Sulphasalazine inhibits human antigen-specific immune responses in vivo.

OBJECTIVE: To study the effects of the antirheumatic drug sulphasalazine (SASP) on the immune system by analysing systemic and gut-associated immune responses. METHODS: A total of 23 healthy volunteers were treated with either SASP or placebo for 5 weeks in a double-blind fashion and immunised 2 weeks after the initiation of treatment. Specific immune responses were triggered by subcutaneous immunisation with tetanus toxoid and by peroral immunisation with inactivated influenza vaccine. The effects of treatment on specific immunity to tetanus and influenza were evaluated by enzyme-linked immunospot assay quantifying the number of circulating specific and total antibody-producing cells (spot-forming cells (SFC)) at 6, 8 and 10 days after immunisation. RESULTS: An immunosuppressive effect of SASP on systemic immune response was observed with a decrease in the total number of IgG-SFC, IgG anti-tetanus SFC and IgG anti-tetanus antibody levels in serum. SASP also exerted an immunosuppressive effect on the mucosa-associated immune system as seen from its down-regulating effect on the total number of circulating IgA SFC. CONCLUSIONS: These data show firstly that SASP exerts an immunosuppressive effect on defined immune responses to immunisation in vivo, and secondly that both mucosa-associated and systemic immunity are affected by SASP treatment.

Antitissue transglutaminase and antithyroid autoantibodies in children with Down syndrome and celiac disease.

OBJECTIVES: We measured circulating autoantibodies and evaluated the potential of circulating antitissue transglutaminase (tTG) antibodies to determine the presence of celiac disease (CD) in children with Down syndrome. METHODS: An ELISA based on recombinant human tTG was used to measure the levels of immunoglobulin A and immunoglobulin G antibodies in serum samples from 72 children with Down syndrome, 52 children with biopsy-verified CD, 21 disease controls with a normal small intestinal mucosa and 23 healthy controls. Of the 72 Down syndrome children, 11 under-went a small intestinal biopsy. RESULTS: Four of 72 children with Down syndrome were diagnosed as having CD and three of them had serum levels of immunoglobulin A tTG antibodies greater than 6 U/mL (668, 147 and 7 U/mL). One Down syndrome child with biopsyproven CD had normal levels of immunoglobulin A tTG. Two Down syndrome children had increased levels of immunoglobulin A tTG (13 and 7 U/mL) but none of these children had an intestinal biopsy performed. Of the 52 CD subjects (median 664 U/mL) one was negative for immunoglobulin A tTG (5 U/mL) and all healthy controls (median 1.2 U/mL) and disease controls (median 0.9 U/mL) had immunoglobulin A tTG antibody levels less than 6 U/mL. Two of four Down syndrome children with CD and 36 of 52 celiac children had increased serum levels of immunoglobulin G tTG antibodies. There was no correlation between the serum levels of tTG and antithyroid autoantibodies. CONCLUSIONS: Although the diagnosis of CD depends on histologic evaluation of intestinal biopsies, detection of anti-tTG antibodies provides a useful complementary diagnostic method for CD in children with Down syndrome.

Evidence for immunostimulatory effects of intramuscular gold in patients with rheumatoid arthritis: correlation with skin reactions.

OBJECTIVE: Intramuscular gold is a well documented treatment in rheumatoid arthritis (RA), but its mechanism of action is still poorly understood. From an observation that gold sodium thiomalate (GSTM) induces monocyte-derived interleukin 6 (IL-6) and IL-10 production in vitro, a hypothesis has been proposed that gold exerts its action mainly as a selective immunostimulator rather than as a general immunosuppressant. In this prospective study we investigated cytokine production in peripheral blood from patients with RA during treatment with GSTM. METHODS: A total of 20 patients with RA were treated with GSTM for at least 3 months. Disease activity was recorded at baseline, 12, 20, and 28 weeks. The ELISPOT method was used to measure spontaneous production of IL-6, IL-10, and interferon-g (IFN-g) from peripheral blood mononuclear cells (PBMC) at baseline and 4 and 12 weeks and production after incubation with GSTM in vitro, at different concentrations (0, 3, 12.5, 40 micro g/ml) at baseline. IL-6 and IL-10 concentrations in serum were measured with ELISA. RESULTS: The numbers of IL-10-producing cells were increased after 4 weeks' treatment with GSTM (p < 0.01). The numbers of cells spontaneously producing IL-6 were increased after 4 weeks (p < 0.01) and 12 weeks (p < 0.01). The numbers of IFN-g-producing cells were increased after 4 weeks (p < 0.01). Serum concentrations of IL-10 were increased after 4 weeks (p < 0.01). Serum concentrations of IL-6 were not changed at any timepoint. The in vitro effect of GSTM on IL-10 production from PBMC at baseline predicted development of skin reactions during GSTM treatment, with lack of skin reactions being associated with high gold induced IL-10 production (p < 0.05). There was no correlation between clinical response and cytokine production. CONCLUSION: This study indicates an immunostimulatory effect of GSTM treatment in patients with RA. The increase in IL-10 production during GSTM treatment may contribute to the positive effects of gold in RA.

Recombinant human tissue transglutaminase for diagnosis and follow-up of childhood coeliac disease.

Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions and for rapid follow-up. The aim of this study was to evaluate the potential of circulating anti-tissue transglutaminase (tTG) IgA and IgG antibodies in the diagnosis and follow-up of childhood celiac disease. An ELISA using recombinant human tTG was used to measure the levels of IgA and IgG anti-tTG antibodies in 226 serum samples from 57 children with biopsy-verified celiac disease, 29 disease control subjects, and 24 healthy control subjects. All samples were also analyzed for anti-endomysium antibodies (EMA). The levels of IgA and IgG anti-tTG antibodies correlated with the condition of the small intestinal villous structure and the serum levels of IgA EMA. All of the 25 serum samples obtained from untreated patients contained IgA anti-tTG antibodies, and 24 of 25 also had IgA EMA. Of the serum samples from 53 control children, two had IgA anti-tTG antibodies and two had IgA EMA. Children younger than 5 y of age with untreated celiac disease had the highest serum levels of both IgA and IgG anti-tTG. There was already an increase in IgA anti-tTG antibodies after 2 wk of gluten challenge (p < 0.01). Although the criteria-based diagnosis of childhood celiac disease still depends on histologic evaluation of intestinal biopsies, detection of anti-tTG antibodies provides useful complementary diagnostic information. The human recombinant tTG-based ELISA can be used as a sensitive and specific test to support the diagnosis and may also be used in the follow-up of treatment in childhood celiac disease.