AYLo - AutoimmunitY and Loss of y

Conditions studied

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

About this study

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 outcomes

• Quantification of the fraction of hematopoietic cells exhibiting mLOY. (Cross sectional. Newly diagnosed patients: At baseline and 12 months after diagnosis).)

Eligibility information

Study locations

• Department of Rheumatology, Bonn, North Rhine-Westphalia 53127 Germany