Natural autoantibodies and complement promote the uptake of a self antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4(+) T cells in healthy individuals.

Serum from normal individuals contains substantial amounts of natural antibodies (NA) capable of recognizing self antigens. However, the physiological implications of this autoreactivity remain unclear. We have examined the role of self-reactive NA and complement in mediating the uptake of human thyroglobulin (Tg) by human peripheral B cells in reconstituted whole blood. Significant binding of fluorescein isothiocyanate-conjugated-Tg to B cells was observed, and absorption of Tg-reactive antibodies from serum markedly reduced this uptake, as did inactivation of serum complement or blockade of complement receptor types 1 (CR1, CD35) and 2 (CR2, CD21). T cell responsiveness to Tg was examined in a preparation of peripheral blood mononuclear cells (PBMC) cultured in the presence of autologous serum. A subset of CD4(+) T cells exhibited a dose-dependent proliferative response to Tg, which was strongly inhibited by complement inactivation and by immunoabsorption of Tg-reactive antibodies. Furthermore, this T cell response was abrogated by depletion of B cells from the PBMC culture. These data imply that uptake of complement-opsonized Tg / anti-Tg complexes and subsequent presentation of Tg by B cells are prerequisites for the proliferation of Tg-reactive CD4(+) T cells, suggesting a novel role for natural autoantibodies and complement in the regulation of autoreactivity under physiological conditions.

[Screening of school children for familial hypercholesterolemia]. / Screening af skolebørn for familiaer hyperkolesterolaemi.

A total of 3025 families with school children aged six to eight years were offered pilot screening for familial hypercholesterolaemia by measurement of the concentration of apolipoproteins A-1 and B in the children's capillary blood and by analysis of their family histories of early ischaemic heart disease. The concentrations of the apolipoproteins were determined by double rocket immunoelectrophoresis of an eluate of blood spotted on filter paper. Results were available from 2085 children. Because their B:A-1 ratio was above the 97.5 centile and their concentration of B was above the 99th centile, 54 children (2.6%) were selected to have their apolipoprotein concentrations reassessed. The 17 children (0.8%) whose values were persistently above the chosen cut-off points, and all of their available first and second degree relatives, had fasting determinations of serum lipid concentrations carried out. Raised serum concentrations of low density lipoprotein cholesterol and an autosomal dominant pattern of hypercholesterolaemia were found in respectively 12 children and 10 families, suggesting a higher incidence of familial hypercholesterolaemia than the reported 1:500. Further investigations among family members disclosed hypercholesterolaemia in 29 relatives. A family history of early ischaemic heart disease was elicited by questionnaire, and was positive in only five of the 12 school children with hypercholesterolaemia. We conclude that analysis of apolipoproteins from capillary blood spotted on filter paper is suitable for screening for familial hypercholesterolaemia, and that this method is more efficient than screening based on family history.