Background High mobility group box protein 1 (HMGB1) is a nuclear DNA-binding protein that can function as an alarmin when is released from activated and dying cells. In association with nucleosomes, HMGB1 may contribute to the pathogenesis of systemic lupus erythematosus (SLE). Some previous reports have associated HMGB1 with the pathogenesis of cutaneous lupus and lupus nephritis (LN). HMGB1 may also be contained in microparticles (MPs). These vesicles have a wide spectrum of biological activities in intercellular communication, and they compete with apoptotic cells to bind mononuclear phagocytes.
Objectives To evaluate the association of MP-HMGB1+ circulating with LN and to correlate them with LN activity.
Methods Blood samples from 60 SLE patients were used to isolated MPs from platelet-poor plasma by centrifugation and their count, cell source and phenotype were characterized by flow cytometry. Renal pathology was reported using the standardized International Society of Nephrology/Renal Pathological Society classification. Inactive lupus nephritis (LN) was defined by the presence of one or more of the following criteria: 24 hrs proteinuria 500 mg/dl or inactive urine sediments (<5 red cells/HPF) and no red cell casts and no leucocyturia (<5 white cells/HPF) and stable serum creatinine.
Results Mean age of SLE patients was 31.9±10.8 years, and mean disease duration was 7.8±6.2 years. 73% patients had LN and 89% were female. Patients with LN had significantly higher frequency of MP-HMGB1+, no significant differences were found among patients with active versus inactive LN or among patients with proliferative vs non-proliferative LN; MP-HMGB1+ had a moderate positive correlation with disease activity (SLEDAI, r=0.367, p=0.020), anti-C1q antibodies titers (r=0.42, p=001) and 24 hours proteinuria (r=0,33, p=,032), but no correlation was found with activity or chronicity indexes on renal biopsies. A ROC curve for MP-HMGB1+ and renal involvement showed a good discriminative ability (AUC 0.706). A cutoff of 15.7% of MP-HMGB1+ showed the best discrimination threshold with a sensitivity of 63.3% and specificity of 83.3%.
Conclusions In our cohort of patients with SLE, MP-HMGB1+ was significantly higher in patients with LN and in patients with active disease. Given the multiple implication of HMGB1 in SLE, including the active kidney recruitment of mononuclear phagocytes, we consider that MP-HMGB1+ could be considered as a potential biomarker for LN in SLE patients.
Harris, H. E. et al. HMGB1: A multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol. 8, 195–202 (2012).
Zickert, A. et al. Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis. Arthritis Res Ther. 20;14(1):R36 (2012).
Acknowledgements C. Burbano is recipient of a doctoral scholarship from COLCIENCIAS (call 617–2013). The authors are grateful to the grants “Sostenibilidad and Sistema Universitario de Investigaciones, CODI (2013–05–42869836) from Universidad de Antioquia, and to COLCIENCIAS (111565740575)”.
Disclosure of Interest None declared