Is anti-HMGB1 Antibody a Potential Characteristic Autoantibody for Sjögren's Syndrome?

Abstract BACKGROUND: Sjögren's syndrome (SS) is a common chronic inflammatory autoimmune disease, affects about 0.33% to 0.77% population in China. The positive for antinuclear antibodies (ANA) is one of the key features of SS, which show typical granular pattern in indirect immunofluorescent antibody test (IIFT). About 70% SS patients have the anti-SS-A and/or SS-B antibodies, which indicates other autoantibodies in SS patients.METHODS: The anti-HMGB1 antibody in 93 SS patients and 96 healthy controls were investigated with in-house built ELISA and immunoblotting; and the location of HMGB1 and fluorescent pattern of anti-HMGB1 antibody were investigated with IIFT. The contribution of anti-HMGB1 antibody in ANA-IF with Cas9-induce HMGB1 knockout cells were also detected.RESULTS: The anti-HMGB1 antibody in SS patients (9.96±5.55 VS 4.9±1.4 RU/ml RU/ml compared to healthy controls) increased. With ROC curve analysis, when taking 8 RU/ml as the cutoff value, the sensitivity, specificity, and the area under the curve were 64.5%, 96.9% and 0.83, respectively. A total of 18 patients (20.7%) with granular pattern in ANA-IF test were anti-HMGB1 antibody positive only. With commercial antibody, the fluorescent pattern of anti-HMGB1 antibody showed typical granular pattern. The serum from ANA-IF (+), SS-A (-), and SS-B (-) SS patients showed typical granular pattern in wildtype B16 cells, but no fluorescence in HMGB1 knockout B16 cells.CONCLUSIONS: Anti-HMGB1 antibody may be one of the characteristic autoantibodies of SS except anti-SS-A and SS-B. The detection of anti-HMGB1 antibody can provide more laboratory evidence for clinical diagnosis of SS.