Performance of Antinuclear Antibody Immunoassays in Systemic Lupus Erythematosus Compared

In systemic lupus erythematosus (SLE), 3 antinuclear antibody assays (ANA) demonstrated commutability with a high proportion of positivity and titers or absorbance units (AU), according to study results published in Annals of the Rheumatic Diseases.

Previous research has indicated a significant discrepancy between various ANA assays, which can impact clinicians’ approach to diagnosis and follow-up.

In a longitudinal analysis, researchers compared 3 ANA assays among patients with incident SLE to further understand ANA detection and its clinical value.

Researchers collected demographic, clinical, and serologic data at study enrollment, year 3, and year 5, and performed 2 HEp-2 indirect immunofluorescence assays (IFA1, IFA2), including ANA enzyme-linked immunosorbent assay (ELISA) and SLE-related autoantibodies. The frequencies of positivity, titers or AU, and IFA patterns were compared.

Data from 805 patients with SLE were included in the study. The ANA positivity (≥1:80) at enrollment was found to be 96.1% according to IFA1 (median titer, 1:1280; IQR, 1:640 to 1:5120), 98.3% according to IFA2 (median titer, 1:2560; IQR, 1:640 to 1:5120), and 96.6% according to ELISA (176.3 AU; IQR, 106.4-203.5 AU). At study enrollment, at least 1 ANA assay showed a positive result for 99.6% of patients.

For IFA1 and IFA2, there was no significant change in ANA positivity at year 5 (95.2% and 98.9%, respectively), but ELISA positivity significantly decreased (difference, -5.3%; P <.001; 91.3% of patients tested positive). At all timepoints, researchers noted a greater than 91% agreement in ANA-positivity and at least 71% agreement in IFA patterns between IFA1 and IFA2.

Study limitations included potential selection bias for patients with SLE who tested ANA-positive; most patients had already been exposed to at least 1 immunomodulatory medication at enrollment; the study sample included a larger percentage of Asians and fewer Hispanic patients; only 3 from more than 10 types of ANA assays available were tested; and the duration of follow-up did not include potential seroconversions or assay performance later in disease.

Researchers concluded, “A clinical implication of this study is that for patients who have a moderate-to-high suspicion of SLE, especially those early in the disease course but without an established diagnosis, screening on both ELISA and HEp-2 IFA is warranted if one or the other provides results in the normal range.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Reference

Choi MY, Clarke AE, Urowitz M, et al. Longitudinal analysis of ANA in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Ann Rheum Dis. Published online March 25, 2022. doi:10.1136/annrheumdis-2022-222168