Preclinical lupus

Abstract

Purpose of review 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 pre-classification period of SLE, including clinical and mechanistic observations, and potential avenues for early identification and intervention. Recent findings Although incomplete lupus erythematosus (ILE) involves fewer clinical manifestations than SLE, ILE can cause organ damage and 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 SLICC 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. Summary 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.

Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective

“…These studies support the concept of a gradual chronological disease progression, from a preclinical asymptomatic phase, to incomplete lupus erythematosus, and finally, to complete lupus erythematosus [149]. Clinical and serologic parameters distinguish patients with incomplete lupus from SLE patients, and identification of these parameters is crucial for early management of disease [150–152]. Consequently, tailoring management based on these early identifications has the potential to significantly improve patient outcomes and reduce healthcare costs.…”

Preventing the development of SLE: identifying risk factors and proposing pathways for clinical care

“…144 Of note, ANA positivity is also a highly frequent feature of ILE. 14,16 As in a recently described template and economic analysis, patients who are 'incidentally' found to have a clearly positive ANA (i.e. titer >1:80) should have a complete history and physical exam to evaluate for signs and symptoms of disease, and routine testing for a complete blood count, serum creatinine and liver enzymes as well as a urinalysis, C3, C4 testing, ENA panel, anti-dsDNA and anti-phospholipid antibody screening.…”

“…[6][7][8][9][10] We posit that by understanding published demographic, clinical, biomarker, genetic and environmental features associated with the onset of SLE, an approach may be developed to case finding of early or incomplete lupus erythematosus (ILE) followed by the implementation of evidencebased strategies to avert, delay or ameliorate pathogenic disease processes. [11][12][13][14][15][16][17] The anticipated outcomes of this approach are to achieve an early diagnosis, to initiate appropriate, evidence-based efficacious interventions to improve outcomes and quality of life and decrease health care costs. CSLE, usually within 5 years of disease onset.…”

“…Patients that do transition to CSLE may have accrued some irreversible organ damage by the time of a definitive diagnosis. 16 Organ damage was more common in ILE patients of older age and with high systemic lupus erythematosus disease activity index (SLEDAI) scores. 24 There is a need to identify the patients who are most likely to progress to CSLE and hence target therapy to those who are likely to experience the greatest benefit.…”

Editorial: Subduing Lupus: Can Preclinical Autoimmune Disease Be Arrested?

“…Some knowledge has been gleaned from studying later stages in disease progression, including the state termed undifferentiated connective tissue disease (UCTD) in which some clinical symptoms of connective tissue disease are present, though they are not specific for a distinct clinical entity, or the state termed preclinical, incomplete, or potential lupus in which some specific features of lupus are present but insufficient in number to classify the patient with this disease. From these studies, it can be inferred that female sex, homogenous ANA pattern, certain ANA specificities (anti-dsDNA or anti-Smith), anti-cardiolipin antibodies, multiple autoantibody reactivities, and multiple clinical features of lupus are predictive of transition to clinical lupus [reviewed in (1)]. Another biomarker associated with lupus transition is increased ratios of Th17 cells to regulatory T cells (2), which suggests that skewing in inflammatory and regulatory immune mechanisms promotes disease development.…”