AYLo - AutoimmunitY and Loss of y

Recruiting

• Conditions: Connective Tissue Disease; Sarcoidosis; Interstitial Lung Disease Due to Systemic Disease (Disorder); Interstitial Lung Disease (ILD); Asthma Bronchiale; COPD; Giant Cell Arteritis (GCA); Polymyalgia Rheumatica (PMR); ANCA Associated Vasculitis (AAV); Idiopathic Inflammatory Myopathies

• Registration Number: NCT06696027
• Lead Sponsor: University of Bonn

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-11-15
• Study First Submitted: 2024-11-15
• Study First Submitted QC: 2024-11-15
• Study First Posted: 2024-11-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-10
• Primary Completion: 2025-12
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 500

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

Exclusion Criteria (Healthy controls):

• Female
• < 50 years
• autoimmune, rheumatological diease
• pulmonary precondition

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Department of Rheumatology; 🇩🇪 Bonn, NRW, Germany