Sequencing of Circulating Microbial Cell-Free DNA Can Identify Pathogens in Periprosthetic Joint Infections.

Background: Over 1 million Americans undergo joint replacement each year, and approximately 1 in 75 will incur a periprosthetic joint infection. Effective treatment necessitates pathogen identification, yet standard-of-care cultures fail to detect organisms in 10% to 20% of cases and require invasive sampling. We hypothesized that cell-free DNA (cfDNA) fragments from microorganisms in a periprosthetic joint infection can be found in the bloodstream and utilized to accurately identify pathogens via next-generation sequencing.

IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 lungs and inflammatory diseases with tissue inflammation.

Background: Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies.

Methods: To identify cellular phenotypes that may be shared across tissues affected by disparate inflammatory diseases, we developed a meta-analysis and integration pipeline that models and removes the effects of technology, tissue of origin, and donor that confound cell-type identification.

IFN- and TNF- drive a + + macrophage phenotype expanded in severe COVID-19 and other diseases with tissue inflammation.

Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases including rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease.

Synovial Tissue: Cellular and Molecular Phenotyping.

Purpose Of Review: This review provides a summary of recent molecular findings that have refined our understanding of the cell types that constitute human synovial tissue, particularly in patients with rheumatoid arthritis (RA).

Recent Findings: Recent advances in high-dimensional and single-cell assays have elucidated upwards of 20 cell subsets in the RA synovium. This includes novel fibroblast populations and lymphocyte phenotypes, which in many cases exhibit features that have not been found in other tissues thus far.

HBEGF macrophages in rheumatoid arthritis induce fibroblast invasiveness.

Macrophages tailor their function according to the signals found in tissue microenvironments, assuming a wide spectrum of phenotypes. A detailed understanding of macrophage phenotypes in human tissues is limited. Using single-cell RNA sequencing, we defined distinct macrophage subsets in the joints of patients with the autoimmune disease rheumatoid arthritis (RA), which affects ~1% of the population.