Magnitude of SARS-CoV-2 Antibody Production and Its Relationship with Autoantibody Formation

SARS-CoV-2 infection induces virus-specific antibody production, and in some cases, these antibodies may cross-react with self-antigens, contributing to the development of autoantibodies. This raises the possibility that the magnitude of the antibody response may be associated with the emergence of antinuclear antibodies (ANAs). This study aimed to investigate the relationship between SARS-CoV-2 antibody levels and ANA positivity.

SARS-CoV-2 antibodies were quantified using an enzyme-linked immunosorbent assay (ELISA) kit with a dynamic range of 1-475 RU/mL. The positivity threshold was 10 RU/mL, and high SARS-CoV-2 antibody levels were defined as >235 RU/mL (>75% Bo/B in the calibration curve). Samples from individuals with chronic diseases were excluded. Because the number of highly positive samples was limited, these samples were identified first, and negative and moderately positive groups were then formed through random selection. Antinuclear antibodies, including anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENA), and anti-HEp-2 nucleus antibodies, were measured using commercial ELISA kits.

A total of 1222 samples were screened. After excluding 246 samples, 976 remained eligible. The mean ANA levels and positivity rates for the negative, positive, and high-positive groups were as follows: dsDNA, 0.75 (14.9%), 0.55 (7.5%), 0.85 (29.9%); ENA, 0.75 (14.9%), 0.55 (7.5), 0.85 (29.9%); and Hep-2 nucleus, 0.75 (14.9%), 0.55 (7.5%), 0.85 (29.9%). The high-positive group had significantly higher ANA levels and ANA positivity rates compared with the negative and moderate-positive groups (p<0.001). Notably, the moderately positive group had lower ANA levels and positivity rates than the negative group (p<0.001).

The findings suggest that ANA production may increase in individuals with a very high SARS-CoV-2 antibody response, while lower ANA levels were observed in those with a moderate antibody response. These results indicate that the relationship between virus-specific antibody magnitude and autoantibody development is more complex than expected. Given the clinical and immunological implications, further comprehensive studies are needed to clarify the underlying mechanisms.