Preclinical lupus.

Abstract

Systemic lupus erythematosus (SLE) is often preceded by immune dysregulation and clinical manifestations below the threshold for SLE classification. This review discusses current and evolving concepts about the preclassification period of SLE, including clinical and mechanistic observations, and potential avenues for early identification and intervention. Although incomplete lupus erythematosus (ILE) involves fewer clinical manifestations than SLE, ILE patients can suffer organ damage and early mortality. Common clinical features in ILE include antinuclear antibody seropositivity, polyarthritis, immunologic manifestations, and hematological disorders. Despite having lower disease activity and damage scores than SLE patients, ILE patients may develop pulmonary arterial hypertension, or renal, neurological, or peripheral vascular damage. The recently proposed Systemic Lupus International Collaborating Clinics SLE classification criteria could shift the period considered 'preclinical SLE'. Murine studies suggest that the balance of T-helper/T-regulatory cells, peroxisome proliferator-activated receptor γ activity, and plasmacytoid dendritic cell pathways may be valuable targets for early intervention. Advances in our understanding of early SLE, including stages before clinical features are fully developed, will improve our ability to identify individuals at high risk of classification for potential prevention trials, provide necessary information to improve diagnostic testing, and perhaps identify novel targets for directed therapeutics in clinical SLE.