Receptor for advanced glycation end products (RAGE) polymorphisms are associated with systemic lupus erythematosus and disease severity in lupus nephritis.

OBJECTIVE: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. METHODS: For this cross-sectional study DNA samples of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four RAGE polymorphisms: -429 T/C, -374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. RESULTS: The C allele of -429 T/C, the T allele of -374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE -429 T/C, the A allele of -374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. CONCLUSION: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN.

[An infant with facial skin lesions]. / Een zuigeling met huidafwijkingen in het gelaat.

A 42 year old woman was diagnosed with SLE, ANA and anti-SSA antibodies were positive. Her daughter had cutaneous lesions typical of neonatal lupus erythematosus. Children with NLE can also develop cardiac conducting disturbances. These are associated with significant morbidity and mortality, therefore, monitoring is required in patients with anti-SSA antibodies.

[Rheumatoid arthritis: more than a joint disease]. / Reumatoïde artritis: meer dan een gewrichtsziekte.

Rheumatoid arthritis (RA), one of the most common autoimmune disorders, mostly manifests itself as polyarthritis. However, extra-articular organ manifestations can also occur, even though their incidence has decreased substantially due to effective treatment with disease-modifying anti-rheumatic drugs. In this article we describe three patient cases of extra-articular manifestations in RA in the absence of prominent arthritis. The diversity of symptoms in RA can be of interest to different medical specialties who will occasionally encounter them in daily practice.

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.

An extensive screen of the HLA region reveals an independent association of HLA class I and class II with susceptibility for systemic lupus erythematosus.

OBJECTIVES: The association of systemic lupus erythematosus (SLE) with the human leucocyte antigen (HLA) region is well known. In this study, we analysed the involvement of the HLA region in susceptibility for SLE in a stable founder, Caucasian population of SLE patients. METHODS: We performed an extensive screen of the entire HLA region on 103 SLE patients and family-based controls. Both single locus association analysis and haplotype sharing analysis were performed. The Additional Disease Locus Test (ADLT) was applied to examine the nature of the observed associations and to distinguish true causal associations from associations due to linkage disequilibrium (LD). RESULTS: Significant associations were observed at markers in the HLA class I, class II, and class III regions using both haplotype sharing and single locus methods. The haplotype sharing methods revealed the most significant difference at marker D6S1666 in the HLA class II region (p(HSS) = 0.00037, p(CROSS) = 1.7 x 10(-5)). The most significant result for single locus association was shown at marker D6S265 in the HLA class I region (p = 0.00019). The ADLT demonstrated that these markers represent independent associations. CONCLUSION: HLA class I, class II, and class III are associated with SLE, but only class I and class II contribute independently to increased risk of SLE.

Role of CCR5 Delta32 bp deletion in RA and SLE.

CCR5 and its ligands play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A deletion of 32 bp in its gene leads to the production of a non-functional receptor. Although a protective effect of CCR5 Delta32 for the development of RA has been suggested, future study is required to establish the exact role of this deletion for susceptibility to SLE and lupus nephritis. Also, with regard to the association of CCR5 Delta32 with disease severity in RA and SLE, more data are needed to draw firm conclusions. This might become even more relevant as a CCR5 blocking agent is now available.