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

Abstract

ObjectiveTakotsubo 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, ResultsA 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).ConclusionOur 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.

Titanium and Other Metal Hypersensitivity Diagnosed by MELISA® Test: Follow-Up Study

“…Metal hypersensitivity has been also associated with development of diverse diseases, such as nonischemic dilated cardiomyopathy [83], Takotsubo syndrome [57], connective tissue disease [56], fibromyalgia [84], and autoimmune thyroiditis [85]. In patients with diagnosed metal hypersensitivity and with health problems associated with metal medical devices, their health problems disappeared after the metal materials were removed [30,65].…”

“…Memory lymphocyte immune-stimulation assay (MELISA®) is based on the evaluation of the proliferation of peripheral blood lymphocytes in vitro after incubation with metal ions. This test modification for assessment of hypersensitivity reactions to various metals or nonmetal materials is used in many laboratories [30,43,[53][54][55][56][57][58]. MELISA® test could help the surgeon in selecting the most appropriate and tolerated implant material for the patients and may benefit the performance of the implantation by decreasing postoperative complications or revision surgeries.…”

A Pilot Study: Metal-Induced Immunotoxicity and Deaths of the 100 Vaccinees in the Republic of Korea for 2 Months of 2020 Flu Vaccination

“…Heavy metals such as mercury, cadmium, and aluminum can have immunotoxic eff ects through T-cell mediated, cellular-type hypersensitivity (Type IV delayed-type hypersensitivity) [7]. Th is delayed-type hypersensitivity occurs 24 to 48 hours aft er exposure and can be diagnosed by patch test, Lymphocyte Transformation Test (LTT), identifi cation of sensitized T cells by MELISA (Memory Lymphocyte Immuno-Stimulation Assay) [21] or morphological confi rmation of the presence of activated lymphocytes (lymphoblasts) [7]. Th is delayed-type hypersensitivity to mercury occurred in 14.8% of healthy persons [21].…”

“…Th is delayed-type hypersensitivity occurs 24 to 48 hours aft er exposure and can be diagnosed by patch test, Lymphocyte Transformation Test (LTT), identifi cation of sensitized T cells by MELISA (Memory Lymphocyte Immuno-Stimulation Assay) [21] or morphological confi rmation of the presence of activated lymphocytes (lymphoblasts) [7]. Th is delayed-type hypersensitivity to mercury occurred in 14.8% of healthy persons [21]. As seen in fi gures 1 & 2 of the current study, this type of metal-induc ed "delayed" hypersensitivity or immunotoxicity makes alveolar hypoxia, an acute form of Diff use Alveolar Damage (DAD), and stimulates infl ammatory changes, cytokines productions, free radical productions, alveolar congestion, and pulmonary edema [14].…”

“…Cadmium by itself may not cause hypersensitivity and autoimmunity as mercury does, but it may work as a co-stimulation (signal 2) instead of antigen recognition (signal 1) in the two-signal model of lymphocyte activation [20]. It is a weak sensitizer of the immune system and it skews immune responses towards to IgG1 Antibody Secreting Cell (ASC) production, and a T lymphocyte helper type 2 (Th 2) isotype [21].…”