ABERRANT PATTERNS OF IMMUNOGLOBULIN LEVELS IN WISKOTT-ALDRICH SYNDROME

We have investigated IgM deficiency in Wiskott-Aldrich syndrome patien ts. From the assessment of T and B cell functions in pokeweed mitogen- induced immunoglobulin (Ig) production, IgM deficiency was chiefly tho ught to result from B cell dysfunction. The percentages of surface IgM -bearing cells were decreased in peripheral blood mononuclear cells (P BMCs) and the number of IgM-secreting cells was also decreased. Lympho blast cell lines (LCLs) from the patients have produced IgG and IgA, b ut never IgM. Moreover the expression of the C mu transcript from the patients' PBMCs and their LCLs were decreased, whereas the C gamma gen e was well expressed. No germ-line polymorphism existed between the pa tients and the controls in the C mu region, and no mutation was detect ed in the mu s C-terminal and the M exon by nucleotide sequencing. The se suggest that the Ig heavy chain (IGHC) isotype switch may be abnorm ally accelerated in the patients' B cells. While the methylation patte rns of the human Ig enhancer gene region were the same between the pat ient and the control, the methylation patterns of the I gamma 1 region showed less methylation in the patient than in the control, which may cause low IgM expression and high expression levels of other classes located downstream of the IGHC gene.