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.

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

Patients with XY chromosomes.

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.

Data are available upon reasonable request from the corresponding author.