Remnant Epitope Autoimmunity in Human Abdominal Aortic Aneurysm: A Pilot Study with Elastin Peptides

BACKGROUND: Abdominal aortic aneurysm (AAA) is a prevalent disease affecting around 5% of the population aged more than 65 years. The exact etiology and physiopathology of AAA still raises questions, and elective surgery is currently the only treatment option for this often progressive disease. In this study, we hypothesized and tested a pathophysiological model that depicts AAA as an inflammation-triggered autoimmune disease with remnant vessel wall peptide fragments as the antigen. METHODS: A pilot study with male AAA patients (n = 14) and male controls (n = 8) was conducted. In both study groups, peripheral blood monocytes and plasma were separated from whole blood by centrifugation. An ELISpot test was performed on cultured white blood cells for the presence of elastin-specific T-lymphocytes. An Enzyme-linked immuno sorbent assay (ELISA) was performed on plasma for the presence of elastin-specific IgG molecules. RESULTS: ELISpot interferon-gamma secretion in AAA (7.7 ± 9.5%) and control (4.6 ± 3.5%) and ELISA anti-elastin IgG titer in AAA (77.5 ± 17.8%) and control (78.2 ± 31.5%) were not significantly different (P = 0.94 and P = 0.55, respectively). Both results are expressed as a percentage relative to the respective positive and negative control. CONCLUSIONS: The results of our pilot study did not indicate a clear and invariable autoimmune process directed against remnant elastin peptide fragments. Further research into the model mechanics and a possible antigen is still necessary. In the mean time, the model as presented here already offers a pathophysiological framework to further research into the possible remnant epitope-driven AAA etiology.status: publishe

Angelman syndrome and isovaleric acidemia: What is the link?

We report a toddler affected with Angelman syndrome and isovaleric acidemia (IVA). Such association was due to paternal uniparental isodisomy (UPD) of chromosome 15 in which the proband inherited two paternal copies of an IVA gene point mutation. As both diseases may have severe impact on neurodevelopment, adequate treatment of IVA should be discussed. In our patient however, the variant identified likely causes asymptomatic organic aciduria. Such findings emphasize that paternal UPD 15 can rarely lead to co-occurrence of Angelman syndrome and potentially treatable inborn errors of metabolism

U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics

Background: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be provided. Objectives: We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. Methods: Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data. Results: Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels. Conclusion: Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways