Background/Purpose:

High mobility group box 1 (HMGB1) is a damage-associated molecular pattern and can be divided in three separate domains: the A Box, B Box and the acidic tail. Box A by itself serves as a competitive antagonist for HMGB1 and inhibits HMGB1 activity. In an earlier study we showed that anti-HMGB1 antibodies are present in Systemic Lupus Erythematosus (SLE) patients and may play a role in the pathogenesis of the disease, but are not present in patients with systemic vasculitis. In this study we investigate the relation between anti-HMGB1 antibodies and disease activity, renal involvement, anti-dsDNA antibodies and medication use. We performed cross-sectional and longitudinal analyses.

Methods:

Seventy-one SLE patients, 25 age and sex matched healthy controls (HC), and 15 disease control patients with incomplete lupus (fulfilled less than 4 of the ACR criteria), were included in this study. All 71 SLE patients were measured during quiescent or mild (SLEDAI ≤ 4) disease, and 28 were also measured during an exacerbation (SLEDAI ≥ 5). Furthermore, in a subgroup of patients (n=11) longitudinal levels of HMGB1 were determined over a period of three years. Serum levels of anti-HMGB1 IgG and IgM were measured using an in house ELISA. Epitope recognition was measured by ELISA against Box A and B IgG. Data are presented as arbitrary units (AU).

Results:

Quiescent as well as active SLE patients showed a significant increase in anti-HMGB1 IgG compared to HC (median 236 vs 339 vs 46 AU respectively). Incomplete lupus patients also had an increased anti-HMGB1 level compared to HC (p=0.03), but lower compared to SLE patients (ns). Patients recognized both Box A and Box B epitopes of the molecule. Anti-HMGB1 IgM levels were not different in patients versus controls. We did find an association with disease activity, as there was a significant decrease in Box A recognition after exacerbation (p=0.028). No differences were found comparing active patients with renal involvement to patients without for anti-HMGB1 IgG, IgM, Box A and Box B. There was also no effect of immunosuppressive medication, including hydroxychloroquine, on anti-HMGB1 levels. Finally, longitudinal values of anti-HMGB1 IgG showed similar patterns compared to anti-dsDNA and might even increase shortly before an increase in anti-ds DNA levels are seen.

Conclusion:

Anti-HMGB1 antibodies seem specific for SLE, as they were significantly increased compared to HC. Interestingly, also incomplete lupus patients showed already a minor increase of anti-HMGB1 antibodies. Antibodies directed to Box A decreased after an exacerbation, indicating a correlation with disease activity. Furthermore, longitudinally levels of anti-HMGB1 seemed to increase before an increase in anti-dsDNA levels occurred, which might indicate an interesting new biomarker in the follow-up of SLE patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibodies-against-high-mobility-group-box-1-hmgb1-in-patients-with-sle/