A.M.Georgiadou, MD, MSc
Hippokration General Hospital of Thessaloniki-2nd Department of Internal Medicine-Clinical Immunology Laboratory
Scholar of the General Secretariat for Research and Technology (GSRT) and the Hellenic Foundation for Research and Innovation (HFRI)
Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus (SLE), affecting renal and overall survival as well as quality of life. Despite progress in therapy, up to 10% of LN patients still reach end stage renal disease (ESRD) within 10 years of diagnosis. Complement contribution to LN development and progression is being extensively studied in an effort to gain deeper understanding of the disease, hence new tools for disease monitoring, targeted therapeutic interventions and, hopefully, better outcomes.
Complement system plays an important, yet dual, role in SLE and LN in particular. Its protective effects comprise to the removal of apoptotic materials and immunocomplexes (ICs) and the maintenance of self-tolerance. However, when break of tolerance occurs and ICs start to form (type II hypersensitivity) or deposit (type III hypersensitivity) in the renal tissue, complement becomes part of the mechanism of renal tissue damage and its presence is verified with immunohistochemical staining of renal biopsies.
Complement serves also as serum biomarker for LN, reflecting disease activity. Lower C3 and C4 levels are present in LN patients compared to non renal SLE patients. Their sensitivity and specificity is average, but their negative predictive value for renal flares is more than 90%.
The cornerstone drug for SLE, hydroxychloroquine, affects complement activation by inhibiting the binding of C1q, which is not only the first step for the classical pathway activation, but also an important step for the generation of C3 convertase. More specific complement system biomarkers and new drugs targeting the complement system or its regulators are on trial for LN patients.