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1.
JCEM Case Rep ; 1(3): luad047, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37908567

RESUMEN

Maternally inherited diabetes and deafness (MIDD) syndrome refers to a rarely diagnosed disorder caused by pathogenic variants in mtDNA. It was first identified in 1992 and, to date, is considered underdiagnosed because of misclassification to type 1 or type 2 diabetes mellitus. MIDD reflects a multisystem metabolic syndrome commonly resulting in insulin-requiring diabetes and sensorineural deafness but can also lead to a broad range of other manifestations. The spectrum of pathology differs among individuals, likely because of varied degrees of heteroplasmy associated with mtDNA. Heteroplasmy also creates diagnostic difficulties, with a high index of suspicion required to diagnose MIDD in some cases. Here, we review a patient with MIDD who presented with an atypical clinical diabetes picture, additionally documenting his pedigree. To our knowledge, this is the first Cypriot reported with MIDD.

2.
Diagnostics (Basel) ; 12(5)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35626377

RESUMEN

Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights.

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