C1qrs292001 polymorphism and C1q antibodies in juvenile lupus and their relation to lupus nephritis

Abstract

SummaryC1q deficiency is related strongly to systemic lupus erythematosus (SLE), but very few and inconsistent studies explored the single nucleotide polymorphisms of the C1q gene in relation to juvenile SLE (jSLE) and lupus nephritis (LN). The objective of this study was to analyse whether C1q rs 292001 polymorphism is associated with SLE and disease phenotype, especially nephritis, and to investigate the relation between this polymorphism and clinical data, treatment outcome, serum level of C1q protein and antibodies. Typing of C1q rs292001 polymorphism using restriction fragment length polymorphism and measuring serum levels of C1q protein and antibodies by enzyme-linked immunosorbent assay (ELISA) were performed for 130 children with SLE and 208 healthy controls. The A allele of C1q rs292001 was associated with jSLE and LN (P 5 0Á005 and 0Á013, respectively) and the AA genotype was associated with jSLE (P 5 0Á036). Low serum levels of C1q protein were found in jSLE and LN (P < 0Á001 and 0Á009, respectively), and these levels were increased after treatment in patients with LN (P 5 0Á009) and active renal disease (P 5 0Á027). Higher titres of C1q antibodies were found in patients with LN (P 5 0Á015) and correlated negatively with C1q protein level (P < 0Á001) and patient age (P 5 0Á04). The A allele and AA genotype of C1q rs292001 can be considered a susceptibility risk factor and the GG genotype could be considered protective for jSLE and LN in the studied cohort of Egyptian children. Decreased serum levels of C1q protein and increased titres of C1q antibodies may be involved in the pathogenesis of jSLE, especially LN.

Novel biomarkers for the assessment of paediatric systemic lupus erythematosus nephritis

“…Although a relation between high serum anti‐C1q levels and the presence of pLN, especially in its active state, has been proposed by several researchers, in the present study this relation was not confirmed . The serum anti‐C1q levels did not differ significantly between the pSLE patients with pLN and those without renal involvement.…”

Autoantibodies in SLE: Specificities, Isotypes and Receptors

“…C1q deficiency has been described as a high risk factor to develop SLE [139] but the genetically C1q deficiency in SLE is very rare [140] and the susceptibility risk of gene variants at the C1Q gene remains controversial [141,142]. Conversely, low levels of C1q are typically associated with disease flares and with the appearance of anti-C1q antibodies [80] which, in turn, are found in 20%–50% of SLE patients and in up to 100% of active proliferative LN patients [81].…”

Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype

“…By evaluating 300 South Indian Tamil SLE patients, the authors identified a significantly higher frequency of heterozygous genotype of Q222R polymorphism in patients with nephritis than in those without (67% versus 53%, OR = 1.93) [ 39 ]. Some interesting data concerning the association between LN development and polymorphism on the gene codifying C1q have been recently published [ 41 , 42 ]. However, due to the small cohorts evaluated in these studies, their results should be confirmed in large populations.…”