AYLo - AutoimmunitY and Loss of y

NCT06696027 | Recruiting

• 1 other identifier: 2024-471-BO
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

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

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

Outcome Measures

Primary Outcomes (1)

• Quantification of the fraction of hematopoietic cells exhibiting mLOY.

  Detection and quantification of the fraction of hematopoietic cells exhibiting mLOY in peripheral blood using SNP. Unit of Measure: Percentage (%).

  Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis).

Secondary Outcomes (3)

• Changes in Immune Cell Phenotype

  Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis

• Changes in Cytokine Profiles

  Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis

• Number of Participants with Detected Pulmonary Involvement

  Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis

Study Arms (13)

Giant Cell Arteritis (GCA)

Patients with GCA (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment

Polymyalgia Rheumatica (PMR)

Patients with PMR (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment

ANCA Associated Vasculitis (AAV)

Patients with AAV (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

IgG4 Related Diseases

Patients with IgG4 Related Diseases (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment

Idiopathic Inflammatory Myopathies (IIM)

Patients with IIM (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Rheumatoid Arthritis (RA)

Patients with RA (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Psoriatic Arthritis (PsA)

Patients with PsA (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Connective Tissue Diseases (CTD)

Patients with CTD (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Sarcoidosis

Patients with sarcoidosis (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Interstitial Lung Diseases (ILD)

Patients with ILD (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Chronic Obstructive Pulmonary Disease (COPD)

Patients with COPD (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Asthma Bronchiale

Patients with asthma bronchiale (cross sectional, newly diagnosed with follow-up after twelve months).

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Healthy Control Group

Age-/ gender matched healthy controls

Diagnostic Test: Single nucleotide polymorphisms (SNP); Diagnostic Test: 3'mRNA sequencing; Diagnostic Test: Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array; Diagnostic Test: Flow Cytometry; Diagnostic Test: Laboratory assessment; Diagnostic Test: Assessment of Pulmonary Involvement

Interventions

Single nucleotide polymorphisms (SNP) DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

ANCA Associated Vasculitis (AAV); Asthma Bronchiale; Chronic Obstructive Pulmonary Disease (COPD); Connective Tissue Diseases (CTD); Giant Cell Arteritis (GCA); Healthy Control Group; Idiopathic Inflammatory Myopathies (IIM); IgG4 Related Diseases; Interstitial Lung Diseases (ILD); Polymyalgia Rheumatica (PMR); Psoriatic Arthritis (PsA); Rheumatoid Arthritis (RA); Sarcoidosis

3'mRNA sequencing DIAGNOSTIC_TEST

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.

ANCA Associated Vasculitis (AAV); Asthma Bronchiale; Chronic Obstructive Pulmonary Disease (COPD); Connective Tissue Diseases (CTD); Giant Cell Arteritis (GCA); Healthy Control Group; Idiopathic Inflammatory Myopathies (IIM); IgG4 Related Diseases; Interstitial Lung Diseases (ILD); Polymyalgia Rheumatica (PMR); Psoriatic Arthritis (PsA); Rheumatoid Arthritis (RA); Sarcoidosis

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array DIAGNOSTIC_TEST

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..

ANCA Associated Vasculitis (AAV); Asthma Bronchiale; Chronic Obstructive Pulmonary Disease (COPD); Connective Tissue Diseases (CTD); Giant Cell Arteritis (GCA); Healthy Control Group; Idiopathic Inflammatory Myopathies (IIM); IgG4 Related Diseases; Interstitial Lung Diseases (ILD); Polymyalgia Rheumatica (PMR); Psoriatic Arthritis (PsA); Rheumatoid Arthritis (RA); Sarcoidosis

Flow Cytometry DIAGNOSTIC_TEST

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.

