LABORATORY BIOMARKERS FOR SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

The development of innovative technologies using mono- and multiplex methods of immune analysis contributed to an increase in the sensitivity and specificity of laboratory tests and a significant expansion of the range of laboratory biomarkers of systemic lupus erythematosus (SLE). The article presents modern aspects of laboratory diagnosis of SLE. Screening and confirmatory methods for the study of antinuclear antibodies (ANA), the main immunological marker of SLE, are considered in detail. New classification criteria for SLE are discussed (EULAR/ACR, 2019), which for the first time single out “seropositivity” for the antinuclear factor as a mandatory “incoming” criterion that allows diagnosing the disease as SLE. The characteristics of clinical and laboratory subtypes of SLE associated with the detection of various autoantibodies in serum (antibodies to dsDNA, histones, nucleosomes, Sm, Ro/SSA and La/SSB, U1 ribonucleoprotein,ribosomal protein P, antiphospholipid antibodies, antibodies to C1q) are given. The diagnostic value of defects in the components of the complement system in SLE is indicated. The relationship between ANA and cytokine profiles in SLE patients using multiplex immunoassay of these biomarkers based on xMAP microarray technology is described. It has been shown that the formation of ANA and high activity of SLE are associated with overexpression of the IP-10 and MCP-1 chemokines induced by IFN. The clinical and pathogenetic significance of subpopulations of B-lymphocytes and CD4+ CD25high+ FoxP3+ regulatory T-cells (Treg) of peripheral blood in SLE was noted. SLE is characterized by an increase in the number of double negative memory B cells (CD19+ CD27-IgD-) and plasma cells, a decrease in the levels of naive and transitional B cells in the blood. A positive correlation was found between the number of double negative B cells and the activity of SLE and ESR. The effect of therapy with genetically engineered biological agents (rituximab and belimumab) on B-cell subpopulations in patients with SLE was analyzed. The decrease in the number of Tregs is most pronounced in patients with an acute variant of the course of the disease, high activity of the pathological process, hyperproduction of IgG and expansion of autoreactive B-cells. The study of modern molecularcellular biomarkers allows diagnosing, assessing activity, the nature of the course, clinical and laboratory subtypes of SLE, and predicting the effectiveness of therapy for this disease at a qualitatively new level.