Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis.

Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying non-invasive, blood-based pathologic immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation in patients with LN and to identify correlates of renal parameters and treatment response.

An atlas of healthy and injured cell states and niches in the human kidney.

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations.

Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions.

Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells.

Plasma proteomics reveals tissue-specific cell death and mediators of cell-cell interactions in severe COVID-19 patients.

COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 COVID-19 patients and 78 symptomatic controls over serial timepoints using two complementary approaches, we uncover COVID-19 host immune and non-immune proteins not previously linked to this disease. Integration of plasma proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage, plasmablast, and T cell effector proteins.

Pulmonary Vascular and Right Ventricular Burden During Exercise in Interstitial Lung Disease.

Background: Pulmonary hypertension (PH) adversely affects patient's exercise capacity in interstitial lung disease (ILD). The impact of pulmonary vascular and right ventricular (RV) dysfunction, however, has traditionally been believed to be mild and clinically relevant principally in advanced lung disease states.

Research Question: The aim of this study was to evaluate the relative contributions of pulmonary mechanics, pulmonary vascular function, and RV function to the ILD exercise limit.

Publisher Correction: The immune cell landscape in kidneys of patients with lupus nephritis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical characteristics and renal prognosis associated with interstitial fibrosis and tubular atrophy (IFTA) and vascular injury in lupus nephritis biopsies.

Background: Interstitial fibrosis and tubular atrophy (IFTA) and vascular injury are frequent histologic features of lupus nephritis renal biopsies, but their clinical correlates and prognostic value are not well understood. This cohort study investigated demographic, clinical and laboratory characteristics, and outcomes, associated with IFTA and vascular injury in lupus nephritis.

Methods: Reports of all renal biopsies performed at an academic medical center (1990-2017) with WHO/ISN/RPS Class II-V lupus nephritis were reviewed.

Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma.

Treatment of cancer has been revolutionized by immune checkpoint blockade therapies. Despite the high rate of response in advanced melanoma, the majority of patients succumb to disease. To identify factors associated with success or failure of checkpoint therapy, we profiled transcriptomes of 16,291 individual immune cells from 48 tumor samples of melanoma patients treated with checkpoint inhibitors.

Insights into the epidemiology and management of lupus nephritis from the US rheumatologist's perspective.

Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus that disproportionately affects nonwhites and those in lower socioeconomic groups. This review discusses recent data on the incidence, prevalence, and outcomes of patients with lupus nephritis with a focus on low-income US Medicaid patients. We also review recent guidelines on diagnosis, treatment, and screening for new onset and relapses of lupus nephritis.

Stoichiometric requirements for trapping and gating of Ca2+ release-activated Ca2+ (CRAC) channels by stromal interaction molecule 1 (STIM1).

Store-operated Ca(2+) entry depends critically on physical interactions of the endoplasmic reticulum (ER) Ca(2+) sensor stromal interaction molecule 1 (STIM1) and the Ca(2+) release-activated Ca(2+) (CRAC) channel protein Orai1. Recent studies support a diffusion-trap mechanism in which ER Ca(2+) depletion causes STIM1 to accumulate at ER-plasma membrane (PM) junctions, where it binds to Orai1, trapping and activating mobile CRAC channels in the overlying PM. To determine the stoichiometric requirements for CRAC channel trapping and activation, we expressed mCherry-STIM1 and Orai1-GFP at varying ratios in HEK cells and quantified CRAC current (I(CRAC)) activation and the STIM1:Orai1 ratio at ER-PM junctions after store depletion.

STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1.

Store-operated Ca(2+) channels activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER) are a major Ca(2+) entry pathway in nonexcitable cells and are essential for T cell activation and adaptive immunity. After store depletion, the ER Ca(2+) sensor STIM1 and the CRAC channel protein Orai1 redistribute to ER-plasma membrane (PM) junctions, but the fundamental issue of how STIM1 activates the CRAC channel at these sites is unresolved. Here, we identify a minimal, highly conserved 107-aa CRAC activation domain (CAD) of STIM1 that binds directly to the N and C termini of Orai1 to open the CRAC channel.

Cryptosporidium parvum mixed genotypes detected by PCR-restriction fragment length polymorphism analysis.

Combinations of 10 Cryptosporidium parvum oocysts, with various ratios of genotype I to genotype II, were isolated and subjected to PCR-restriction fragment length polymorphism analysis. Amplification of both genotypes in these samples ranged from 31 to 74% and yielded no information about the genotype proportions. In addition, since both genotypes were not always detected, amplification of a single genotype is not conclusive evidence that the sample contains only a single genotype.