are similar to those found in SLE and differ from JDM patients with a partial signature. The sera reactivity identified several RNAcontaining antigens that are targeted in SLE and other connective tissue diseases. Since members of the Toll-like receptor (TLR) family are involved in the induction of type I IFNs and several TLRs recognize RNA, this group speculates that there is a possible role for RNA-containing antigens as well as TLR activation in this JDM subgroup.
Editorial Comment
The interferon signature has been recognized in many autoimmune diseases, including SLE. Given that members of the Toll-like receptor (TLR) family are involved in the induction of type I IFNs and several TLRs recognize RNA, the group contends that there may be a possible role for RNA-containing antigens as well as TLR activation in the JDM subgroup, a finding not previously seen.
