Clinical Information

Based on their specificity, autoantibodies in idiopathic inflammatory myopathies (IIM) are grouped into myositis specific (MSA) and myositis associated autoantibodies (MAA).(1-3) Among the MSA, autoantibodies against aminoacyl-tRNA synthetases (aaRSs) represent the most common antibodies and can be detected in 25% to 35% of patients with mainly anti-synthetase syndrome (ASSD).(1-4) ASSD is an autoimmune disease characterized by the presence of autoantibodies targeting one of several aaRSs along with clinical features including interstitial lung disease, myositis, Raynaud's phenomenon, arthritis, mechanic's hands, and fever.(3,4) The family of aaRSs consists of highly conserved cytoplasmic and mitochondrial enzymes, one for each amino acid, which are essential for the RNA translation machinery and protein synthesis. Along with their main functions, aaRSs are involved in the development of immune responses, regulation of transcription, and gene-specific silencing of translation.(4)

Anti-Jo-1 autoantibody is the most frequently detected anti-aaRS antibody in ASSD and targets the histidyl tRNA synthetase which catalyses the binding of the histidine to its cognate tRNA during protein synthesis.(4,5). Other described anti-aaRSs reported in ASSD include PL-7 (threonyl), PL-12 (alanyl), OJ (isoleucyl), EJ (glycyl), KS (asparaginyl), Zo (phenylalanyl) and Ha (tyrosyl).(4) The presence these autoantibodies has become a key feature for classification and diagnosis of IIM and is increasingly used to define clinically distinguishable IIM subsets. Each anti-ARS antibody seems to define a distinctive clinical phenotype.(3)

In addition to the characteristic features associated with the presence of anti-Jo-1 antibodies in patients with ASSD, testing for anti-aaRS autoantibodies including anti-Jo-1 antibody maybe indicated with cytoplasmic speckled pattern using HEp-2 substrate by indirect immunofluorescence assay.(6,7) In the context of ASSD, their presence may be associated with positivity for anti-Ro52 antibodies which is an MAA.(8) In routine clinical testing, anti-Jo-1 antibody testing maybe performed using a variety of solid-phase immunoassays such as the enzyme-linked immunosorbent assay, line immunoassay, chemiluminescence immunoassay, fluorescent enzyme immunoassay, and multiplex immunoassay such as the BioPlex.(6,9,10) The performance characteristics of these assays for the detection of anti-Jo-1 antibody have not been extensively investigated to establish comparability.(9,10)

For more information see Connective Tissue Disease Cascade.