Leukocyte gene expression signatures in antineutrophil cytoplasmic autoantibody and lupus glomerulonephritis

Leukocytes play a major role in the development and progression of autoimmune diseases. We measured gene expression differences in leukocytes from patients that were antineutrophil cytoplasmic autoantibody (ANCA) positive, patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), and healthy donors to explore potential pathways for clinical intervention. Leukocyte gene expression profiles were determined on Affymetrix U133A/B chips in 88 autoimmune patients, 28 healthy donors, and healthy donor leukocyte cell subtypes that were activated . Comparison of gene expression in leukocytes identified differentially expressed signature genes that distinguish each donor source. The microarray expression levels for many signature genes correlated with the clinical activity of small vessel vasculitis in the ANCA patients; a result confirmed by quantitative real time-polymerase chain reaction for 16 relevant genes. Comparison with -activated leukocyte subtypes from healthy donors revealed that the ANCA signature genes were expressed by neutrophils while the SLE signature genes were expressed in activated monocytes and T cells. We have found that leukocyte gene expression data can differentiate patients with RA, SLE, and ANCA-related small vessel vasculitis. Monitoring changes in the expression of specific genes may be a tool to help quantify disease activity during treatment

Quasistatic delamination of sandwich-like Kirchhoff-Love plates

A quasistatic rate-independent adhesive delamination problem of laminated plates with a finite thickness is considered. By letting the thickness of the plates go to zero, a rate-independent delamination model for a laminated Kirchhoff-Love plate is obtained as limit of these quasistatic processes. The same dimension reduction procedure is eventually applied to processes which are sensitive to delamination modes, namely opening vs. shearing is distinguishe

The polarized image of a synchrotron-emitting ring of gas orbiting a black hole

High Energy Astrophysic

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials