To evaluate the prevalence of antibodies to 21-hydroxylase (anti-21[OH]), a marker of autoimmune adrenal disease, in a cohort of patients with primary Sjögren's syndrome (SS) and to investigate whether the presence of anti-21(OH) correlates with clinical, serologic, and salivary gland features of the disease.
Sera from 63 consecutive patients with primary SS, 32 patients with autoimmune thyroid disease (AITD), and 20 healthy controls were obtained and anti-21(OH) levels were determined by radioimmunoassay. Clinical, serologic, and histopathologic features were recorded, and a short Synacthen test was used to assess adrenal function reserve. Seven available minor salivary gland (MSG) tissue specimens from patients in the primary SS cohort were also assessed for interferon-α (IFNα), BAFF, and interleukin-21 (IL-21) cytokine transcripts, which are all implicated in B cell activation.
Anti-21(OH) positivity was detected in 17.5% and 28.1% of primary SS and AITD patients, respectively, and in none of the healthy controls. While no evidence of adrenal insufficiency was detected in any of the patients studied, a blunted rate of increase in cortisol levels was observed in patients with detectable serum autoantibodies against 21(OH), compared to their anti-21(OH)-negative counterparts. A strong correlation between the serum titer of anti-21(OH) antibodies and expression of IFNα, BAFF, and IL-21 messenger RNA in MSG tissues was also detected.
Adrenal autoimmunity occurs in almost 20% of patients with primary SS in association with markers of B cell activation. Although the presence of adrenal autoantibodies was not associated with adrenal insufficiency in the present study, there was a blunted adrenal response, suggesting the need for further followup and monitoring of adrenal function in patients with primary SS who are positive for the autoantibodies.