Is high titre ANA specific for connective tissue disease?

A positive antinuclear antibody (ANA), while sensitive, is not specific for systemic lupus erythematosus or connective tissue diseases (CTD). The purpose of the present study was to review those sera with a high titre (> or = dilutions above screening) ANA and determine from a review of the charts if these higher titres offered a satisfactory specificity for CTD.

All FANA testing in this region is carried out in one of two related laboratories. We reviewed the medical records of patients who had a positive ANA at a titre 4 dilutions above screening at this city-wide laboratory over a 6-month period to determine whether this titre ("high titre") may offer relative diagnostic certainty. Antibodies to extractable nuclear antigens (ENA) and native DNA were also obtained.

422 ANA results were positive at high titre. The medical record was available for review in 320 patients, of whom 238 (75%) were seen by a specialist physician, almost always including a rheumatologist. Our review determined that 35% had a diagnosis of connective tissue disease, 21% had a diagnosis of a possible/probable inflammatory disease, 16% had an alternative specific diagnosis provided, and in 29% no final disease specific diagnosis was recorded but CTD was not suggested to us or the specialist by the data available. One or more anti-ENA antibodies and/or anti-DNA were positive in 69 (22%) and 8% of the sera tested respectively.

While long term follow-up is still required, a significant proportion of patients with high titre ANA have no CTD at the time of testing. Setting a higher cutoff for reporting of ANA may not increase specificity sufficiently to make it a useful alternative or addition to reporting a positive or negative value at screening titre alone.