The relationship of serum elafin levels with disease activity and systemic involvement in behçet's disease

Background and Objective: Behçet's disease is a vasculitic disease characterized by recurrent oral aphthous ulcers, genital ulcers, and uveitis, along with a diverse range of symptoms associated with the involvement of almost every organ system. The diagnosis and follow-up of Behçet's disease are based on clinical symptoms, there are no laboratory tests that are widely accepted and utilized for this purpose. Numerous studies have been made to identify possible biomarkers of disease activity and specific organ involvement, however, there is still a need for new biomarkers and more data in this subject. Elafin is a serine protease inhibitor that is constitutively expressed in respiratory, gastrointestinal and genitourinary epithelia and also produced in the skin under inflammatory conditions. It is also known as PI3 (peptidase inhibitor-3) or SKALP (skin-derived antileukoproteinase). An increase in the amount of epidermal elafin has been detected in various skin diseases that are characterized by dermal neutrophilic infiltration, including Behçet's disease. Based on this histopathologic feature, along with the inflammatory nature of Behçet's disease, we hypothesized that there may be a change in the serum elafin levels of patients with Behçet's disease. In our literature search, we could not find any data regarding the relationship between Behçet's disease and serum elafin levels. Therefore, we planned this study to assess the relationship between serum elafin levels and the presence, activity and organ involvement of Behçet's disease. Materials and Methods: This study was planned as a prospective, single-center, observational case-control study. 54 adult patients with Behçet's disease -29 in active and 25 in inactive phase-, diagnosed according to the International Study Group criteria, seen at the Istanbul Medical Faculty Dermatology and Venereology Department, Behçet's Disease Clinic, between May - September 2019 were included in the study. 30 age and sex-matched healthy controls seen in the same period at Istanbul Medical Faculty Dermatology and Venereology Department, General Dermatology Clinic were also included. The participants were questioned regarding their demographic information, known diseases, medications and habits, current and past symptoms. A detailed physical examination was performed. In addition to complete blood count, ESR, CRP, and other routine laboratory investigations, serum elafin levels were measured using the ELISA method. The relationship between serum elafin levels and the activity and various symptoms of Behçet's disease were analyzed. The correlation of serum elafin levels and parameters such as ESR, CRP, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio, which have been suggested to be used in the follow-up of Behçet's disease was assessed. The results were discussed through comparison with existing data in the literature. Results: Mean elafin levels were found to be significantly higher in the Behçet's disease group (1581  469 pg/ml) compared to the control group (1098  283 pg/ml) (p < 0,001). When the participants were grouped as active Behçet's disease, inactive Behçet's disease and control group, mean serum elafin levels were calculated as 1736  492, 1401  376 and 1098  253 respectively, the difference was found to be statistically significant (p < 0,001). Mean elafin levels of patients with current arthritis was found to be significantly high compared to the patients without (1935  609, 1510  409 pg/ml respectively, p = 0,008). Similarly, mean elafin levels of patients with current uveitis was higher than the patients without, however, this was not statistically significant (1903  282 ve 1548  474 pg/ml respectively, p = 0,068). Mucocutaneous symptoms such as oral aphthous ulcers, genital ulcers, and erythema nodosum were found not to be associated with an increase in the serum elafin levels. Through the utilization of an ROC curve, the ideal cut-off to support the diagnosis of Behçet's disease was found to be 1235 pg/ml. Based on this value, the calculated sensitivity of serum elafin levels was %72,2, and specificity was %70,0 for the detection of Behçet's disease. Mean ESR and CRP levels were also found to be correlated with disease activity (p < 0,001). Neutrophil/lymphocyte and platelet/lymphocyte ratio parameters were also found to be correlated with disease activity (p = 0,023, p = 0,010 respectively). Conclusion: Serum elafin levels differ significantly between patients with Behçet's disease and controls, therefore, it may be used as supporting evidence for the diagnosis of Behçet's disease alongside clinical symptoms. Moreover, the difference between the elafin levels of active and inactive stage Behçet's disease suggests it may be used as a marker of disease activity. Especially arthritis and uveitis symptoms cause a bigger rise in the elafin levels. The statistical significance of the association between elafin levels and disease activity seems to be similar to ESR and CRP levels, and stronger than neutrophil/lymphocyte and platelet/lymphocyte ratio. In short, serum elafin measurement seems promising as a potential supportive laboratory test for diagnosing and assessing the activity of Behçet's disease.