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Oxidative modification of LDL has been proposed as an early and crucial step in the development of atherosclerosis, and antibodies against such modified LDL are found in both healthy individuals and patients with atherosclerosis. In this study, 62 patients who were surgically treated for peripheral arterial occlusive disease below the age of 50 were investigated and compared with age- and sex-matched healthy individuals in a case-control study. Autoantibodies against oxidized LDL were measured with an enzyme-linked immunosorbent assay method. Risk factors such as smoking, hypertension, family history of premature cardiovascular events, and lipoprotein levels were also determined. The patients had significantly higher levels of autoantibodies against oxidized LDL; significantly higher levels of total cholesterol, LDL cholesterol, triglycerides, and apo A-I; and significantly lower levels of HDL cholesterol than did control subjects. In multivariate analyses autoantibodies against oxidized LDL discriminated better between patients and control subjects than did any of the different lipoprotein analyses. Among patients, the presence of hypertension and a family history of cardiovascular events were the only factors significantly associated with increased levels of autoantibodies against oxidized LDL.

The aim of the present study was to evaluate the role of residual insulin production in long-term Type 1 (insulin-dependent) diabetes mellitus. Ninety-seven patients with a disease duration of 9-16 years and onset before the age of 30 years were studied. C-peptide excretion in 24-h urine samples was measured as an indicator of residual insulin production. Thirty-five patients (36%) excreted C-peptide (greater than or equal to 0.2 nmol); as many as possible of them were carefully matched with a non-excretor patient with regard to age at onset of diabetes and disease duration. Twenty-nine pairs were obtained, and 22 of them agreed to participate in further investigations of glycaemic control and microangiopathic lesions. The patients who excreted C-peptide had significantly lower HbA1c than the non-excretor group, 6.9 +/- 0.3% vs 7.9 +/- 0.3%, (p less than 0.025). Moderate-to-advanced background retinopathy was found in 2 patients in the excretor group and in 7 patients in the non-excretor group. Microalbuminuria [ratio of albumin: creatinine (mg/l:mmol/l) greater than or equal to 5] was found in 1 and in 5 patients, respectively, while proteinuria [ratio of protein: creatinine (mg/l:mmol/l X 10) greater than or equal to 136] was found in 0 and in 4 patients, respectively. Microalbuminuria and/or proteinuria was found in 7 of the non-excretor group as compared to 1 in the excretor group (p = 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract. Wang XB, Pirskanen R, Giscombe R, Lefvert AK (Shanghai University of TCM, Shanghai, China; and Karolinska University Hospital and Karolinska Institutet, Stockholm; Sweden). Two SNPs in the promoter region of the CTLA-4 gene affect binding of transcription factors and are associated with human myasthenia gravis. J Intern Med 2008; 263: 61-69.Objectives. The molecular mechanisms underlying the regulation of the CD152 (CTLA-4) gene are largely unknown. Two single nucleotide polymorphisms (SNPs) located in the promoter region are suspected to contribute to the pathogenesis of myasthenia gravis (MG) through regulation of gene expression.Setting, Subjects and Design. One hundred and sixty-five unrelated Swedish-Caucasian patients with MG (103 females and 62 males, age 17 to 92 years) and 148 ethnically matched healthy individuals were studied. Gene typing of two SNPs (T/C )1772 and A/G )1661 ) and quantification of soluble CD152 were performed in the patients. Besides the association studies, the function of these two SNPs is characterized.Results. We present new genetic associations of two SNPs in the CD152 gene with human MG. These SNPs located in the promoter region are involved in transcriptional binding activity for Nuclear Factor I (NF-1) and c/EBPbeta, as demonstrated using chromatin immunoprecipitation and electromobility shift assay. MG patients with the T/C )1772 polymorphism have elevated levels of sCD152 in sera.Conclusions. The two SNPs in the promoter region are associated with MG and might cause abnormal alternative splicing and affect the expression of CD152, thereby contributing to the pathogenesis of MG.

Ninety-five percent of patients with palmoplantar pustulosis are smokers at onset of the disease. The aim of this study was to determine whether these patients have serum antibodies to nicotinic acetylcholine receptors (nAChR ab) and if their sera induce a specific immunofluorescence in normal palmar skin. Sera from 45 patients with palmoplantar pustulosis and 23 patients with chronic hand eczema were analysed for muscle nAChR ab, and immunofluorescence was performed on healthy palmar skin. Forty-two percent of the patients with palmoplantar pustulosis but none of the eczema patients had raised levels of nAChR ab. Immunofluorescence showed staining on endothelial cells in the papillary dermis in 47% of all sera from patients with palmoplantar pustulosis and in those with nAChR ab in 68%. On palmar skin from smokers there was also a staining of the sweat duct. Sera from patients with chronic hand eczema were negative. Our findings indicate that palmoplantar pustulosis is an autoimmune disease, possibly induced by smoking.

We conclude that a single IVMP treatment is efficacious and safe in the treatment of moderate MG.

SUMMARYImmunoglobulin E has been associated with severe malaria suggesting a regulatory role for interleukin (IL)-4 and/or IgE in the pathogenesis of severe malaria. We have investigated possible associations between polymorphisms in the IL-4 repeat region (intron 3) and promoter regions (IL-4 +33CT and -590CT) in Ghanaian children with severe malaria. There was a significantly higher frequency of IL-4 intron-3 B1B1 genotype in the cerebral malaria group [ P < 0·0001, odds ratio (OR) = 8·7]. The genotype and allele frequencies of the IL-4 -590 and +33 polymorphisms did not differ between the four study groups. Carriers of IL-4 +33T/ -590T with cerebral malaria had elevated total IgE compared to noncarriers ( P = 0·03). Our data suggest that IL-4 and/or IgE play a regulatory role in the pathogenesis of severe or complicated malaria.