Linkage analysis of candidate myelin genes in familial multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. A complex genetic etiology is thought to underlie susceptibility to this disease. The present study was designed to analyze whether differences in genes that encode myelin proteins influence susceptibility to MS. We performed linkage analysis of MS to markers in chromosomal regions that include the genes encoding myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMGP), and myelin oligodendrocyte glycoprotein (MOG) in a well-characterized population of 65 multiplex MS families consisting of 399 total individuals, 169 affected with MS and 102 affected sibpairs. Physical mapping data permitted placement of MAG and PLP genes on the Genethon genetic map; all other genes were mapped on the Genethon genetic map by linkage analysis. For each gene, at least one marker within the gene and/or two tightly linked flanking markers were analyzed. Marker data analysis employed a combination of genetic trait model-dependent (parametric) and model-independent linkage methods. Results indicate that MAG, MBP, OMGP, and PLP genes do not have a significant genetic effect on susceptibility to MS in this population. As MOG resides within the MHC, a potential role of the MOG gene could not be excluded.

Microsatellite polymorphism in the promoter sequence of the elongation factor 3 gene of Candida albicans as the basis for a typing system.

The polymorphism of a TTC/TTTC microsatellite in the promoter sequence of the elongation factor 3 gene of Candida albicans was investigated by PCR. One primer was fluorescein labeled, and PCR signals were read with an automatic sequencer. Twenty-nine reference strains and 31 independent clinical isolates were studied. Eleven different alleles were identified, giving 16 different profiles among the 60 strains tested, with a discriminatory power of 0.88. This marker is stable upon subculture, and reproducibility was achieved by automated procedures. When several microsatellite markers are available, many isolates can be rapidly and reproducibly tested for epidemiological questions, such as the prevalence of a given strain in a hospital setting and transmission between patients.

Autoantibodies to phospholipids and to the coagulation proteins in AIDS.

In HIV-1 infection, an increased prevalence of anticardiolipin autoantibodies (aCL) and lupus anticoagulant (LA) has been described. In order to see if these antibodies are isolated or, like in autoimmune diseases, associated with hematological disorders and with antibodies to other phospholipids and to proteins of coagulation, we investigated 3 groups of patients: 1. 342 HIV-1 infected patients, 2. 145 control patients including 61 systemic lupus erythematosus (SLE) patients, 58 patients with a connective tissue disease, 15 patients with stroke, 11 patients with syphilis and 3. 100 blood donors. In HIV-1 infection antiprothrombin (aPrT) antibodies were present in 2% of patients, the prevalence of antiphosphatidylcholine antibodies (aPC) (50%) was almost as high as aCL (64%), and 39% had both antibodies. Absorption on liposomes of the latter revealed an heterogeneous mixture of aCL and aPC or cross-reacting antibodies. In contrast with SLE, anti-beta 2-glycoprotein I (4%), LA (1%), biological false positive test for syphilis (0.3%), thrombosis (p < 0.001) were uncommon. In HIV-1 infection, antiphospholipid antibodies do not associated with features linked to them in SLE or syphilis.

Association of antimitochondrial antibodies type 5 and anti-beta 2 glycoprotein I antibodies in the antiphospholipid syndrome.

OBJECTIVE: To evaluate if antimitochondrial type 5 antibodies (AMA5) might be included among antiphospholipid syndrome (APS) markers. METHODS: In a retrospective study, blood variables of 48 patients with AMA5 were analyzed in relationship with clinical and biological markers of APS and systemic lupus erythematosus (SLE). RESULTS: We observed a high prevalence of false biological test for syphilis (95%), lupus anticoagulant (LAC) (71%), anticardiolipin antibodies (aCL) of IgG (71%) and IgM (75%) isotype, positive direct Coombs' test (54%), thrombocytopenia (52%), anti-B2 glycoprotein I antibodies (38%). Twenty-nine patients (61%) had at least one clinical manifestation of APS; 42% had recurrent arterial and/or venous deep thrombosis and 21% had recurrent fetal loss. But, for 2 patients, AMA5 were the sole detected immunological marker. Moreover, SLE was observed in 35% of the patients. These were different from 100 control patients with SLE with the respect to skin involvement and dsDNA antibodies which were less frequent (p < 0.01) and aCL, LAC, false biological test for syphilis (p < 0.001), positive direct Coombs' test and thrombocytopenia (p < 0.05) which were more frequent. CONCLUSION: Our data suggests (1) AMA5 is another marker of the APS (2) in patients with SLE, AMA5 seems to be a marker of a subset of SLE. This appears to justify the routine detection of these antibodies.