Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters allele expression commitment, in support of two proposed mechanisms5,6 for the regulation of aRMAE. We tested peripheral blood mononuclear cells from individuals with IEIs with shared genetic lesions but discordant clinical phenotypes for aRMAE. Among two relatives who were heterozygous for a mutation in PLCG2 (delEx19), an antibody deficiency phenotype corresponds to selective mutant allele expression in B cells. By contrast, among relatives who were heterozygous for a mutation in JAK1 (c.2099G>A; p.S700N), the unaffected carrier T cells predominantly expressed the wild-type JAK1 allele, whereas the affected carrier T cells exhibited biallelic expression. Allelic expression bias was also documented in phenotypically discordant family members with mutations in STAT1 and CARD11. This study highlights the importance of considering both the genotype and the ‘transcriptotype’ in analyses of the penetrance and expressivity of monogenic disorders.

ABSTRACT Collagen is a key protein in mammals that maintains structural integrity within tissues. A failure in fibrillar collagen reorganization can induce cancer or fibrosis formation, such as in spinal cord injury (SCI), where the healing process after the initial trauma leads to the formation of scar tissue, which includes fibrosis. As there is no current treatment targeting the fibrotic process directly, a better understanding of collagen properties can thus help to apprehend malignant states. Characterization of collagen fibers has been widely explored on second‐harmonic generation (SHG) images, due to the label‐free nature of the SHG imaging technique. It has been performed with various fibers extraction methods such as curvelet transform (CT) implemented in the open‐source software CurveAlign. However, when it comes to investigating undergrowth collagen fibers (collagen fibers that are still under reorganization) as observed in SCI, the CT method becomes complex to tune for nonadvanced users in order to properly segment the fibers. To improve collagen detection in the case of undergrowth fibers, we propose a methodology based on the fingerprint enhancement (FP‐E) algorithm that requires fewer user input parameters and is less time‐consuming. Our method was extensively tested on SHG data from injured spinal cord samples. We obtained metrics that depicted changes in collagen organization over time, particularly a significant increase in fiber density, demonstrating the FP‐E algorithm was properly adapted to address the evolution of collagen properties after SCI. Besides the simpler tuning of the method compared to commonly used software, the combination with further characterization of the extracted fibers could lead to consider fibrillar collagen as a biomarker in diseases where fibers are under development. The FP‐E algorithm is provided in the article.

In this work, the first hyperpolarizability of Au x @Ag 100-x core-shell nanoparticles with x the gold molar fraction in percent and the gold core of which is 12 nm in diameter, is determined and compared to that of their corresponding laser annealed nanoparticles using hyper Rayleigh scattering experiments. Laser annealing transforms the initially composite Au x @Ag 100-x core-shell nanoparticles into alloyed Au x Ag 100-x homogeneous nanoparticles, providing a reference for comparison. It is observed that the evolution with the relative molar ratio between gold and silver of the first hyperpolarizability magnitude of both the Au x @Ag 100-x core-shell and the alloyed Au x Ag 100-x nanoparticles is driven by the SPR resonance enhancement occurring at the harmonic wavelength due to red shifting of the SPR band away from the harmonic wavelength. Furthermore, the first hyperpolarizability magnitude of the Au x @Ag 100-x core-shell nanoparticles is found to be about three orders of magnitude larger than that of the annealed alloyed Au x Ag 100-x nanoparticles. This feature may be attributed to the existence of the two nonlinearities, namely the surface nonlinearity due to the surrounding mediumsilver layer interface and the silvergold metal -metal interface constructively contributing due to their close localization. The core-shell morphology is thus highly beneficial in view of applications as compared to the alloyed one.