Clinical significance of interferon status in patients with systemic lupus erythematosus. Preliminary data

Background . Studies of systemic lupus erythematosus (SLE) pathogenesis have identified two major families of mediators: type I interferon (IFN-I) and autoantibodies to nucleic acids and their proteins, as the main factors contributing to the development of the disease. Against a background of genetic predisposition, a trigger stimulus, possibly microbial, induces the production of IFN-I, autoantibodies or, more likely, both, leading to inflammation. The interaction of cells of the innate and adaptive immune system are involved in the autoimmune response with the development of a variety of clinical manifestations of SLE. The aim of our study was to describe clinical and immunological characteristics of systemic lupus erythematosus depending on interferon gene signature (IFNGS). Material and methods This observational retrospective-prospective study included 76 patients (86% women, median aged 33 [25; 43] years (median [interquartile range 25%; 75%]), with a definite diagnosis of SLE (SLICC (Systemic Lupus International Collaborating Clinics), 2012) attending a routine visit at our Clinic between February 2021 and June 2024. Baseline demographics, disease characteristic, organ system involvement/damage were analysed descriptively according to SLE Disease Activity Index 2000 (SLEDAI-2K), SLICC Damage Index (SDI) and IFNGS status (high/low). IFN status was assessed by the expression of IFN-inducible genes ( MX1 , RSAD2 , EPSTI1 ) using real-time polymerase chain reaction. IFNGS was calculated as the average expression value of three selected genes. In patients, IFNGS was considered high when the average value of gene expression exceeded the average value of gene expression in donors. The control group consisted of 20 healthy donors comparable in sex and age with the SLE patients. Results . The median disease duration was 2.3 [0.2; 11.0] years, SLEDAI-2K – 7 [4; 11], SDI – 0 [0; 2]. IFNGS-high was detected in 72% of SLE patients. IFNGS-high patients were younger at the time of inclusion (31 [25; 41] and 40 [32; 49] years, respectively), had less frequent remission of SLE (SLEDAI-2K=0) (2% and 19%, respectively), and higher concentrations of anti-dsDNA (219.8 [120.3; 729.3] and 131.0 [46.6; 265.9] IU/ml, respectively; normal <100 IU/ml), ANF titer ≥1/1280 (84% and 52%, respectively), lower absolute count of blood leukocytes (4.2 [3.2; 5.6] and 6.6 [4.2; 8.8]×10 9 /L, respectively) and lymphocytes (1.3 [0.8; 1.8] and 2.0 [1.2; 3.2]×10 9 /L, respectively; p <0,05 in all cases). Of the criterion and non-criteria manifestations of SLE the greater proportions of IFNGS-high versus IFNGS-low patients had haematological (56% and 29%, respectively), primarily leukopenia (53% and 24%, respectively) and dermal (31% and 19, respectively %) involvement ( p <0,05 in all cases). Conclusions . Elevated type I IFN signalling is a marker of a certain type of SLE patients – young age with predominant skin, haematological and immunological disorders. No association with standard therapy and the expression level of certain IFNGS was found.