Evaluation of serum markers of the immune response and bone metabolism facilitates early detection of psoriatic arthritis in patients with psoriasis

Abstract

Relevance: Psoriatic arthritis (PA) is a severe complication of psoriasis, leading to progressive damage to the musculoskeletal system, a decrease in the quality of life and early disability. CASPAR criteria, widely used for PA diagnosis, are highly sensitive and specific. However, some patients with psoriasis score 3 with CASPAR criteria without an established PA diagnosis. At present, there is a search for PA biomarkers, which could mirror the stages of pathogenesis of joint and enthesis destruction in this disease.
 Aim: To identify the most significant changes in biochemical parameters in patients with PA, that would be pathophysiologically associated with the disease.
 Materials and methods: We performed an open label comparative parallel groupstudy in 60 patients with PA and 40 patients with psoriasis without PA. Clinical assessments included filling in the questionnaires, past history, dermatologist consultation, severity of psoriasis by PASI, and PA activity. Clinical chemistry examination included the levels of antibodies to citrullinated peptide, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen HLA B27, immunoglobulins A, M, and G, complement system components C3, C4, circulating immune complexes (CIC), as well as bone metabolism parameters (calcium, phosphorus, magnesium, seromucoid, alkaline phosphatase (AP), osteocalcin, parathyroid hormone, vitamin D, matrix metalloproteinases MMP-1, MMP-3, MMP-8, and cartilage oligomeric matrix protein (СОМР).
 Results: Psoriasis was diagnosed in 86.6% (n=52) of the patients with PA. Family history of psoriasis was confirmed in 55.0% (n=22) of the patients with psoriasis without PA and in 60.0% (n=36) of the patients with PA (p=0.681). Compared to the patients with psoriasis without PA, the patients with PA had higher prevalence of psoriatic onychodystrophy (71.6%, n=43, vs. 35.0%, n=14, p=0.0004), dactylitis (28.3%, n=17, vs. 5.0%, n=2, p=0.004), extra-articular bone proliferation signs (26.6%, n=16, vs. 5.0%, n=2, p=0.006). In the patients with PA, compared to those without PA, there was a significant increase in CRPlevels (27.4 vs. 9.5 mg/l, p=0.002), more than 2-fold increase in IgM and IgG (IgM, 2.35 vs. 1.2 g/l, p=0.023; IgG, 17.7 vs. 8.45 g/l, p 0.0001), and CIC (89.3 vs. 29.5 mU/ml, p=0.0003). Serum phosphorus and magnesium levels in the patients with PA were lower than in the psoriasis patients without PA (phosphorus 0.8 vs. 1.6 mmol/l, respectively, p=0.045, magnesium 0.5 vs. 1.0 mmol/l, respectively, p=0.001), with somewhat higher parathyroid hormone levels (67.3 vs. 25.1 ng/ml, respectively, p=0.013). Osteocalcin levels in the PA patients were by 37.3% lower than in the patients with psoriasis without PA (17.57 vs. 24.13 ng/ml, respectively, p=0.004). MMP-1 levels in the PA groupwere 12.3-fold higher than in the non-PA group(37.68 vs. 3.05 ng/ml, respectively, p 0.0001), and MMP-3 levels were 3.7-fold higher (42.35 vs. 11.36 ng/ml, respectively, p=0.022). In the patients with PA, APlevels were 2.52-fold higher than in the control group(150.2 vs. 59.5 U/ml, respectively, p=0.007), and COMPlevels were 2.08-fold higher (415.2 vs. 199.5 ng/ml, respectively, p=0.006).
 Conclusion: The patients with PA have higher serum CRP, IgM, IgG, CIC, MMP-1, MMP-3, AP, and COMPlevels and lower osteocalcin, phosphorus, and magnesium concentrations, than the patients with psoriasis. These parameters are not PA-specific; however, the search for the most sensitive biomarkers of the systemic immune response and bone remodeling seems to be a promising area of research, since identification of such markers would allow for timely prediction and detection of PA in patients with psoriasis.