Genetically Determined TNF-α Secretion Influences the Development of Dermatomyositis and Systemic Lupus Erythematosus.

BACKGROUND: Abnormal secretion of TNF-α is known to play a role in the pathogenesis of dermatomyositis and systemic lupus erythematosus. MATERIALS AND METHODS: In the present study we have analyzed the concentrations of TNF-α in the sera of 30 patients with systemic lupus erythematosus (SLE), 28 with dermatomyositis (DM) and 30 healthy controls by standard ELISA tests. RESULTS: We have found that -308A allele increases TNF-α secretion, while -1031C and -863A alleles decrease it. The -857C/T and 489G/A polymorphisms appeared in strong linkage disequilibrium (D'=0.93) but they did not seem to affect TNF-α secretion. CONCLUSION: TNF-α polymorphisms play a significant role in its secretion and influence the development of DM and SLE.

Antiphospholipid antibodies in patients with upper-extremity deep vein thrombosis.

The levels of antibodies to cardiolipin and ß2-glycoprotein I and polymorphic variants G1691A of Factor V (factor V Leiden, FVL) and G20210A of prothrombin gene (G20210A) were studied in 16 patients with upper-extremity deep vein thrombosis (UEDVT). Most of patients with this syndrome have elevated values of these antibodies. Two of these patients are heterozygous carriers for G20210A and 1 - for FVL. Three patients with UEDVT and systemic lupus erythematosus (SLE) are positive for ANA and two others (one of them with Raynaud syndrome) have border line titre 1: 80 for ANA. All 3 patients with SLE are women and the interval between the development of the UEDVT and the onset of SLE was 1-4 years. We would like to suggest that: 1) UEDVT could be the first clinical symptom of Antiphospholipid syndrome, and 2) UEDVT may be the first clinical manifestation of SLE preceding the development of the systemic autoimmune disease by several years.

Screening for point mutations in the LDL receptor gene in Bulgarian patients with severe hypercholesterolemia.

Familial hypercholesterolemia (FH) is a common, autosomal dominant disorder of lipid metabolism, caused by defects in the receptor-mediated uptake of LDL (low-density lipoproteins) due to mutations in the LDL receptor gene ( LDLR). Mutations underlying FH in Bulgaria are largely unknown. The aim of the present study was to provide information about the spectrum of point mutations in LDLR in a sample of 45 Bulgarian patients with severe hypercholesterolemia. Exons 3, 4, 6, 8, 9, and 14, previously shown to be mutational hot spots in LDLR, were screened using PCR-single-strand conformation polymorphism (SSCP). Samples with abnormal SSCP patterns were sequenced. Three different, hitherto undescribed point mutations (367T>A, 377T>A, 917C>A) and two previously described mutations (858C>A and 1301C>T) in eight unrelated patients were identified; four of the detected point mutations being missense mutations and one, a nonsense mutation. One of the newly described point mutations (917C>A) is a base substitution at a nucleotide position, at which two other different base substitutions have already been reported. Thus, all three possible base substitutions at this nucleotide position have been detected, making it a hot spot for point mutations causing FH. This is the first such mutational hot spot described in exon 6 of LDLR.