Tangier disease (TD) was first discovered nearly 40 years ago in two siblings living on Tangier Island. This autosomal co-dominant condition is characterized in the homozygous state by the absence of HDL-cholesterol (HDL-C) from plasma, hepatosplenomegaly, peripheral neuropathy and frequently premature coronary artery disease (CAD). In heterozygotes, HDL-C levels are about one-half those of normal individuals. Impaired cholesterol efflux from macrophages leads to the presence of foam cells throughout the body, which may explain the increased risk of coronary heart disease in some TD families. We report here refining of our previous linkage of the TD gene to a 1-cM region between markers D9S271 and D9S1866 on chromosome 9q31, in which we found the gene encoding human ATP cassette-binding transporter 1 (ABC1). We also found a change in ABC1 expression level on cholesterol loading of phorbol ester-treated THP1 macrophages, substantiating the role of ABC1 in cholesterol efflux. We cloned the full-length cDNA and sequenced the gene in two unrelated families with four TD homozygotes. In the first pedigree, a 1-bp deletion in exon 13, resulting in truncation of the predicted protein to approximately one-fourth of its normal size, co-segregated with the disease phenotype. An in-frame insertion-deletion in exon 12 was found in the second family. Our findings indicate that defects in ABC1, encoding a member of the ABC transporter superfamily, are the cause of TD.

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The efficacy of plasma exchanges (PE) during the course of scleroderma has only been investigated for short periods. The aim of this study was to follow patients over a long enough period to observe the course of the clinical and paraclinical symptoms in the short, medium, and long term. Forty patients, 24 women and 16 men, were treated by PE and observed for 1-3, 3-12 and over 12 months. Immunological, biological and clinical course and any undesirable side effects were evaluated using a detailed questionnaire. Concomitant therapies were reported and most frequently consisted of corticosteroids, colchicine, factor XIII or vasodilators (nifedipine, captopril). The therapeutic effectiveness of PE was assessed on the basis of improvements in cutaneous, digestive, joint, muscular, lung, cardiovascular and renal lesions. Our findings confirmed the effectiveness of short-term PE on scleroderma (52% of the patients improved during the first 3 months). However, this improvement was transient (5% improvement between 3 and 12 months and only 2.5% over 12 months) and limited to the cutaneous and muscular lesions. Thus, PE cannot be recommended for the treatment of progressive systemic sclerosis.