Date: Monday, October 22, 2018
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Sporadic Inclusion Body Myositis (sIBM) is an insidious onset, idiopathic inflammatory myopathy (IIM) with high morbidity. There has not been a reliable biomarker to aid in the diagnosis until autoantibodies to the 44 kDa cytosolic 5’-nucleotidase 1A (NT5c1A: Mup44) were reported. The objectives of our study were to determine the sensitivity and specificity of anti-NT5c1A for sIBM in a cohort of neuromuscular patients and to determine if indirect immunofluorescence (IIF) anti-nuclear antibodies (ANA) assay is a useful serological screen for anti-NT5c1A.
Methods: Sera from sIBM patients, various rheumatic and neuromuscular disease comparator groups, and apparently healthy controls were stored at -80C until required for analysis. All sIBM and IIM patients satisfied the 2017 EULAR/ACR classification criteria for IIM. IgG antibodies to NT5c1A were detected by an addressable laser bead immunoassay (ALBIA) using a full length human recombinant protein (Origene, Rockville, MD: Cat. #TP324617). Autoantibodies to other autoimmune inflammatory myopathy antigens were detected by line immunoassay (LIA) (Euroimmun GmbH, Luebeck, Germany), chemiluminescence assay (CIA) (Inova Diagnostics, San Diego, CA, USA) or enzyme linked immunoassay (ELISA). ANA was detected by IIF (Inova Diagnostics) on HEp-2 substrates. Demographic and clinical data was obtained by chart review.
Results: 27/43 (62.7%) of the sIBM sera were positive for anti-NT5c1A (sensitivity 0.63). 3/43 (7.0%) and 1/43 (2.3%) were positive for anti-SMN (Survival of Motor Neuron) and anti-HMGCR (3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase), respectively, but all were negative for the other myositis-related antibodies (Jo-1, OJ, TIF1y, PL-12, SAE, EJ, MDA5, PL7, SRP, NXP2, MI-2). By comparison, the frequency of anti-NT5c1A in the non-sIBM control group was 9% (specificity 0.91). Of note, 12/60 (20.0%) of systemic lupus erythematosus (SLE) patients were positive for anti-NT5c1A. Furthermore, the two IIM comparator groups (which did not include sIBM) showed 4/40 (10.0%) and 5/104 (4.9%) positivity for anti-NT5c1A. Review of ANA results for anti-NT5c1A positive (n=34) and anti-NT5c1A negative sera (n=37) indicated that there was no consistent IIF staining pattern associated with anti-NT5c1A positive sera, regardless of disease.
Conclusion: The sensitivity and specificity of anti-NT5c1A for IBM was 0.63 and 0.91, respectively. Therefore, a normal anti-NT5c1A test does not rule out sIBM (moderate sensitivity) whilst a positive test may be helpful with the canonical features of sIBM to support the diagnosis (high specificity). The clinical significance of anti-NT5c1A in SLE requires further study. Anti-NT5c1A antibodies were not associated with a specific IIF staining pattern, hence screening using HEp-2 substrate is unlikely to be a useful predictor for the presence of these autoantibodies.
To cite this abstract in AMA style:Amlani A, Tarnopolsky M, Brady L, Garcia de la Torre I, Mahler M, Choi M, Fritzler MJ. Anti-NT5c1A Autoantibodies As Biomarkers in Inclusion Body Myositis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/anti-nt5c1a-autoantibodies-as-biomarkers-in-inclusion-body-myositis/. Accessed March 28, 2020.
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