Sjogren's syndrome (SS) is thought to be uncommon in children. An epidemiological study to describe the clinical features distinguishing SS in Japanese children was performed by sending questionnaires t o hospitals. A total of 61 cases of SS were reported from 1290 hospitals. The diagnosis of SS was based on histopathological changes and/or sialographic changes in the salivary glands. Forty-two cases had primary SS and 19 were secondary SS with other autoimmune disorders. Fourteen cases (65%) of secondary S S were associated with systemic lupus erythematosus. In primary SS, the initial symptoms were systemic manifestations (fever, exanthema, arthralgia, etc) except for sicca symptoms. In laboratory studies, antinuclear antibodies, elevated serum IgG, rheumatoid factor. anti-Ro/SS-A antibodies and anti-LdSS-B antibodies were frequently observed.
SUMMARYWe studied allergenic determinants that induce hypersensitivity to OVA, the major allergen in egg allergy, using immunoblot and histamine release assays. Immunoblot analysis demonstrated a part of the OVA epitope was in the C-terminal region comprising residues 347-385 (OVA347-385). Histamine was released from basophils of a patient with egg allergy upon stimulation with the OVA fragment corresponding to OVA347-385. Furthermore, detailed epitope mapping using overlapping peptides (residues 347-366, OVA-A; residues 357-376, OVA-B; and residues 367-385, OVA-C) in the OVA 347-385 region was carried out using the histamine release assay. In order for histamine release from basophils to occur, the allergen must possess two or more allergenic determinants located on the protein molecule at distances that would be equivalent to the distances between IgE molecules on the membrane surface. These results suggest that there are at least two epitopes that bind IgE antibodies on each OVA peptide. In addition, one epitope that binds IgE antibodies in two patients appears to reside in the haptenic peptide OVA357-366 (OVABl). The histamine release from basophils stimulated by OVA-B was completely inhibited by OVA-B1 in one of these patients. Similarly, OVA-B1 inhibited the histamine release produced by OVA-A in the other by more than 40%. These results suggest that haptenic synthetic peptides could regulate the allergic reaction in the effector phase if common epitope(s) recognized by IgE antibodies in the patients with egg allergy can be found. These are the first studies that provide an antigen-specific approach to inhibiting histamine release from basophils by a haptenic peptide recognized by IgE antibodies in an allergic disorder.
Keywords auloanlibody thyroid peroxidase epitope autoimmunity chronic thyroiditis SUMMARY A significant percentage (64%) of healthy subjects was found to contain anti-thyroid peroxidase (TPO) antibodies in their sera. However, in contrast with IgG from sera of patients with chronic thyroiditis, IgG from sera of healthy subjects did not inhibit TPO activities both in guaiacol and iodide assays. In addition, anti-TPO antibodies from healthy subjects did not block the inhibition of enzyme activities by anti-TPO antibodies from patients. These findings suggest that anti-TPO antibodies from healthy subjects do not bind to the epitopes relating to substrate-combining sites of TPO. Thus, the specificities of anti-TPO antibodies in healthy subjects may differ from those in eases of chronic thyroiditis.
To delineate the antigenic determinants on thyroglobulin (Tg) recognized by serum autoantibodies and peripheral blood T cells from patients with chronic thyroiditis, we studied the reactivities of three different Tg preparations, i.e. enzyme-digested Tg fragments, physically or chemically denatured Tg, or Tg with differing iodine contents. Human Tg was digested with staphylococcal V8 protease, and the fragments were separated by high performance liquid chromatography. The autoantibodies reacted with the larger fragments, but their ability to bind to small fragments was limited. On the other hand, T cells reacted similarly with all fragments, regardless of mol wt. The autoantibodies bound little to denatured Tg after its disulfide bonds were destroyed with dithiothreitol or 2-mercaptoethanol, while the reactivity of heat-denatured Tg was partially decreased, and that of Tg denatured with sodium dodecyl sulfate was conserved. Conversely, T cells reacted with Tg denatured by heating or dithiothreitol treatment. These results indicate that autoantibodies recognize mainly a conformational structure of Tg, presumably containing disulfide bonds, whereas T cells recognize the primary structure of Tg. Variations in the iodine content of Tg were not associated with altered reactivity with autoantibodies or T cells. We propose that variations in Tg conformation related to iodination of the molecule do not contribute significantly to its reactivity with autoantibodies and T cells. In addition, T cells reacted with the smaller Tg fragments containing few T3 or T4 residues to a greater extent than they did with larger Tg fragments with the same amount of T3 or T4 as native Tg. Therefore, it appears that the Tg-reactive T cells predominantly recognize determinants on the Tg molecule that are unrelated to hormone-containing sites.
The number of patients with juvenile-onset Sjögren's syndrome (SS) has recently increased. However, there is no drug that is safe and effective for the xerostomia that occurs in patients of this age group. We evaluated the efficacy and safety of orally administered pilocarpine hydrochloride for juvenile-onset SS patients. Five female patients, aged from 9 to 16 years, received 5-10 mg/day for 4 weeks. On days 1 and 28, salivary production was measured by the Saxon test, and patients completed subjective self-evaluations of xerostomia symptoms and were asked about changes in water intake and overall improvement of dry mouth on day 28. After 4 weeks of pilocarpine administration, salivary production increased significantly in all patients, and overall status was assessed as "improved" in all patients. One patient had excessive sweating. No serious adverse events or laboratory examination abnormalities correlated with pilocarpine administration were found. In conclusion, the results of this study suggest that orally administered pilocarpine is safe and effective for treating xerostomia in juvenile-onset SS patients. This is the first report of the efficacy of pilocarpine for juvenile SS patients; further evaluations are needed to confirm our result.
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