Polysomnographic findings in the ultra-rare McLeod syndrome: further documentation of sleep apnea as a possible feature.

STUDY OBJECTIVES: McLeod syndrome is a very rare multisystemic neurodegenerative disease linked to mutations in the XK gene. It has cardiac, neurologic, and neuromuscular manifestations and shares similarities with Huntington's disease. The aim of this study was to evaluate sleep patterns of patients affected by McLeod syndrome. METHODS: This retrospective case series of four males who underwent diagnostic polysomnography (mean age 53.8 ± 2.5 years) includes self-reported and objective evaluation of sleep using the Epworth Sleepiness Scale, genetic tests, documentation of clinical course and features, and laboratory-based full-night attended video-polysomnography. RESULTS: In three out of four patients, an Epworth Sleepiness Scale score ≥ 7 was evident. The average apnea-hypopnea index was 45.0 ± 19.0, with predominantly obstructive phenotype in three patients and predominant central events (central sleep apnea syndrome) in one patient. A significantly increased periodic limb movement index during sleep was observed in all patients. All patients tolerated continuous positive airway pressure or pressure controlled therapy. CONCLUSIONS: Polysomnography of all patients confirmed sleep apnea syndrome as a feature of McLeod syndrome. Three patients were diagnosed with obstructive sleep apnea and one with central sleep apnea syndrome. In addition, periodic limb movement index was increased in all patients. CITATION: Dieter M, Kevin P, Tobias V, et al. Polysomnographic findings in the ultra-rare McLeod syndrome: further documentation of sleep apnea as a possible feature. J Clin Sleep Med. 2024;20(3):339-344.

Single-cell RNA sequencing reveals in vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'

The in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we used single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induced transcriptional shifts by antigenic stimulation in vitro and took advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for reverse phenotyping. This allowed identification of SARS-CoV-2-reactive TCRs and revealed phenotypic effects introduced by antigen-specific stimulation. We characterized transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and showed correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.