Myositis-specific autoantibodies could aid inflammatory myopathy classification
medwireNews: Some subgroups of patients with myositis-specific autoantibody (MSA)-positive inflammatory myopathies (IMs) are “frequently misclassified” based on currently used criteria, and adopting an autoantibody-based system may improve classification, researchers report.
Andrew Mammen (National Institutes of Health, Bethesda, Maryland, USA) and co-authors explain that the 2017 EULAR/American College of Rheumatology (ACR) classification criteria are “based on a set of epidemiologic, clinical, and laboratory variables,” but these criteria “do not utilize MSAs other than anti-Jo1” because serologic tests were not widely available when they were developed.
In their study, Mammen et al found that 91% of 524 MSA-positive individuals with IM from a US cohort were correctly classified using the EULAR/ACR criteria, but the accuracy of the criteria “was not uniform across the different MSAs.”
The 47 patients who were incorrectly classified as not having IM included 20% of the 122 individuals positive for anti-HMGCR autoantibodies and 9% of the 44 with anti-SRP positivity. Moreover, among those who were positive for both of these MSAs and correctly identified as having IM using the EULAR/ACR criteria, approximately 10% were incorrectly subclassified as having inclusion body myositis (IBM) due to distal weakness, treatment resistance, and/or muscle biopsies with vacuolar changes.
The study authors then evaluated whether MSAs could predict IM phenotypes, finding that the presence of different MSAs can be used to divide patients into five distinct categories of muscle involvement at baseline and evolution over time. Factor analysis of mixed data – carried out to mathematically summarize individual patient clinical phenotypes – showed that people within each MSA-defined group had similar phenotypes. On the other hand, these analyses showed that “a significant amount of information on relevant myositis subgroups may be lost” when using the four classification groups in the EULAR/ACR criteria.
Additionally, Mammen et al used analytical tools based on information theory to show that MSAs outperform the existing EULAR/ACR criteria for the prediction of clinical phenotypes.
“Taken together, these analyses strongly support using MSAs to help subclassify myositis patients into phenotypically homogeneous groups,” they write in Arthritis & Rheumatology.
Based on these findings, the researchers developed a simple set of diagnostic criteria based on the presence of MSAs and clinical variables, which had “perfect sensitivity and specificity” for the identification of MSA-defined IM subgroups in two validation cohorts from the USA (n=109) and Spain (n=342).
“These criteria could be easily updated as new autoantibodies are discovered,” they say.
The team concludes: “Although challenging, we propose that confirming these results in additional myositis cohorts and revising the IM classification criteria to utilize MSAs should be priorities of the international myositis community.”
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