Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity.

BACKGROUND: Several findings link systemic lupus erythematosus (SLE) with C1q, the first molecule of the classical complement pathway. Polymorphisms of the C1qA gene are associated with low serum C1q levels in patients with cutaneous LE, but C1q polymorphisms have not been studied in patients with systemic lupus. OBJECTIVE: To determine whether polymorphisms of the C1q genes are associated with SLE, disease phenotypes, serum C1q and CH50 levels. METHODS: DNA for genetic analysis was obtained from 103 Caucasian patients with SLE and their family members. Five tag single nucleotide polymorphisms (tag SNPs) served as unique markers for underlying SNPs in the genes of the C1q protein. The pedigree disequilibrium test (PDT) was applied to trios to determine association of markers with SLE, SLE phenotypes, low serum C1q and low CH50. Single SNP association and haplotype analysis was also performed. RESULTS: The PDT revealed a significant association of the tag SNP rs631090 (covering the C1qB gene) with SLE (p = 0.02). Rs631090 was moderately associated with low serum C1q levels (p = 0.06). In addition, the tag SNPs rs292001 and rs294183 were associated with more severe SLE (Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) damage index score>0; p = 0.007 and p = 0.02, respectively). Haplotype analysis and single SNP association analysis showed no significant associations, but additional analyses revealed that marker rs587585 is associated with low serum C1q and CH50 levels. CONCLUSIONS: C1q polymorphisms are associated with SLE, serum C1q and CH50 levels in a stable founder population of patients with SLE. Although the studied population was small and allele frequencies were low, this is the first study to suggest an association of C1q polymorphisms with SLE.

Induction of glial L-CCR mRNA expression in spinal cord and brain in experimental autoimmune encephalomyelitis.

Chemokines and chemokine receptors are important regulators of leukocyte trafficking and immune response. It is well established that chemokines and their receptors are also expressed in the central nervous system (CNS), where their expression has been associated with various neuroinflammatory diseases, such as multiple sclerosis (MS). One of the most important chemokines involved in MS pathology is CCL2 (previously known as MCP-1). CCL2, released by glial cells, activates the chemokine receptor CCR2, causing the infiltration of blood monocytes in tissues affected by MS. There is evidence, however, that CCL2 also has local effects on CNS cells, including induction or modulation of cytokine release and synthesis of matrix metalloproteinases, that might contribute to CNS pathology. These effects are most likely independent of CCR2, since CCR2 expression in glial cells is rarely observed. We have recently provided evidence for the presence of an alternative CCL2 receptor in glial cells called L-CCR and have investigated the expression of L-CCR mRNA in a murine EAE model. It is shown that L-CCR mRNA is expressed in infiltrating macrophages during EAE, but not in infiltrating T cells. Prominent expression of L-CCR mRNA was detected in astrocytes and microglia already at early time points throughout the brain and spinal cord supporting the hypothesis that L-CCR expression in glial cells is related to CNS inflammation.