Clinical practice: Coeliac disease

Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100–200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. Conclusion: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted

Immunostimulatory capacity of dental casting alloys on endotoxin responsiveness

Statement of problem Oral metal exposure has been associated with systemic and local adverse reactions, probably due to elemental release from the alloys. Although supraphysiological concentrations of salts from dentally applied metals can activate innate cells through TLR4 (Ni, Co, Pd) and TLR3 (Au), whether direct exposure to solid alloys can also trigger innate immune reactivity is still unknown. Purpose The purpose of this in vitro study was to determine whether dental cast alloy specimens can activate innate cells and influence their responsiveness to bacterial endotoxin. Material and methods Human monocyte-derived dendritic cells (MoDC) and THP-1 cells were cultured on top of different alloy specimens (Ni-Cr, Co-Cr, Pd-Cu, Pd-Ag, Ti-6Al-4V, amalgam, gold, and stainless steel) or in alloy-exposed culture medium with or without endotoxin (lipopolysaccharide [LPS]; Escherichia coli 055:B5). Interleukin-8 (IL-8) production was used as the parameter for innate stimulation and evaluated by enzyme-linked immunosorbent assay after 24 hours of culture. The statistical significance of the effects of various casting alloys on the secretion of IL-8 was analyzed by using the nonparametric Wilcoxon rank sum test (α=.05). Results Dental cast alloys induced IL-8 production in MoDC and THP-1 cells, with Au and Pd-Cu providing the strongest stimulation. The alloy-exposed culture media tested contained sufficient stimulatory metal ions to induce detectable IL-8 production in THP-1 cells, except for the Ni-Cr and stainless steel exposed media. Au and Pd-Cu alloys were also most effective in potentiating LPS responsiveness as measured by IL-8 production. Conclusions Using an in vitro culture system to expose MoDC and THP-1 cells to different alloy specimens this study showed that contact with the solid alloys, in particular when they contain Pd or Au, can trigger innate immune responses and augment responsiveness to bacterial endotoxin

Persistent Immune Tolerance to Nickel and Chromium by Oral Administration Prior to Cutaneous Sensitization

Oral administration of allergens, foreign proteins, or cell- bound antigens may induce systemic suppression of subsequent humoral and cell-mediated immune responses (“oral tolerance”) The induction of specific immune tolerance provides a potential strategy for treatment of T-cell dependent immune diseases. Therefore, in depth studies into reconditions for optimal and persistent tolerance induction are mandatory. Here we report on such studies in a guinea pig model using the non-cross-reactive contact allergens nickel and chromium. Feeding per os of nickel sulfate or potassium. dichromate did not trigger systemic TDTH-effector functions. Instead, short feeding periods led to a close-dependent, and metal-specific, suppression of subsequently induced allergic contact hypersensitivity. Administration of the allergens onto the oral mucosa was most effective in the induction of immune tolerance. When first sensitizing attempts were delayed until 1 year after feeding, the degree of unresponsiveness was reduced. In contrast, with cutaneous contacts starting Shortly after the feeding period, tolerance was fully stable and undiminished for at least 2 years. Thus, in orally treated guinea pigs cutaneous contacts provide boosting tolerogenic signals, supporting the view that oral tolerance does not result from clonal deletion but from active antigen-specific immunosuppression. Indeed, unresponsiveness to cutaneous immunization could be transferred by lymphoid cells from fed guinea pigs in a metal-specific way

Increased production of tumor necrosis factor α, and not of interferon γ, preceding disease activity in patients with multiple sclerosis

Objective: To study whether tumor necrosis factor (TNF) α or interferon (IFN) γ production by stimulated white blood cells precedes or accompanies clinical and magnetic resonance imaging signs of disease activity in patients with multiple sclerosis. Design: Prospective study with a follow-up of 9 months. Setting: Patients visiting an outpatient university clinic. Patients: The 30 Amsterdam-based patients (28 completing all evaluations) participating in a multicenter, randomized, placebo-controlled, double-blind trial of a chimeric anti-CD4 antibody in the treatment of active relapsing-remitting and secondary progressive multiple sclerosis. Patients in both treatment arms were included, because for these patients anti-CD4 treatment in this study did not affect TNF-α and IFN-γ production and did not reduce signs of disease activity on magnetic resonance imaging. Main Outcome Measure: Distribution of classes of TNF-α and IFN-γ production (expressed as z scores) in patients with or without clinical or magnetic resonance imaging signs of disease activity. Results: One month preceding exacerbations of multiple sclerosis, there was a shift toward higher z scores of TNF-α production (P<05), but not of IFN-γ production. There was no statistically significant relationship between IFN-γ and TNF-α production and magnetic resonance imaging markers of multiple sclerosis activity. Conclusion: The production of TNF-α, and not of IFN-γ, is significantly higher in patients with multiple sclerosis before exacerbations than in patients with stable disease. Although present, this relationship is too weak to use TNF-cα production as a surrogate marker of disease activity in multiple sclerosis

The prevalence of hypothyroidism after treatment for laryngeal and hypopharyngeal carcinomas: Are autoantibodies of influence?

Conclusions. The incidence rate of hypothyroidism after treatment for laryngeal and hypopharyngeal cancer is high, especially after combination treatment. An association between hypothyroidism and autoantibodies was found. Objectives. The incidences of hypothyroidism and autoantibodies were assessed retrospectively in 156 patients with laryngeal and hypopharyngeal carcinoma who were treated with surgery and/or radiotherapy between 1977 and 2002. Patients and methods. Patients treated for T2-T4 carcinoma or a recurrence after T1 who visited the outpatient clinic for their regular follow-up visit were included. All patients were evaluated for the development of hypothyroidism, defined as increased thyroid-stimulating hormone level (>4.5 mU/L) and the presence of autoantibodies. A questionnaire regarding symptoms was administered. Results. The prevalence of undiagnosed hypothyroidism following treatment of laryngeal carcinoma was 28.2%: 18.6% subclinical hypothyroidism and 9.6% clinical hypothyroidism. The prevalence of circulating antithyroid antibodies (anti-thyreoperoxidase and/or anti-thyreoglobulin) was 10.5%. Univariate analysis showed that patients with laryngectomy, hemithyroidectomy, ipsilateral neck dissection and autoantibodies had a higher risk of hypothyroidism. The combination of surgery and radiotherapy increased the risk. Symptoms such as weight gain and cold intolerance were significantly associated with hypothyroidism. Multivariate analysis showed hemithyroidectomy, autoantibodies, weight gain and cold intolerance to be prognostic factors for the development of hypothyroidism