Anti-Nuclear Antibodies Patterns in Patients With Systemic Lupus Erythematosus and Their Correlation With Other Diagnostic Immunological Parameters.

Jamil A Al-Mughales

doi:10.3389/fimmu.2022.850759

Abstract

BackgroundAntinuclear antibodies (ANA) are major immunodiagnostic tools in systemic lupus erythematosus (SLE); however, their clinical and pathogenic roles are not yet elucidated and are a subject of controversy.ObjectivesThe aim of the study is to explore the pathogenic significance of ANA patterns among SLE patients, by analyzing their association with ANA titers, complement levels and other pathogenic immune markers, namely, anti-double-stranded DNA (anti-dsDNA), complements C3 and C4, rheumatoid factor (RF), anticardiolipin antibodies IgG (ACL IgG) and IgM (ACL IgM), Beta-2 Glycoprotein 1 Antibodies (β2-GP) IgG (β2-IgM) and IgM (β2-IgM), and lupus anticoagulant (LA).MethodA comparative cross-sectional study was conducted among 495 SLE patients, who were diagnosed and classified by consultant rheumatologists according to the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 criteria. SLE immunodiagnostic profiles were analyzed including the following parameters: ANA antibody titers and staining patterns, anti-dsDNA, C3 and C4 levels, aCL, and anti-β2-GP and LA.ResultThe most frequently observed ANA patterns were the speckled (52.1%) and homogeneous (35.2%) patterns, while other patterns were rare representing less than 7% of the patients each. ANA titers were highest in patients with mixed pattern followed by the speckled pattern. Of all the investigated patterns, the peripheral pattern showed the most pathogenic immune profile, namely, highest levels of anti-dsDNA, lowest levels of C4, and highest levels of aCL and β2-GP IgG and IgM.ConclusionThis retrospective study showed that speckled followed by homogeneous ANA patterns were predominant accounting for 52.1 and 35.2% of the patients. The ANA pattern showed several associations with other immune markers that are documented to have significant clinical implications in SLE. Peripheral, mixed, and speckled patterns were associated with higher profiles of immune markers indicative of a potential prognostic value of these patterns in SLE.

Highlights

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by flare up phases and others with low disease activity [1]
96% sensitivity and 93% specificity [22]. Considering these observations, findings from the present study show significantly higher antinuclear antibodies (ANA) and anti-dsDNA profiles in the peripheral staining pattern, support the hypothesis that such pattern may be associated with higher disease activity and may be predictive of greater organ damage
The synthetic indication regarding the clinical implications of our findings, combined with the review of the demonstrated and potential pathogenic roles of the different immune markers and antibody isotypes, suggests that SLE patients with peripheral, speckled and mixed ANA staining patterns have a greater likelihood for more severe disease and organ damage

Summary

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by flare up phases and others with low disease activity [1]. More than 180 different self-antigens were discovered to bind autoantibodies in SLE patients, with high heterogeneity and variable expressions between the patients. These autoantibodies mainly target intracellular components in the nucleus, such as single- (ssDNA) and double-stranded (dsDNA) DNA, and histones, and are called antinuclear antibodies (ANA) [5–7]. Such immunological profile brings an odd complexity in understanding the pathophysiology of the disease. Antinuclear antibodies (ANA) are major immunodiagnostic tools in systemic lupus erythematosus (SLE); their clinical and pathogenic roles are not yet elucidated and are a subject of controversy

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