Plasma high-mobility group nucleosome-binding domain 1 (HMGN1) protein levels in four common rheumatic diseases: A potential biomarker of rheumatoid arthritis

Abstract

Aim of the work: Non-histone chromosomal protein, high-mobility group nucleosome-binding domain 1 (HMGN1), is assumed to be a potential alarmin involved in the activation of inflammatory responses in rheumatic diseases, but the blood concentration of this protein is unknown. In this study, the plasma concentration of HMGN1 was investigated in four common rheumatic diseases compared to healthy individuals and between diseases. Patients and methods: A total of 39 age-matched rheumatoid arthritis (RA) patients, 64 ankylosing spondylitis (AS) patients, 30 psoriatic arthritis (PsA) patients, 26 systemic lupus erythematosus (SLE) patients and 59 healthy subjects were included in the study. HMGN1 concentration was determined by enzyme-linked immunosorbent assay. Results: HMGN1 concentration was above the minimum detectable level in 7 % of healthy individuals, 12 % of SLE, 17 % of PsA, 36 % of AS, and 82 % of RA patients. The remaining participants had HMGN1 concentrations close to zero. The odds ratio for HMGN1 detection in RA was 62.9 (95 % CI: 17.1–231.4, p < 0.00001) and in AS was 7.7 (95 % CI: 2.5–24.0, p = 0.00008). The median HMGN1 concentration in RA (1.36 [Q1, Q3: 0.21, 2.85]) was significantly higher than in healthy individuals (0 [0,0] ng/mL, p < 0.00001) and patients with other rheumatic diseases (p < 0.00001). HMGN1 levels were also increased in AS patients (0 [0, 0.21] ng/mL, p = 0.00006) compared to controls, but to a lesser extent than in RA. HMGN1 concentration in SLE and PsA patients did not differ from healthy subjects. HMGN1 showed good diagnostic potential as a predictor of RA patients and healthy individuals (AUC: 0.87, 95 %CI: 0.79–0.95, p < 0.00001). HMGN1 level correlated only with DAS28 score in RA (r = 0.44, p = 0.02), although multiple regression analysis identified only erythrocyte sedimentation rate as a predictor of DAS28 but not HMGN1 level. Conclusion: HMGN1 can be considered as a promising differential biomarker of RA. More sensitive tests for HMGN1 levels are needed for accurate diagnosis. Furthermore, studies on the role of HMGN1 in RA pathogenesis are needed in light of these findings.