Giant Cell Arteritis (GCA), Polymyalgia Rheumatica (PMR), ANCA Associated Vasculitis (AAV), Idiopathic Inflammatory Myopathies, IgG4-Related Diseases, Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), Connective Tissue Disease, Sarcoidosis, Interstitial Lung Disease Due to Systemic Disease (Disorder), Interstitial Lung Disease (ILD), Asthma Bronchiale, COPD
Conditions
Keywords
Autoimmune Diseases, Vasculitis, Large Vessel Vasculitis, Giant Cell Arteritis, Polymyalgia Rheumatica, ANCA Associated Vasculitis, Idiopathic Inflammatory Myopathies, IgG4-Related Diseases, Rheumatoid Arthritis, Psoriatic Arthritis, Connective Tissue Disease, Sarcoidosis, Interstitial Lung Disease
Brief summary
The AYLo study (AutoimmunitY and Loss of y - Investigating the Role of Hematopoietic Mutations and Mosaic Mutation in the Y Chromosome in Autoimmune Rheumatologic Diseases) aims to systematically investigate hematopoietic mutations, such as hematopoietic (mosaic) loss of the Y chromosome (mLOY), focusing on their underlying causes, pathophysiological significance, patterns of manifestation, and impact on disease progression in autoimmune, rheumatologic disorders. This research seeks to bridge existing knowledge gaps by exploring how such mutations influence immune homeostasis, cellular function, and susceptibility to inflammation-driven pathologies. Through the integration of advanced immunological profiling, the study aspires to uncover key mechanisms that drive the initiation, progression, and complications of autoimmune rheumatic diseases. These analyses will combine single nucleotide polymorphisms (SNP) arrays, multiplex assays, transcriptomics, and flow cytometry staining of peripheral blood mononuclear cells to delineate the interplay between hematopoietic mutations and immune dysregulation. A further objective is the development of a multimodal framework for disease-specific characterization, enabling precise mapping of mutation-driven phenotypes across diverse autoimmune conditions. This framework will incorporate clinical, molecular, and imaging data. Additionally, the AYLo study aims to explore the potential role of mLOY and other hematopoietic mutations as biomarkers for disease stratification, prognosis, and therapeutic response. The findings may open avenues for personalized treatment approaches, leveraging the molecular insights to inform targeted interventions and improve patient outcomes in autoimmune rheumatic disorders. By integrating translational and basic science approaches, this study has the potential to redefine current paradigms in autoimmune disease research and therapy.
Interventions
DIAGNOSTIC_TESTSingle nucleotide polymorphisms (SNP)
Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.
DIAGNOSTIC_TEST3'mRNA sequencing
3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.
DIAGNOSTIC_TESTEnzyme-linked immunosorbent assay (ELISA) and Legendplex Array
Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..
DIAGNOSTIC_TESTFlow Cytometry
Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.
DIAGNOSTIC_TESTLaboratory assessment
Serum Chemistry
DIAGNOSTIC_TESTAssessment of Pulmonary Involvement
Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.
Sponsors
University of Bonn
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male * \> 50 years * Diagnosis of arthritis (RA, PsA), collagen diseases (SLE, systemic sclerosis, Sjögren's syndrome, mixed connective tissue diseases), vasculitis (eGPA, GPA, MPA, IgG4-related disease, GCA, PMR), sarcoidosis, COPD, ILD or asthma bronchiale confirmed by the treating physician.
Exclusion criteria
* Female * \< 50 years Inclusion Criteria (Healthy controls): * Male * \> 50 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of the fraction of hematopoietic cells exhibiting mLOY. | Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis). | Detection and quantification of the fraction of hematopoietic cells exhibiting mLOY in peripheral blood using SNP. Unit of Measure: Percentage (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Immune Cell Phenotype | Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis | Identification and quantification of immune cell subtypes, using flow cytometry. Unit of Measure: Changes in levels (percentages). |
| Changes in Cytokine Profiles | Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis | Identification and quantification of cytokines using 3'-mRNA transcriptome analysis and ELISA/ Legendplex. Unit of Measure: Changes in levels (pg/mL) |
| Number of Participants with Detected Pulmonary Involvement | Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis | Detection of structural anomalies in the lung in clinical routine assessment using lung ultrasound, computed tomography, chest radiography and whole-body plethysmography. Unit of Measure: Number of participants. |
Countries
Germany
Contacts
Primary ContactSimon Michael Petzinna, MD
Backup ContactValentin Sebastian Schäfer, MD
Outcome results
None listed