Vera Stejskal

Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease

BACKGROUND Connective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CTD often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD. METHODS Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögrens syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA(®) (Memory Lymphocyte Immuno Stimulation Assay). RESULTS In all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (P<0.0001). The most frequent allergens were nickel, mercury, gold and palladium. CONCLUSIONS Patients with SLE, RA and SS have an increased frequency of metal DTH. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in CTDs, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies.

Metals and Parkinson's disease: mechanisms and biochemical processes

Genetic background accounts for only 5 to 10% of the reported cases of Parkinsons disease (PD), while the remaining cases are of unknown etiology. It is believed that environmental factors may be involved in the causality of a large proportion of PD cases. Several PD genes are activated by xenobiotic exposure, and a link between pesticide exposure and PD has been demonstrated. Many epidemiological studies have shown an association between PD and exposure to metals such as mercury, lead, manganese, copper, iron, aluminum, bismuth, thallium, and zinc. This review explores the biological effects, the pathogenetic processes, genetic susceptibilities to metals as well as examining future strategies for PD treatment, such as chelation therapy.

Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome - Is There a Clinical Relevance?

Objective Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®. Methodology, Results A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). Conclusion Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients.

Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices

Abstract Aims To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden. Methods and results The cohort consisted of 20 men and 4 women (mean age: 62.3 ± 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 ± 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008). Conclusion Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.

MECHANISMS OF TARGET CELL KILLING BY ACTIVATED LYMPHOCYTES IN VITRO

Publisher Summary This chapter explores the mechanisms of target-cell killing by activated lymphocytes in vitro. A study described in the chapter examined the nature of the killer cells and the mechanisms underlying their cytotoxic reaction using activated human lymphocytes and Chang cells. Purified T-cells prepared by passage of PHA- or PWM-activated human lymphocytes through Ig/anti-Ig columns were much less cytotoxic than lymphocytes passed through control columns. The cytotoxicity of MLC-induced effector lymphocytes, however, was not reduced by Ig/anti-Ig column passage, thus, indicating their T-cell origin. The results suggest that cytotoxicity of lymphocytes prestimulated with mitogens is dependent on the presence of Fc+ cells and of antibody. Possibly, mitogen stimulation induces the production of antibody with reactivity for allogeneic target cells. This antibody may serve as recognition factor for Fc-receptor-bearing effector cells in this cytotoxic system. The evidence for production of allo- and autoantibodies by LPS-stimulated mouse spleen cells has been shown. Removal of EA+ activated lymphocytes, however, never completely abolished the cytotoxicity. This may be because of heterogeneity of the cellular Fc-receptors as revealed by the different assay procedures and/or by the participation of non-Fc-receptor-bearing lymphocytes in this cytotoxic reaction.

Species-specific lymphocyte-target cell interaction in vitro

Publisher Summary Lymphocytes prestimulated in vitro with PPD, PHA, or PWM lyse target cells within their own species more effectively than cells from other species. This chapter discusses the possibility that the preferential killing of target cells is based on lymphocyte recognition of some common species-specific structure on the target cell surface. The cytotoxic activity of human lymphocytes towards 51Cr-labeled human Chang cells is reduced by prior incubation on primate monolayers as compared to incubation on mouse monolayers. The addition of increasing numbers of unlabeled human or monkey cells to a fixed number of stimulated lymphocytes and 51Cr-Chang cells gradually decreases chromium release. Under similar conditions, mouse L cells are not inhibitory. The inhibitory capacity of unlabeled Chang cells decreases parallely with the time of trypsin treatment. The cytotoxic activity of in vitro activated lymphocytes is selective and specific. The species-specific cytotoxic effect seems to be based on lymphocyte recognition of certain surface structures followed by binding between the receptors on the effector cell and surface determinants of the target.