Antibodies to ab blood group antigens mimic anti-salivary duct autoantibodies in patients with limited sicca symptoms

Objective. We evaluated the clinical relevance and pathogenic significance of anti-salivary duct autoantibodies (ASDA) in Sjogren's syndrome (SS) and rheumatoid arthritis (RA) by examining (1) their frequency in healthy controls, patients with sicca symptoms, and patients with various autoimmune and infective disorders; (2) their localization by confocal microscopy; and (3) their tissue distribution and cross reactivity with blood group antigens. Methods. Indirect immunofluorescence (IF) was performed on commercial cryostat sections of monkey parotid salivary gland. Sections were examined by fluorescence and confocal laser scanning microscopy. Sera giving positive staining on the ducts were tested by IF on a range of monkey tissues and salivary glands from several mammalian species. Blocking experiments were performed with human erythrocytes of different ABO blood groups and AB antigens. Results. We identified 2 distinct ductal staining patterns. The first resembled ASDA described in earlier studies and showed patchy bright staining of the apical (luminal) surfaces of the ducts and staining of apical cytoplasmic vesicles. The other was only observed with anti-mitochondrial antibody positive sera and stained the mitochondrial-rich ductal epithelium in a distinctive punctate pattern. Antibodies staining the apical surface of ducts were detected rarely in patients with anti-Ro/La autoantibody-positive primary SS (1/76) and RA (1/36) and were found in only 1/15 with RA and secondary SS. ASDA were detected in sera from 13/51 (25.5%) of patients referred to our clinic with limited sicca symptoms who were anti-Ro/La antibody-negative and had no typical clinical or laboratory features of classical primary SS. The apical ductal staining pattern was not observed with sera from 63 healthy controls without sicca symptoms or in patients with autoimmune and infective disorders. Twelve of the 13 patients whose sera gave ASDA-like staining were blood group O and one group A. Ductal staining was abolished in all sera after absorption with blood group AB erythrocytes or AB antigen. In 5 patients ductal staining was removed by absorption with B erythrocytes but not with A erythrocytes; in the remainder ductal reactivity was abolished by both A and B erythrocytes. Conclusion. ASDA seem to occur rarely in patients with primary SS and RA. However, isotype switched lgG AB blood group antibodies cross react with primate salivary ducts and may produce false positive ASDA staining. Detection of ASDA may be of value in identifying a subset of patients who present with mild sicca symptoms without other autoimmune features.