PLASMA H3.1-NUCLEOSOMES TO CLASSIFY SEVERITY AND SURROGATE RESPONSE TO TREATMENT IN HIDRADENITIS SUPPURATIVA: A COHORT STUDY

ABSTRACT Background Huge neutrophilic infiltrates within lesional and perilesional tissue in hidradenitis suppurativa (HS) give rise to the hypothesis that neutrophil extracellular trap (NET) formation may further drive systemic immune activation in HS. As intrinsic constituents of NETs, nucleosomes-particularly circulating nucleosome containing Histone H3.1 (H3.1-nucleosomes)-serve as reliable indicators of NETosis in the blood. Objectives To investigate whether plasma H3.1-nucleosomes, fluctuate with HS activity. Methods Participants were adults with moderate to severe HS. Peripheral blood samples were collected at each visit, EDTA plasma was prepared under standardized conditions and stored at -80°C. They were subsequently analyzed for circulating H3.1-nucleosomes with a proprietary assay. Baseline and longitudinal data were evaluated in relation to HS severity, clinical characteristics and clinical response using both the HS clinical response score (HiSCR) and the at least 55% decrease of the international HS4 score (IHS4-55). Results 93 patients were enrolled; in serial measurements were available for 54. Patients were classified into two clusters; hyper-H3.1 and hypo-H3.1 based on the over-time kinetics of H3.1-nucleosomes. The hyper-H3.1 cluster is characterized by more severe disease. H3.1-nucleosomes 24 ng/ml or more suggest higher total count of inflammatory lesions and of draining tunnels. More than 45% decrease of H3.1-nucleosomes between visits is associated with higher chances for attainment of HiSCR and IHS4-55 responses with biologicals targeting TNFα, IL-1 and IL-17. Conclusions Circulating H3.1-nucleosome levels reflect HS disease activity and surrogate response to treatment. What is already know about this topic? Biomarkers to provide precision approach in hidradenitis suppurativa remain an unmet need. What does this study add? For the first time an easy-to-measure blood test is presented to classify patients and to surrogate treatment. H3.1-nucleosomes distinguish patients into high- and low-level of neutrophil activation. Over-time decreases by 45% or more indicate response to biological treatment. What is the translational message? The new blood test may be used to initiate trials where treatment guidance of both initiation and early stop of treatment will be studied.