No abstract

Several lines of evidence implicate the Cytotoxic T Lymphocyte Antigen 4 (CTLA4) gene in susceptibility to autoimmune disease. We have examined the association of systemic lupus erythematosus (SLE) with polymorhisms within the CTLA4 gene that were previously proposed to regulate CTLA-4 function: a single nucleotide polymorphism (SNP) in position þ 49 of exon 1 and a dinucleotide repeat in the 3 0 untranslated region (3'UTR). The 3 0 UTR repeat showed a significant association with SLE, with one allele conferring susceptibility and another conferring protection to the disease. The associated alleles do not support previous suggestions of an allele size-dependent effect of the 3' UTR polymorphism in autoimmunity development and instead suggest that it is in linkage disequilibrium with a true causative locus. No association of the exon 1 SNP with SLE was found in our population. Given the conflicting results obtained in different studies on the association of SLE with this polymorphism, we performed a meta-analysis including seven previously published studies and the present one. Significantly increased and decreased risks for SLE were found for carriers of the G allele and the A allele, respectively. The functional characterization of disease-associated CTLA4 gene variants is now required to elucidate their role in the pathogenesis of SLE and other autoimmune diseases.

Infective endocarditis (IE) is due to a microbial infection of the heart valves or of the endocardium in close proximity to either congenital or acquired cardiac defects. This infection is associated with a high risk of complications. Rheumatic manifestations are known to be frequent complications of IE. Controversy, however, frequently exists about the actual incidence of these complications. This may be due to the small number of series describing the frequency and type of rheumatic manifestations, the absence of uniform criteria used for the diagnosis of IE, and the fact that some studies on rheumatic manifestations in IE have been described from tertiary referral centers, which implicates associated problems of referral bias and uncertainty of denominator population. To investigate further the incidence, clinical spectrum, and outcome of patients with IE and rheumatic manifestations, we examined the features of patients diagnosed with clinically definite IE according to the Duke classification criteria at the single reference hospital for a defined population in northwestern Spain during a 12-year period. Between 1987 and 1998, 100 consecutive patients had 110 episodes of clinically definite IE. Rheumatic manifestations were observed in 46 of the 110 episodes (41.8%). As in other western countries, they occurred more commonly in men aged in their 50s. The most frequent valve involved was the aortic (43.5%) followed by the mitral valve (30.4%). Myalgia was a frequent symptom. Peripheral arthritis, generally as monoarthritis, was clinically evident in 15 cases (13.6%), and sacroiliitis in 1 patient. Low back pain was described in 14 cases (12.7%). Septic discitis was observed in 2 cases, and biopsy-proved cutaneous leukocytoclastic vasculitis was found in 4 cases. Other conditions such as trochanteric bursitis and polymyalgia were observed in 2 and 1 case, respectively. Apart from a significantly higher frequency of hematuria and a trend to lower serum complement levels in patients with rheumatic complications, no differences in clinical features, laboratory tests, or microbiologic blood culture results were found between cases with IE with or without rheumatic manifestations. Also, although patients with rheumatic manifestations had more embolic complications, the inhospital mortality rate in patients with rheumatic manifestations was not significantly different from that of the rest of the patients. The present study supports the claim that rheumatic complications are frequent in patients with clinically definite IE from southern Europe. The presence of musculoskeletal or vasculitic manifestations may be of some help, as warning signs, for the recognition of patients with severe disease who require rapid diagnosis and therapy.