Background and Aims

Anti-RA33 antibodies have been observed in seronegative patients, and thus may provide added diagnostic value in early rheumatoid arthritis (RA).

Methods

134 sera from an investigation cohort (Vienna early RA cohort) and a validation cohort (Leeds early RA cohort) of 131 patients (both satisfying 2010 ACR/EULAR classification criteria) were tested for the presence of IgA, IgG and IgM isotypes of anti-RA33 antibodies by prototype assays using the EliA™ platform (Thermo Fisher Scientific). The cut-off values were chosen to achieve specificities of ≥95% against disease controls and 98% against healthy subjects*. In addition, RF-IgM as well as ACPA-IgG was detected by EliA™ (Thermo Fisher Scientific).

Results

In the investigation cohort anti-RA33 antibodies were detected in 8 out of 51 seronegative patients, reducing the ‘serological gap’ left by RF and ACPA routine testing by 15.7%. The anti-RA33 IgM isotype showed the highest sensitivity (10%) followed by IgG (6%) and IgA (3.7%) isotypes. Interestingly, the prevalence of anti-RA33 antibodies in the validation cohort was considerably higher without differences in titer. The highest sensitivity was found for the anti-RA33-IgG isotype (20.6%) followed by IgA (16%) and IgM (14.5%). Disease duration might have influenced the different distribution of anti-RA33 isotypes as as it ranged from 0.2 years (investigation cohort) 0.6 years (validation cohort). The added diagnostic value in the validation cohort was 24.5%.

Conclusions

Results suggests anti-RA33 antibody testing may aid in the diagnosis of (otherwise labelled seronegative) early RA. Furthermore disease duration might impact the distribution of anti-RA33 antibody isotypes.

* Sieghart et al. Front Immunol. 2018