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Recruiting NCT06696027

AYLo - AutoimmunitY and Loss of y

Observational Giant Cell Arteritis (GCA) Polymyalgia Rheumatica (PMR) ANCA Associated Vasculitis (AAV) Idiopathic Inflammatory Myopathies

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Single nucleotide polymorphisms (SNP), 3'mRNA sequencing, Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array, Flow Cytometry.
Who it may be relevant to
Registry conditions: Giant Cell Arteritis (GCA), Polymyalgia Rheumatica (PMR), ANCA Associated Vasculitis (AAV), Idiopathic Inflammatory Myopathies. Basic parameters: from 50 years · Male.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Germany
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Investigating the Role of Hematopoietic Mutations and Mosaic Mutation in the Y Chromosome in Autoimmune Rheumatologic Diseases

Overview

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 test Single nucleotide polymorphisms (SNP)
    Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.
  • Diagnostic test 3'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 test Enzyme-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 test Flow 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 test Laboratory assessment
    Serum Chemistry
  • Diagnostic test Assessment 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.

Primary outcome measures

  • Quantification of the fraction of hematopoietic cells exhibiting mLOY. [Time frame: Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis).]
Secondary outcome measures (3)
  • Changes in Immune Cell Phenotype [Time frame: Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis]
  • Changes in Cytokine Profiles [Time frame: Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis]
  • Number of Participants with Detected Pulmonary Involvement [Time frame: Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model
Case-control

Study locations

Germany · 1 center
  • Department of Rheumatology — Bonn

Identifiers

NCT: NCT06696027 · 2024-471-BO

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