DR3 and nonDR3 associated complement component C4A deficiency in systemic lupus erythematosus

Area of Science:

• Immunogenetics
• Molecular Biology
• Rheumatology

Background:

• Complement component C4A deficiency is linked to systemic lupus erythematosus (SLE).
• Previous studies suggest gene deletion as a cause of C4A deficiency.
• The genetic basis for C4A deficiency in certain SLE patient groups remains unclear.

Purpose of the Study:

• To investigate the molecular basis of C4A deficiency in U.S. and Mexican SLE patients.
• To determine if C4A gene deletion or gene conversion explains C4A deficiency in non-DR3 SLE patients.

Main Methods:

• Genomic DNA analysis using restriction fragment length polymorphism (RFLP) with HindIII and a C4 cDNA probe.
• Polymerase chain reaction (PCR) amplification of the C4d gene region followed by Nla IV digestion and RFLP analysis.
• Analysis of C4A gene deletion and isotype-specific gene conversion.

Main Results:

• C4A gene deletion was identified in SLE patients with HLA-B8;DR3 and C4A protein deficiency.
• This deletion did not account for C4A deficiency in all non-DR3 Mexican or some U.S. SLE patients.
• No evidence of C4A gene conversion encoding a C4B-like protein was found in non-DR3 SLE patients without C4A gene deletion.

Conclusions:

• C4A gene deletion is associated with C4A deficiency in specific SLE patient subgroups (HLA-B8;DR3 positive).
• C4A gene deletion and gene conversion do not explain C4A deficiency in all non-DR3 SLE patients.
• The molecular basis of C4A deficiency in non-DR3 SLE patients without C4A gene deletion requires further investigation.