Immunohistochemical Marker for Na+ CP Type Vα (C-20) and Heterozygous Nonsense SCN5A Mutation W822X in a Sudden Cardiac Death Induced by Mild Anaphylactic Reaction

Abstract

A sudden death likely due to mild anaphylactic reaction in a young man is described. Autoptic, histologic, immunohistochemical, and laboratory findings were strongly consistent with the diagnosis of a mild anaphylactic reaction. Genetic molecular analysis, performed on formalin-fixed, paraffin-embedded tissues, showed a mutation described as W822X in a family with electrocardiographic pattern typical of Brugada Syndrome. It results in a nonsense mutation generating a truncated form of the channel protein. The mutation is due to a point substitution of a guanine with an adenine residue (G2466A). Immunohistochemistry and laser scanning confocal microscopy on sections from heart formalin-fixed, paraffin-embedded tissues led us to confirm the cellular localization of the Na+ CP type Valpha (C-20) at the intercalated disks of ventricular myocytes and nearly 50% reduction in Na+ channels expression in ventricular myocytes when compared with control cases. We suggest that the anaphylactic reaction that occurred in the young man could serve as a trigger mechanism, responsible for his sudden death with a SCN5A mutation associated with the Brugada syndrome.

Isolation and Characterization of CD276+/HLA-E+ Human Subendocardial Mesenchymal Stem Cells from Chronic Heart Failure Patients: Analysis of Differentiative Potential and Immunomodulatory Markers Expression

“…Spontaneous Ca(2 + ) release through RYR-2, a huge tetrameric protein, during diastole leads to a decrease in the SR Ca(2 + ) content [97]. This molecule is of key importance also for the large class of diseases known as channellopaties [98,99]. Other strictly myocardial markers, such as MYL-2 (slow cardiac myosin regulatory light chain 2, ventricular/cardiac muscle isoform), MYBPC3, TNNI3 (cardiac), and TNNI3K, were similarly not expressed by undifferentiated HSE-MSCs.…”

Novel Immunomodulatory Markers Expressed by Human WJ-MSC: an Updated Review in Regenerative and Reparative Medicine

“…In addition, the expression of connexin 43 [16] suggested the possibility to differentiate WJ-MSC into cardiomyocytes or other cardiac resident cell types [31] or to be directly administered to correct conduction defects and other heart diseases [32][33][34].…”

Anaphylactic Death: A New Forensic Workflow for Diagnosis

“…Several epidemiologic and experimental studies [9,28,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] have underlined the importance of immunohistochemical analyses and the concentrations of serum tryptase; however, based on the literature, this article is the first study that combines the two parameters for a specific diagnosis of anaphylactic death.…”

“…According to Turillazzi et al [39], in all cases, the larynx and pharynx were opened with forceps following the posterior median line and the glottis was observed; the sides were stretched outward to study the mucosa. Then, following the Ghon technique, abdominal organs were removed using the bloc method, taking care to preserve the integrity of vascular structures.…”