Activation of the alternative complement pathway in systemic lupus erythematosus

Area of Science:

• Immunology
• Complement System Biology
• Rheumatology

Background:

• Systemic lupus erythematosus (SLE) involves complex immune dysregulation.
• The complement system, particularly the alternative pathway, plays a role in SLE pathogenesis.
• Previous studies suggested complement activation in SLE, but in vivo alternative pathway involvement needed clarification.

Purpose of the Study:

• To investigate in vitro and in vivo activation of the alternative complement pathway in patients with SLE.
• To correlate alternative pathway activation with clinical manifestations and disease activity in SLE.
• To determine if alternative pathway activation is specific to lupus nephritis or also present in extra-renal SLE.

Main Methods:

• Assessed in vitro alternative pathway activation using sensitized erythrocytes and complement component conversion (C3, factor B) under specific buffer conditions (EGTA/MgCl2).
• Quantified in vivo alternative pathway activation by measuring the fractional catabolic rate (FCR) of radioiodinated (125I) factor B in SLE patients and controls.
• Correlated laboratory findings with clinical data, including disease localization (skin, joints, nephritis) and remission status.

Main Results:

• Six of eleven SLE patients demonstrated in vitro alternative pathway activation.
• All six patients with in vitro activation showed in vivo evidence of alternative pathway activation (increased factor B FCR).
• Two additional patients without demonstrable in vitro activating factors also had elevated factor B FCR, suggesting broader in vivo activation.

Conclusions:

• A significant proportion of SLE patients, including those with mild disease, exhibit evidence of alternative complement pathway activation.
• This activation is not confined to patients with lupus nephritis and may be implicated in extra-renal manifestations of SLE.
• Findings highlight the potential role of the alternative pathway in SLE pathogenesis and suggest it as a therapeutic target.