RESUMO
Autoimmune diseases develop over years - starting from a subclinical phenotype to clinically manifest autoimmune disease. The factors that drive this transition are ill-defined. To predict the turning point towards clinical disease and to intervene in the progress of autoimmune-mediated dysfunction, the establishment of new biomarkers is needed. Especially CD4 T cells are crucially involved in autoimmunity: first, during the initiation phase, because they lose their tolerance towards self-peptides, and second, by the subsequent ongoing presentation of self-peptides during the active autoimmune disease. Accordingly, changes in the degree of diversity of T cell receptor (TCR) repertoires in autoimmunity have been reported. These findings led to the hypothesis that transition from pre-disease to autoimmune disease is associated with an increase of abnormally expanded T cell clones that occupy large portions of the TCR repertoire. In this pilot study, we asked whether the ratio and the diversity of the TCR repertoires of circulating memory (CD45RO) and naïve (CD45RA) CD4 T cells could serve as a predictive factor for the development of autoimmunity. To find out, we analyzed the TCRß repertoires of memory and naïve CD4 T cells in a small cohort of four gender- and age-matched elderly patients having the autoimmune blistering disease bullous pemphigoid or non-melanoma skin cancers. We found that the extent of clonal expansions in the TCRß repertoires from the circulating memory and naïve CD4 populations did not differ between the patient groups. This result shows that the diversity of TCR repertoires from peripheral CD4 T cells does not reflect the manifestation of the skin-associated autoimmune disease BP and does not qualify as a prognostic factor. We propose that longitudinal TCR repertoire analysis of younger patients might be more informative.
Assuntos
Doenças Autoimunes , Penfigoide Bolhoso , Humanos , Projetos Piloto , Linfócitos T CD4-Positivos , Antígenos Comuns de Leucócito , Receptores de Antígenos de Linfócitos TRESUMO
Background: Burn injury continues to be a significant cause of morbidity and death, with infectious complications being the primary cause of death. Patients are susceptible to overwhelming infection secondary to both the physical breakdown of the skin and mucosal barrier and the immune dysfunction that accompanies the inflammatory response to a major burn. With resistance to traditional antibiosis looming as a serious threat to patient outcome, advancement in the treatment of burn infections is imperative. Methods: Between February 15 and March 15, 2020, a search of Pubmed and clinicaltrials.gov was performed using search terms such as "burn immunotherapy," "therapeutic microorganisms in burn," "burn infection clinical trials," and applicable variations. Results: Topical antimicrobial drugs continue to be standard of care for burn wound injuries, but personalized and molecular treatments that rely on immune manipulation of the host show great promise. We discuss novel therapeutics for the treatment of burn infection: Probiotics and therapeutic microorganisms, immune modulators, tailored monoclonal antibodies, and extracellular vesicles and proteins. Conclusions: The treatment strategies discussed employ manipulation of structure and function in host immune cells and pathogen virulence for improved outcomes in burn infection.
Assuntos
Queimaduras , Doenças Transmissíveis , Infecção dos Ferimentos , Queimaduras/terapia , Humanos , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
Dermabacter hominis is a common colonizer of the healthy human skin and is rarely detected as an opportunistic human pathogen. The genome sequence of the multidrug-resistant D. hominis strain 1368, isolated from blood cultures of a pyelonephritis patient, provides insights into the repertoire of antibiotic resistance genes.
RESUMO
Corynebacterium falsenii is a member of the natural microflora of wild and domesticated birds and is rarely detected in human clinical specimens. The chromosomal sequence of the type strain C. falsenii DSM 44353 comprises 2,677,607 bp and provides detailed insights into the evolution of Corynebacterium species assigned to the highly diverse cluster 3.
RESUMO
Corynebacterium argentoratense is part of the human skin microbiota and is occasionally detected in the upper respiratory tract of patients suffering from tonsillitis. The complete DNA sequence of the type strain DSM 44202 comprises 2,031,902 bp, yielding the smallest genome sequenced thus far for a corynebacterium associated with humans.