Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study

BMC Nephrology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 18, 2024

MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). is expressed in kidney, nasal mucosa respiratory tract, while only kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1. To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey members ADTKD registry September 2021, after the initial, severe wave COVID-19. We linked results previously obtained genotype plasma CA15-3 (mucin-1) levels created longitudinal related deaths. Surveys were emailed 637 individuals, responses from 89 132 ADTKD-UMOD individuals. 19/83 (23%) respondents reported prior infection vs. 14/125 (11%) (odds ratio (OR) 2.35 (95%CI 1.60–3.11, P = 0.0260). Including additional familial cases respondents, 10/41 (24%) individuals died 1/30 (3%) ADTKD-UMOD, OR 9.21 1.22–69.32), 0.03. The mean level 14 infected 27 uninfected 7.06 ± 4.12 10.21 4.02 U/mL (P 0.035). Over three years duration, our identified 19 deaths 360 (5%) 3 478 (0.6%) 0.0007). Multivariate logistic regression revealed following odds ratios (95% confidence interval) for deaths: 8.4 (2.9–29.5), transplant 5.5 (1.6–9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). Individuals are at eight-fold risk mortality Haplo-insufficient may be responsible.

Language: Английский

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Mucins 3A and 3B Are Expressed in the Epithelium of Human Large Airway

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13546 - 13546

Published: Aug. 31, 2023

Aberrant mucus secretion is a hallmark of chronic obstructive pulmonary disease (COPD). Expression the membrane-tethered mucins 3A and 3B (MUC3A, MUC3B) in human lung largely unknown. In this observational cross-sectional study, we recruited subjects 45–65 years old from general population Stockholm, Sweden, during 2007–2011. Bronchial mucosal biopsies, bronchial brushings, bronchoalveolar lavage fluid (BALF) were retrieved COPD patients (n = 38), healthy never-smokers 40), smokers with normal function 40). Protein expression MUC3A MUC3B biopsies was assessed by immunohistochemical staining. subgroup 28), mRNAs quantified brushings using microarray. Non-parametric tests used to perform correlation group comparison analyses. A value p < 0.05 considered statistically significant. localized ciliated cells. also expressed basal equal all study groups but emphysema had higher expression, compared those without emphysema. Smokers mRNA levels than non-smokers. male correlated negatively expiratory air flows. positively total cell concentration macrophage percentage, CD4/CD8 T ratio BALF. We concluded that large airways may be marker or play role pathophysiology airway obstruction.

Language: Английский

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The Potential Role of Ocular and Otolaryngological Mucus Proteins in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 24, 2023

Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness associated with constellation of other symptoms. While the most common symptom unrelenting fatigue, many individuals also report suffering from rhinitis, dry eyes and sore throat. Mucin proteins are responsible for contributing to formation mucosal membranes throughout body. These pathways contribute body’s defense mechanisms involving pathogenic onset. When compromised by pathogens epithelium releases numerous cytokines enters prolonged state inflammation eradicate any particular infection. Based on genetic analysis, computational theory modeling we hypothesize that mucin protein dysfunction may ME/CFS symptoms due inability form adequate layers body, especially in ocular otolaryngological leading low grade chronic exacerbation

Language: Английский

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