Novel Serology Testing for Sporadic Inclusion Body Myositis

Disease-Specificity and Diagnostic Utility

Megan K. Herbert; Ger J.M. Pruijn

Disclosures

Curr Opin Rheumatol. 2015;27(6):596-600. 

In This Article

Disease-specificity and Diagnostic Utility of Anti-cytosolic 5'-nucleotidase 1A Auto-antibodies

The identification of cN-1A as the prime target for auto-antibodies in sIBM sera and the high prevalence of anti-cN-1A auto-antibodies have been exciting breakthroughs in the search for auto-antibody biomarkers for sIBM. Indeed, the recent ELISA studies[21,22] consistently demonstrate that anti-cN-1A auto-antibodies are more prevalent in sIBM compared with polymyositis or dermatomyositis, other neuromuscular disorders and most other autoimmune diseases (see data described above). In light of these findings, anti-cN-1A auto-antibodies provide utility in distinguishing sIBM from polymyositis and dermatomyositis, an important distinction when determining therapy regimes, considering that polymyositis and dermatomyositis, but not sIBM, are typically responsive to immunosuppressive medications.

Although anti-cN-1A auto-antibodies are rare in other forms of myositis and in other rheumatic and neuromuscular disease, they are not specific for sIBM. Rather, we also frequently detected anti-cN-1A auto-antibodies in the sera of patients with Sjögren's syndrome (SjS; 37%) and systemic lupus erythematosus (SLE; 20%).[22] Although the numbers of samples analysed were rather small (22 and 44, respectively), a subsequently published study, using immunoblotting-based assays with a somewhat larger cohort of SjS and SLE patients (44 and 96, respectively), has recently confirmed these findings. In the latter study,[19] anti-cN-1A seropositivity was found in 20% of SjS and 14% of SLE patients. Although different methodologies were used to detect anti-cN-1A auto-antibodies in these studies, the results are consistent. Standardized testing will need to be introduced in the future in order to make better comparisons between data obtained with different cohorts and to fully investigate the prevalence of anti-cN-1A auto-antibodies in myositis and other (inflammatory) diseases. Furthermore, as already described above, we came across frequent low-level reactivity in a broad range of patient sera. We therefore chose high cut-off levels in order to optimize the specificity of our peptide ELISAs to at least 97%. The latter phenomenon was not only observed in the peptide ELISA, but also for the immunoprecipitation of in-vitro translated recombinant, full-length cN-1A. The consequence of choosing a cut-off with high sensitivity could be an increase in the number of false-negatives. Perhaps, this issue could be resolved or improved by determining antibody titres rather than defining arbitrary cut-offs. In addition, this phenomenon further underscores the necessity for fully optimized and standardized testing procedures.

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