Alternative complement pathway activation in thrombotic microangiopathy associated with lupus nephritis

Area of Science:

• Nephrology
• Immunology
• Rheumatology

Background:

• Thrombotic microangiopathy (TMA) is a rare systemic lupus erythematosus (SLE) complication.
• TMA in SLE is associated with complement system activation.
• Lupus nephritis (LN) involves immune complex deposition and complement activation.

Purpose of the Study:

• To compare plasma and urine complement activation products in active lupus nephritis (aLN) versus acute TMA with active LN (aTMA+aLN).
• To investigate the role of complement pathways in TMA associated with LN.

Main Methods:

• Collected plasma and urine from patients with aTMA+aLN, aLN, chronic TMA, inactive LN, and kidney donors.
• Measured complement fragments (C3a, C4a, C4d, Ba, C5a, C5bC9, factor H) via ELISA.
• Assessed kidney C4d deposition using immunohistochemistry and followed patients for >12 months.

Main Results:

• Both aTMA+aLN and aLN groups showed increased circulating C3a, Ba, C5bC9 and decreased C3, C4, C4a, C4d, factor H.
• Urinary C3a, C5a, Ba, C5bC9 were higher in aTMA+aLN than aLN.
• Treatment decreased urinary complement activation products and increased circulating levels in aTMA+aLN patients.

Conclusions:

• Circulating and urinary complement activation products suggest the alternative pathway mediates TMA in LN.
• C4d deposition is not specific for renal TMA in SLE, appearing in both immune complex nephritis and TMA.
• Understanding complement activation aids in diagnosing and managing TMA in lupus nephritis.