Rethinking the red wolf disease: does Protein S suppress systemic lupus erythematosus clinical activity?

Gregg J Silverman

doi:10.1186/ar3162

Abstract

In systemic lupus erythematosus, the forces responsible for disease initiation and self-perpetuation in these clinically heterogeneous populations remain poorly understood. Recent studies of the TAM (Tyro3, Axl and MerTK) family of receptor tyrosine kinases may lead to a better understanding of the fundamental control system responsible for the clearance of apoptotic cells and the regulation of inflammation. In a recent report, serum levels of the TAM ligand, Protein S, was found to correlate with certain disease manifestations and with C3 and C4 levels. Protein S levels could provide a quantitative clinical biomarker but it remains to be determined whether this factor directly affects disease activity.

Highlights

Systemic lupus erythematosus (SLE) is the prototypic chronic inflammatory systemic autoimmune disease, but many aspects of its pathogenesis remain poorly understood
The studies from Cohen and coworkers [1] highlight a new perspective on how breaches in regulatory control of a fundamental homeostatic anti-inflammatory pathway, which first arose far before the mammalian adaptive immune system, may be a major determinant of SLE clinical manifestations and/or local activity
It may not be surprising that the involvement of some but not all organ systems was associated with lower free Protein S levels, as the contributions of infiltrating Mφ and dendritic cell (DC), or other pathways affected by the TAM system, may vary greatly in different affected anatomic sites

Summary

Introduction

Introduction Systemic lupus erythematosus (SLE) is the prototypic chronic inflammatory systemic autoimmune disease, but many aspects of its pathogenesis remain poorly understood. Conditions associated with defects in phagocytic clearance of dead and dying host cells, and especially C1q and IgM deficiency states, may lead to lupus-like disease [2]. These associated clearance defects may result in cellular progression to secondary necrosis and the release of self-ligands (such as High-mobility group protein B1 (HMGB-1) and heat shock protein (HSP)) for inflammatory innate receptors and of self-antigens that drive stimulation and selection of autoreactive lymphocytes.

Results

Conclusion