The first Icelandic family with X-linked agammaglobulinaemia: studies of genetic markers and immune function

Abstract

This paper describes studies of genetic markers and immune functions in the first Icelandic family identified with X-linked agammaglobulinaemia (X-LA), including three affected brothers. The eldest brother was diagnosed at the age of 9 in 1963. He suffered repeated infections and died at the age of 23. The other two affected brothers, diagnosed at 6 years and 1 year of age, are alive and well on immunoglobulin replacement therapy at the ages of 32 and 24. All were typed for HLA, complement, and various other markers. Pedigree analysis suggests an X-linked segregation of the disease. Their serum IgG is maintained at normal levels on therapy. Several parameters of immune function were studied. The following results were obtained for the X-LA brothers: B cells are absent in their peripheral blood samples. T-cell numbers are normal, but monocytes are increased in numbers and activity. No immunoglobulin production could be elicited in vitro with PWM and no cells containing cytoplasmic Ig were detectable among PWM-stimulated blasts. Nevertheless the proliferative response was particularly vigorous, but the responding cells were shown to be exclusively T cells. No blast transformation could be achieved with EB virus. NK-cell activity was normal/high normal. Other cell-mediated immune functions were normal. In conclusion our data indicate that the differentiation of B cells is blocked in the two surviving X-LA brothers. They have survived for a longer time and in better health than is generally reported. Early diagnosis and adequate replacement treatment with Ig is clearly crucial. Vigorous non-specific immune mechanisms may help to compensate for the defective specific immunity.