Chorea-acanthocytosis with polyclonal antibodies to ganglioside GM1.

A patient with chorea-acanthocytosis presenting with axonal neuropathy showed an elevation in IgM polyclonal antibodies to the GM1 ganglioside, which were estimated by enzyme-linked immunosorbent assay and complement-mediated liposome immune lysis assay (LILA). This is the first demonstration of such antibodies in chorea-acanthocytosis. Anti-GM1 antibodies might have directly caused the axonal neuropathy by binding to GM1 or cross-reactive antigens in the nerves.

Analysis of the McLeod syndrome gene in three patients with neuroacanthocytosis.

McLeod syndrome is a rare X-linked disorder involving neurological defects and acanthocytosis. We examined the XK gene in three patients with neuroacanthocytosis, one of whom had cardiomyopathy, and his symptoms were very similar to those of McLeod syndrome. We found two new transversions (C to G at codon 204 and G to C at codon 205) in exon 3 in all those cases. However, the transversion at codon 205 was found in all 70 Japanese normal subjects and four non-Japanese (two Caucasian males, one Chinese female and one Micronesian female) and that at codon 204 was also detected in all 14 normal Japanese males and the four non-Japanese. These findings suggest that they are not the cause of McLeod syndrome, but normal polymorphisms which have not been reported. Moreover, there is a possibility that patients with neuroacanthocytosis similar to McLeod syndrome exist without the XK gene abnormalities.

Membrane channel protein abnormalities and autoantibodies in neurological disease.

Immunological analogues of band 3, the anion transporter of the human erythrocyte, have been identified in all cells, including both isolated neurons and neurons of the central nervous system. We hypothesized that the anion channel is altered in neurological disease associated with choreiform movements because gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, binds to its receptor and opens an integral membrane chloride channel. In order to examine this hypothesis, we studied a family with a serious, progressive, genetic neurologic disorder with acanthocytosis (choreoacanthocytosis) that resembles Huntington's chorea. We selected choreoacanthocytosis because erythrocytes, which are readily obtained, are affected in this disease as well as the central nervous system. Biochemical studies of erythrocytes from the proposita, mother, and brother revealed that sulfate transport Vmax was increased, and glucose efflux was decreased. Erythrocytes exhibited immunological changes indicative of cellular aging/transporter damage. In addition, transporter reactive antibodies were present. This is the first evidence for abnormalities of membrane transport in this neurologic disorder.

Anti-Km in a transfused man with McLeod syndrome.

An 18 year old man has red cells of the McLeod phenotype in the Kell system but does not have chronic granulomatous disease. His red cells show acanthocytic morphology and there is evidence of a compensated hemolytic state. Following an accident he was transfused with blood of common Kell type and made anti-K and anti-Km. Leukocytes from the patient are deficient in Kx antigen but the cells appear to have normal function. The mother is a carrier of the variant Xk allele and has a double red-cell populatio of McLeod cells and cells of common Kell type. The family may be informative with respect to linkage between the Xk and Xg loci. One of the mother's 5 brothers and one of her maternal uncles are possible Xk:Xg recombinants.

Production of epidermal acantholysis in normal human skin in vitro by the IgG fraction from pemphigus serum.

Normal human skin was maintained in organ cultures for several days in Ham's F-10 medium with good preservation of the epidermal cells. When the partially purified IgG fraction from the pooled sera of patients with pemphigus vulgaris or pemphigus foliaceous was added to this culture system, after 24 hr some evidence of epidermal acantholysis was seen. By 72 hr, extensive suprabasilar epidermal acantholysis had occurred in which the acantholytic cells were indistinguishable histologically from the acantholytic cells in biopsies from skin lesions of patients with pemphigus vulgaris. In the control cultures (i.e., F-10 medium or F-10 medium + normal human serum IgG), none of these changes was seen. Direct immunofluorescent staining of these explants using fluorescein-labeled goat antihuman IgG showed that by 6 hr binding of the pemphigus IgG had occurred in the intercellular cement substance of the epidermis. The staining intensity was maximal by 18 to 20 hr. When the pemphigus serum was fractionated by DEAE-cellulose column chromatography, three major IgG-containing peaks (presumably IgG) were eluted which bound to the epidermoid intercellular substance and caused acantholysis in culture. The complement system did not play a role in the antibody-induced acantholysis since complement was not included in this system and heating the reconstituted F-10 + pemphigus IgG for 1 hr at 58 degrees C did not destroy the acantholytic activity. Autoradiographic experiments showed that after about 2 days in culture the rates of incorporation of RNA and protein precursors in the suprabasilar cells in the presence of pemphigus IgG were reduced to less than 10% of the normal IgG controls, whereas these synthetic activities of the basal cells were only slightly affected. These observations lead to the proposal that it is the interaction of the pemphigus autoantibody(s) with the suprabasilar epidermal cell which initiates and possibly substains the process(es) of acantholysis.