Background/Purpose: Antibodies to cytosolic 5’-Nucleotidase 1A (anti-cN1A or NT5C1A) are considered the only currently known serum biomarker for sporadic Inclusion Body Myositis (sIBM). They are reported in 33-76% of sIBM patients but little is known on their possible correlation with clinical, serological and histological features. Few studies have shown that anti-cN1A positive patients with sIBM present with a more severe phenotype and increased mortality risk.

Aims: To analyze the prevalence of anti-cN1A autoantibodies in a Swedish cohort of patients with sIBM by applying suspension antigen bead array and a commercially available ELISA assay. To explore whether the anti-cN1A autoantibodies could identify a distinct subgroup of sIBM with specific clinical or laboratory characteristics.

Methods: Reactivity to one N-terminal and one C-terminal protein fragment of the NT5C1A antigen was investigated by using a suspension bead array platform in serum samples from 46 patients with sIBM, 30 with Polymyositis (PM) and 30 with Dermatomyositis (DM), HLA matched. The ELISA kit was then used for 31/46 sIBM samples as well as in 33 DM and 43 PM samples. Plasma samples from 17 patients with Systemic Lupus Erythematosus (SLE) and 9 SLE-controls were also screened by ELISA. Clinical, serological and histological data of the sIBM cohort were collected at time of diagnosis and accumulated data during the disease course. The 46 sIBM patients were defined as having anti-cN1A antibodies if they tested positive by at least one of the two assays.

Results: The antigen bead array showed a sensitivity of 34.8% of identifying sIBM and a specificity of 83.3% when performed with the N-terminal fragment. The sensitivity decreased to 6,5% and the specificity increased to 93,5% when the test was run with the C-terminal fragment. The sensitivity and specificity for the ELISA assay were 41,9% and 74,5%, respectively. A statistically significant correlation was found between the ELISA and the antigen bead array results (N-terminal fragment) (Spearman’s rho 0.74, p value < 0.001). In the sIBM cohort, 19 seropositive and 27 seronegative to anti-cN1A antibodies were identified. No statistically significant differences in any of the analyzed variables were found between the 2 groups, but some interesting trends were observed. At time of diagnosis, seropositive patients had more frequently finger flexor weakness and reported higher score on patient visual analogue scale (VAS) for disease activity than the seronegative group. At first biopsy, increased amount of connective and/or fat tissue was found more commonly in anti-cN1A positive patients. More anti-cN1A positive than negative patients had positive history of falls and did not reach stabilization nor remission after the first year from diagnosis, independently of the use of immunosuppressive treatment.

Conclusion: Positivity to anti-cN1A antibodies is highly specific for sIBM diagnosis, as previously reported. The results from the antigen bead array suggest that the main epitope may be localized at the N-terminal region of the NT5C1A protein. In our cohort, anti-cN1A antibodies were not associated to any specific features but the seropositive group seemed to present with a more aggressive disease course.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antigen-bead-array-versus-elisa-to-detect-anti-cn1a-antibodies-in-patients-with-sporadic-inclusion-body-myositis-and-correlation-with-clinical-serological-and-histological-features/