ANCA Associated Vasculitis (AAV); Asthma Bronchiale; Chronic Obstructive Pulmonary Disease (COPD); Connective Tissue Diseases (CTD); Giant Cell Arteritis (GCA); Healthy Control Group; Idiopathic Inflammatory Myopathies (IIM); IgG4 Related Diseases; Interstitial Lung Diseases (ILD); Polymyalgia Rheumatica (PMR); Psoriatic Arthritis (PsA); Rheumatoid Arthritis (RA); Sarcoidosis

Laboratory assessment DIAGNOSTIC_TEST

Serum Chemistry

ANCA Associated Vasculitis (AAV); Asthma Bronchiale; Chronic Obstructive Pulmonary Disease (COPD); Connective Tissue Diseases (CTD); Giant Cell Arteritis (GCA); Healthy Control Group; Idiopathic Inflammatory Myopathies (IIM); IgG4 Related Diseases; Interstitial Lung Diseases (ILD); Polymyalgia Rheumatica (PMR); Psoriatic Arthritis (PsA); Rheumatoid Arthritis (RA); Sarcoidosis

Assessment of Pulmonary Involvement DIAGNOSTIC_TEST

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.

ANCA Associated Vasculitis (AAV); Asthma Bronchiale; Chronic Obstructive Pulmonary Disease (COPD); Connective Tissue Diseases (CTD); Healthy Control Group; Idiopathic Inflammatory Myopathies (IIM); Interstitial Lung Diseases (ILD); Psoriatic Arthritis (PsA); Rheumatoid Arthritis (RA); Sarcoidosis

Eligibility Criteria

• Age: 50 Years+
• Gender Eligibility Details: Patients with XY chromosomes.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes male participants aged 50 years or older, divided into two groups: individuals with specific medical conditions (cases) and healthy controls. 1. Participants must have a diagnosis confirmed by the treating physician of one or more of the following conditions: Arthritis (RA, PsA), CTD (e.g., systemic lupus erythematosus \[SLE\], systemic sclerosis, Sjögren's syndrome, mixed connective tissue diseases), vasculitis ( eosinophilic granulomatosis with polyangiitis \[eGPA\], granulomatosis with polyangiitis \[GPA\], microscopic polyangiitis \[MPA\], IgG4-related disease, GCA + PMR), sarcoidosis, COPD, ILD, asthma bronchial 2. Healthy Controls: Healthy male participants aged 50 years or older without any of the following conditions: Autoimmune or rheumatological diseases Pulmonary preconditions 3. Exclusion Criteria: For both groups, females and individuals younger than 50 years are excluded.

You may qualify if:

• 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.

You may not qualify if:

• Female
• \< 50 years
• Male
• \> 50 years
• Female
• \< 50 years
• autoimmune, rheumatological diease
• pulmonary precondition

Sponsors & Collaborators

• University of Bonn: lead

Study Sites (1)

Department of Rheumatology

Bonn, North Rhine-Westphalia, 53127, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood, Pax Tubes, Serum, PBMC

MeSH Terms

Conditions

Giant Cell Arteritis; Polymyalgia Rheumatica; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Myositis; Immunoglobulin G4-Related Disease; Arthritis, Rheumatoid; Arthritis, Psoriatic; Connective Tissue Diseases; Sarcoidosis; Lung Diseases, Interstitial; Pulmonary Disease, Chronic Obstructive; Autoimmune Diseases; Vasculitis

Interventions

Polymorphism, Single Nucleotide; Flow Cytometry

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Systemic Vasculitis; Neuromuscular Diseases; Arthritis; Joint Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polymorphism, Genetic; Genetic Variation; Genetic Phenomena; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Central Study Contacts

Simon Michael Petzinna, MD

CONTACT

0049 151 382 337 07; Simon_Michael.Petzinna@ukbonn.de

Valentin Sebastian Schäfer, MD

CONTACT

0049 228 287 17000; valentin.schaefer@ukbonn.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 15, 2024
• First Posted: November 19, 2024
• Study Start: November 15, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)