Nonantigenicity and immunologic tolerance: the role of the carrier in the induction of tolerance to the hapten.

Treatment of adult mice with dinitrophenyl (DNP) bound to isogeneic serum resulted in a specific inability to respond to DNP after challenge with DNP-keyhole limpet hemocyanin (KLH) in complete Freund's adjuvant. The unresponsiveness to the hapten had all the characteristics of immunologic tolerance: it had a definite induction time; it was transient but could be maintained by additional injections of the tolerogen; it was antigen specific and dose dependent. In addition, the induction of tolerance to DNP is dependent on the nature of the carrier. Two main conclusions can be drawn from these data: DNP conjugates of three homopolymers of lysine were found to be nonimmunogenic in mice, yet tolerogenic. Thus, antigenicity is not necessary to induce tolerance. Among the various carriers tested, isogeneic 7S immunoglobulin (IgG) was found to be the most effective to induce and maintain tolerance to the hapten. This suggests that IgG may have a function other than its usual role as an immunoglobulin.

Deletion of hapten-binding cells by a highly radioactive 125-I conjugate.

Exposure of normal mouse spleen cells in vitro to highly (125)I-labeled dinitrophenyl (DNP)-protein carrier conjugates specifically inactivated cells able to mount an immune response to that hapten after in vivo challenge. The deletion was hapten specific and independent of the radioactive carrier to which the hapten was bound. DNP-binding cells were inactivated by radioactivity that was not part of the hapten, but was solely confined to the carrier moiety. The deletion of the anti-DNP response lasted 2-3 wk and could be specifically inhibited.

Shiny spots in the iris in chronic uveitis.

A case of chronic uveitis with shiny spots in the iris is described. Histologically the shiny spots proved to be Russel bodies. The nature of the Russel bodies is discussed.

Spontaneous increase of DNA turnover in murine systemic lupus erythematosus.

DNA synthesis and release was studied in unstimulated splenocytes of strains of mice known to develop spontaneous systemic lupus erythematosus (SLE)-like disease and in non-SLE age- and sex-matched strains as well. Newly synthesized DNA was measured as total acid-insoluble radioactive material present in cell pellet plus supernatant of unstimulated 0-72 h cell cultures [3H]thymidine-pulsed, whereas DNA release was measured as amount of acid-precipitable radioactivity found in supernatant of those cultures. In all strains known to develop spontaneous murine SLE the amount of newly synthesized DNA was 1.3-2.1-fold increased when compared to normal strains studied concomitantly. Furthermore, a significant increase in DNA release into medium, unrelated to cell viability, was observed in those strains as well. These observations clearly demonstrate different metabolic rates of synthesis and release of DNA in murine SLE. This difference suggests the existence of an underlying mechanism responsible for extracellular DNA abundancy, which may be important for the formation of circulating DNA-anti-DNA immune complexes.

Anti-heart autoantibodies in ischaemic heart disease patients.

One hundred and ninety-nine ischaemic heart disease (IHD) patients were studied with regard to the prevalence of anti-heart autoantibodies (AHA). The incidence of AHA in IHD patients was 1%: one out of 102 patients who suffered acute myocardial infarction (AMI), one out of seventy-two patients who suffered from acute coronary insufficiency (ACI), and none out of twenty-five patients with other signs and symptoms of IHD, had AHA in their sera. An additional 2% of patients who suffered from AMI developed detectable antibody levels during a follow-up period of 15 days. In comparison,, 53% of patients (eight out of fifteen) who underwent heart surgery and who had no AHA prior to operation, developed these antibodies in their sera during 1-2 weeks following operation.

Increased photosensitivity to near-ultraviolet light in murine SLE.

We investigated whether there is increased susceptibility to near-UVL in murine SLE. Cultured spleen cells from either strain of mice with lupus disease or conventional strains of mice were exposed to different UVL fractions in vitro. The effect of DNA synthesis, release, and repair was examined. DNA synthesis and release was measured as percent of [3H]thymidine (dT) uptake into either total acid-precipitable radioactive material of cell sediment plus supernatant, or that of the medium alone, whereas hydroxyurea-resistant dT incorporation represented DNA repair. The data indicate that all SLE strains, in contrast to all non-SLE strains, show increased DNA synthesis and release after UV-A exposure. In addition, all murine SLE strains demonstrate increased susceptibility to induction of DNA damage by UV-A. The significance of these observations in relation to the clinical activity of SLE after sunlight exposure is discussed.

