АНАЛИЗ АКТИВНОСТИ СИГНАЛЬНОГО ПУТИ ИНТЕРФЕРОНА-I У ДЕТЕЙ С СИСТЕМНОЙ КРАСНОЙ ВОЛЧАНКОЙ: РЕЗУЛЬТАТЫ ПИЛОТНОГО ПРОСПЕКТИВНОГО ИССЛЕДОВАНИЯ

Abstract

The interferon system (IFN) is a group of signaling molecules with antiviral, antitumor and antiproliferative effects. The most studied signaling pathway is mediated by IFN type I. Mutations of IFN-I-regulated genes are involved in the pathogenesis of systemic lupus erythematosus (SLE). Interferon index (IFN-I-index) – a quantitative indicator of the level of expression of IFN-Iregulated genes – is used to assess the activity of the interferon system. Objective of the study: to assess the level of the IFN-I index in children with SLE, as well as to compare the clinical and laboratory characteristics of patients with high and normal levels of the IFN-I-index. Materials and methods of research: 40 patients (girls – 83%, boys – 17%) under 18 years of age with SLE diagnosed in accordance to the SLICC 2012 criteria were included in a multicenter prospective open uncontrolled nonrandomized continuous study. The age of the patients was 15,2 (12,5 ; 16,7) years. All of them underwent examination and treatment in the Pediatric department № 3 at the clinic of the St. Petersburg State Pediatric Medical University and in the Pediatric department of the Almazov National Medical Research Center. The IFN-I index was determined by real-time PCR with a quantitative assessment of the expression of 5 genes induced by IFN-α and β. Results: aggravated family history of rheumatic diseases was noted in 8 patients: SLE – in 3 (8%), rheumatoid arthritis – in 3 (8%), cold urticaria – in 2 (5%). The average age of onset of the disease is 12 years. The most common clinical manifestations were lesions of the skin, joints, mucous membranes, central nervous system, kidney and fever. 31 patients (78%) had an increased IFN-I index. All cases of kidney failure were observed only in patients with a high IFN index (36% vs 0%, p=0,036). Patients with increased IFN-I-index had statistically significant increased levels of antinuclear (87% vs 56%, p=0,043) and rheumatoid factors (36% vs 0%, p=0,036), higher ECLAM index values (3,0 vs 1.0, p=0,048), ferritin levels (p=0,0008) and, as a consequence, the need for more intensive immunosuppressive therapy (using rituximab and cyclophosphamide) compared with patients with normal IFN-Iindex. A positive statistically significant correlation of the IFN-I index with male sex (r=0,41, p=0,008), nephritis (r=0,35, p=0,026), livedoid rash (r=0,38, p=0,017 ), Raynaud's phenomenon (r=0,37, p=0,018), high antinuclear factor (r=0,82, p=0,001), rheumatoid factor (r=0,654, p=0,011), antibodies to Sm antigen (r=0,57, p=0,034), as well as a negative relationship with anemia (r=–0,67, p=0,009). Conclusion: IFN-I-index can be considered as a surrogate biomarker of activity and prognosis of SLE. Further research is required to validate its diagnostic role.