Tumor necrosis factor-alpha and X-linked adrenoleukodystrophy.
The two most common forms of X-linked adrenoleukodystrophy (X-ALD), the childhood cerebral form (CCER) and the adult form, adrenomyeloneuropathy (AMN), arise from the same mutations in the X-ALD gene at Xq28. These two forms are distinguished by the degree of cerebral inflammation. Segregation analysis suggests that an autosomal modifying gene may be a major determinant of phenotype in X-ALD. Thus, a modifying gene could be involved in initiating or promoting the inflammatory response. In this study we detected a difference in tumor necrosis factor-alpha (TNF-alpha) bioactivity, but not TNF-alpha protein levels, in serum from some advanced CCER patients. Early-stage CCER patients and AMN patients were in the normal range. Allelic differences in TNF-alpha or levels of soluble TNF receptor did not account for bioactivity differences or phenotypic heterogeneity in X-ALD.
McGuinness
M C
MC
Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Griffin
D E
DE
Raymond
G V
GV
Washington
C A
CA
Moser
H W
HW
Smith
K D
KD
D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000503:physiopathology*; D000483:Alleles; D001483:Base Sequence; D002648:Child; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007438:Introns; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D018807:Polymorphism, Single-Stranded Conformational; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017931:DNA Primers; D018076:DNA, Complementary; D007375:Interleukin-1; D010835:Phytohemagglutinins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha