Complement activation by antibodies to Sm in systemic lupus erythematosus

Area of Science:

• Immunology
• Biochemistry
• Rheumatology

Background:

• Antibodies to Sm (anti-Sm) are a biomarker for systemic lupus erythematosus (SLE).
• The role of complement activation by anti-Sm in SLE pathogenesis requires further investigation.

Purpose of the Study:

• To develop an enzyme-linked immunosorbent assay (ELISA) for quantifying anti-Sm antibodies.
• To measure the in vitro complement-activating capacity of anti-Sm antibodies.
• To correlate in vitro complement activation by anti-Sm with in vivo complement activation in SLE patients.

Main Methods:

• Developed an ELISA to detect and quantify IgG and IgM anti-Sm antibodies in patient plasma.
• Assayed complement activation by immobilizing purified Sm antigen and incubating with patient plasma and normal human serum.
• Quantified C4 deposition as a measure of complement activation using enzyme-linked antibodies.
• Measured in vivo complement activation using rocket immunoelectrophoresis for C4d and C4.

Main Results:

• Detected anti-Sm antibodies in 12 out of 36 SLE patients.
• All 12 patients with anti-Sm antibodies demonstrated complement activation in vitro.
• Anti-Sm antibodies were predominantly of the IgG class (10/12 patients), with two patients having both IgG and IgM.
• The level of C4 activation by anti-Sm in vitro significantly correlated with in vivo C4 activation markers (C4d and C4).

Conclusions:

• The developed ELISA effectively quantifies anti-Sm antibodies and their complement-activating potential.
• Complement activation by anti-Sm antibodies occurs in a significant subset of SLE patients.
• In vitro complement activation by anti-Sm is relevant in vivo, suggesting a role in SLE pathogenesis.