Autoimmune reaction in cryptorchidism?

The hypothesis that autoimmune reaction might be the cause of the degeneration of both testes in unilateral cryptorchidism was tested by examining testicular biopsies taken from cryptorchid patients during orchidopexy. The biopsies were studied by indirect and direct immunofluorescent methods, to detect possible circulating or tissue-fixed anti-testicular autoantibodies. Based on these studies the underlying cause of bilateral testicular degeneration in unilateral cryptorchidism seems not to be an autoimmune reaction.

Significance of antibodies to double-stranded DNA in 30 systemic lupus erythematosus patients.

Attention has been directed lately to antibodies reactive with double-stranded DNA (dsDNA) in systemic lupus erythematosus (SLE) patients, as these antibodies are of considerable diagnostic value and are thought to be involved in the pathogenesis of the disease. In the present study, the clinical and laboratory evaluations of 30 SLE patients in various stages of disease activity were correlated with the levels of anti-DNA antibodies, as detected by the methods of Farr and of Aarden et al. Sera of 65 patients in relapse or remission were examined with both techniques, and a discrepancy was found in only nine sera. In addition, in six patients, a differential analysis of the immunoglobulin classes of anti-dsDNA was performed according to the method of Aarden et al. The data obtained with this assay correlate well with SLE activity and thus may add an important step to the evaluation of SLE patients.

Carrier determined tolerance with various subclasses of murine myeloma IgG.

Groups of BALB/c mice were treated with various conjugates of 2,4 dinitrophenyl (DNP) and BALB/c myeloma proteins belonging to the four subclasses of IgG (IgG1, IgG2, IgG2b, IgG3). Immediately therafter, they were challenged with DNP-keyhole limpet hemocyanin in complete Freund's adjuvant and antibody to the hapten was measured by direct and indirect hemolytic plaque assay. The results show that all subclasses of IgG are effective as tolerance-inducing carriers. However, the ability of induce tolerance is dependent upon the concentration of hapten bound to each myeloma protein. Tolerogenic conjugates suppress both direct and indirect plaque-forming cells in all types of antibodies measured (IgG1, IgG2a, IgG2b, IgGa), whereas, non-tolerogenic conjugate failed to suppress them. The intact molecule of IgG but not its fragments (Fab, F(ab)2', Fc) appear necessary as tolerance-inducing carriers. It is suggested that the ability to induce tolerance is related to the capacity of the tolerogenic conjugates to cause receptor blockade.

Leukocyte inhibitory factor (LIF) in granuloma annulare: a comparative study between the generalized and the localized types.

Leukocyte inhibitory factor (LIF) was investigated in 9 patients with localized granuloma annulare and 8 patients with the generalized form of the disease. The control group consisted of 10 matched, apparently healthy subjects. LIF values were significantly higher in patients with granuloma annulare of both groups than in controls (p less than 0.05 and 0.01). However, no significant difference was revealed between the two groups of patients. Though the results seem to speak for a cell-mediated immune response in granuloma annulare, they do not add a further support to the previously demonstrated differences between the two forms of granuloma annulare.

Immunofluorescent antigluten antibody test. Titer and profile of gluten antibodies in celiac disease.

Circulating antibodies to gluten fractions have been detected in most patients with celiac disease during gluten ingestion. The various detection techniques, however, are rather complex and inadequate for routine clinical use. Recently, a new indirect immunofluorescent method, named the antigluten antibody (AGA) test, has been developed. To establish the reliability of the test we compared six groups of patients: (1) 15 patients with biopsy-proved celiac disease of whom 13 had positive test results (the other two had already been receiving a gluten-free diet for two to three weeks); (2) 13 malnourished patients without celiac disease who had damaged mucosa, of whom only two had positive test results; (3) 21 patients with celiac symptomatology but normal mucosa, of whom four had positive test results; (4) 42 patients with other intestinal tract diseases, of whom seven had positive test results; (5) 28 patients with extraintestinal diseases, of whom only two had positive test results; and (6) 26 patients with autoimmune diseases, of whom five had positive test results. All patients with celiac disease who had positive test results and who were receiving a gluten-containing diet had titers of 1:40 to 1:80 in the IgG class, while all other patients with positive AGA test results had a low titer of 1:10 to 1:40, in the IgM class mainly. We conclude that the AGA test is an effective screening tool for patients with celiac disease and may serve as a practical index of dietary gluten avoidance.