Molecular characterization of the complement C1q, C2 and C4 genes in Brazilian patients with juvenile systemic lupus erythematosus

OBJECTIVE: To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus. METHODS: Patient 1 (P1) had undetectable C1q, patient 2 (P2) and patient 3 (P3) had decreased C2 and patient 4 (P4) had decreased C4 levels. All exons and non-coding regions of the C1q and C2 genes were sequenced. Mononuclear cells were cultured and stimulated with interferon gamma to evaluate C1q, C2 and C4 mRNA expression by quantitative real-time polymerase chain reaction. RESULTS: C1q sequencing revealed heterozygous silent mutations in the A (c.276 A>G Gly) and C (c.126 C>T Pro) chains, as well as a homozygous single-base change in the 3′ non-coding region of the B chain (c*78 A>G). C1qA mRNA expression without interferon was decreased compared with that of healthy controls (p<0.05) and was decreased after stimulation compared with that of non-treated cells. C1qB mRNA expression was decreased compared with that of controls and did not change with stimulation. C1qC mRNA expression was increased compared with that of controls and was even higher after stimulation. P2 and P3 had Type I C2 deficiency (heterozygous 28 bp deletion at exon 6). The C2 mRNA expression in P3 was 23 times lower compared with that of controls and did not change after stimulation. The C4B mRNA expression of P4 was decreased compared with that of controls and increased after stimulation. CONCLUSIONS: Silent mutations and single-base changes in the 3′ non-coding regions may modify mRNA transcription and C1q production. Type I C2 deficiency should be evaluated in JSLE patients with decreased C2 serum levels. Further studies are needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis.