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A sensitive three-layer solid phase immunoradiometric assay for estimating thyroglobulin antibodies in different mouse immunoglobulin subclasses was established and applied to study the subclass distribution of these antibodies in strains of mice differing in their susceptibility to the development of experimental autoimmune thyroiditis. Low response could not be ascribed to failure to produce a particular subclass. However, the absolute antibody levels in susceptible strains tended to be much higher, particularly in the IgG1, IgG2a and IgG2b classes 2 weeks after immunization. These differences in IgG1 and IgG2a persisted for a further 5 weeks but were less marked in the other subclasses. It would appear that antibody levels may be important in pathogenesis but since mice with high titres of thyroglobulin antibodies do not invariably develop thyroiditis, it is likely that further factors may be involved.

IgG molecules were found associated with erythrocyte membranes in all patients with American visceral leishmaniasis. They were detected by two different immunoradiometric assays and by one enzyme-linked immunosorbent assay. Although autoimmune phenomena seem to be constant features of American visceral leishmaniasis, the erythrocyte-bound IgG are not erythrocyte-specific autoantibodies. Moreover, anti-Leishmania activity was found associated with the erythrocyte-bound IgG, indicating that the IgG may be a component of Leishmania antigens-anti-Leishmania immune complexes. No associations were found between the amounts of erythrocyte-bound IgG and the degree of anaemia or between spleen dimensions and the degree of anaemia. These findings suggest that the pathogenesis of anaemia in American visceral leishmaniasis is multifactorial.

Bloodstream trypomastigotes (BTry) of Trypanosoma cruzi were found to bind to their surface membrane in-vitro fragments of C3, namely C3b and/or C3bi. Different reagents specific for C3 were used: anti-C3c serum and anti-C3 monoclonal antibodies; bovine conglutinine and yeast particles. The BTry, isolated from acutely infected mice and maintained on a complement-free culture medium (TC-199), were strongly agglutinated by these reagents or formed clumps with the yeast only after being previously treated with fresh or heat inactivated normal human serum. It is suggested that the binding of C3b fragments to the parasite membrane may influence the extent or the nature of the early events during T. cruzi infection allowing the BTry to escape complement destruction by the alternative complement pathway.

Fragments of thyroglobulin containing the autoreactive epitopes were prepared by an existing procedure, plus an ion-exchange chromatography step which increased their purity. Before purification, 39% of the fragmental material was bound by rabbit anti-human thyroglobulin whereas only 8% was bound by autoantibody, thus confirming earlier reports of more limited epitopes for human autoantibodies than heterologous antibody. Thyroglobulin autoantibodies in the globulin fractions from six human sera showed between 70 and 100% cross-reaction with one another, indicating that the majority of antibodies are directed against the same epitopes. The data are consistent with an estimated of two distinct major epitopic specificities with occasional sera having antibodies directed against a third site. Chemical modification of tyrosine residues by iodination did not inhibit the binding of thyroglobulin to either human autoantibodies or rabbit anti-human thyroglobulin; thus tyrosine residues do not contribute significantly to the epitopes for either auto- or heteroantibodies.

In addition to thyroglobulin autoantibodies, some Obese strain (OS) chickens gave organ-specific reactions with the cytoplasm of thyroid acinar cells when the sera were tested by immunofluorescence. The staining pattern was similar to that seen with human antibodies to thyroid microsomes. A proportion stained the proventricular glands of the chicken stomach in a manner indistinguishable from that of pernicious anaemia sera containing parietal cell antibodies. Isolated examples of organ-specific reactions with adrenal and exocrine pancreas were also recorded. These findings strengthen the notion that the OS chicken represents an authentic model for human organ-specific autoimmune disease. The high incidence of non-organ specific reactions complicates but does not necessarily invalidate this view since normal chickens show a propensity to develop such antibodies. However the OS chicken appears to differ from the human in being hyper-responsive to antigens in general.