Clinical trial NCT06696027: AYLo - AutoimmunitY and Loss of y
Official title: Investigating the Role of Hematopoietic Mutations and Mosaic Mutation in the Y Chromosome in Autoimmune Rheumatologic Diseases
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University of Bonn
Sponsor class: OTHER
First posted: 2024-11-19
Enrollment: 500
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Quantification of the fraction of hematopoietic cells exhibiting mLOY.
timeFrame: Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis).
Secondary outcomes:
measure: Changes in Immune Cell Phenotype
timeFrame: Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis
measure: Changes in Cytokine Profiles
timeFrame: Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis
measure: Number of Participants with Detected Pulmonary Involvement
timeFrame: Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Department of Rheumatology
state: NRW
Study officials:
References: