Clinical trial NCT07000903: Occupational and Environmental Causes of Autoimmune Diseases
Official title: Occupational and Environmental Causes of Autoimmune Diseases: Clarifying Epidemiology and Improving Detection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lupus Erythematosus, Systemic
Systemic Sclerosis
Rheumatoid Arthritis
Lead sponsor: Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2025-06-03
Enrollment: 247
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Verify the added value of environmental exposure and immunophenotyping to establish a possible etiology of AID: the exposure and immune profiles will be determined in HBM blood and urine samples collected prospectively during the first SOC visit.
Primary purpose: BASIC_SCIENCE

Brief summary: The investigators hypothesize that part of the systemic autoimmune diseases (AID) patients might prove to have an occupational or environmental disease which is potentially preventable. The recognition of the occupational or environmental etiology of autoimmune disorders has major implications for patients and society and will generate opportunity for prevention and meaningful clinical intervention. The investigators intend to use the urine/blood exposure measurements to demonstrate the etiological role of environment in patients developing AID patients.

The investigators are mounting an epidemiological study to elucidate the environmental etiology of AID and their effects on the immune profile and disease course. A population-based case-control study will be done with adult patients with newly diagnosed systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis (n=100 per disease).

Detailed description: Systemic autoimmune diseases (AID) regroup a broad range of related diseases characterized by self-damaging immune responses. They mainly comprise systemic lupus, systemic sclerosis and rheumatoid arthritis and remain a significant clinical challenge. Rheumatoid arthritis (RA) is a degenerative disease associated with chronic inflammation that ultimately leads to joint damage, deformation and destruction. Systemic lupus erythematosus (SLE) is characterized by tissue injury resulting from immune responses and serological changes. This multifaceted etiology AID is initiated by the loss of tolerance to self-antigens and the accumulation of autoreactive B and T cells that promote autoreactive antibody production, immune complex formation and activated mononuclear cell infiltration in affected tissues. Finally, small vessels-vasculopathology, internal tissue fibrogenesis and thickening skin characterize systematic sclerosis (SSc) patients. These lesions derive from dysregulated immune functions altering connective tissue integrity.

Several risk factors have been pinpointed to explain the triggering of these AID. Scientists have managed to identify the main genetic factors. Susceptibility to AID is strongly associated to MHC class II polymorphisms and adaptive immunity activation (particularly effector T lymphocytes).

Nevertheless, several studies have also emphasized the contribution of environmental factors, which may function as triggers of innate immunity and may contribute to the breakdown of self-tolerance by modifying protein antigens. Cigarette smoking has proven to be a strong risk factor for seropositive RA and SLE. Cigarette smoke leads to post-translational modifications of antigens by citrullination (citrullinated antigens) that induce the production of anticitrullinated protein antibodies (ACPA) and the onset of ACPA-positive RA. Occupational factors may also cause or trigger AID. In a retrospective study conjointly performed by the Cliniques Universitaires Saint-Luc (CUSL) and UZ Leuven, it was concluded that an estimated 50% of male patients suffering from SSc have occupational exposure to silica and solvents. These findings indicate that environmental factors can provide clinically useful information in the management of AID patients.

Eligibility criteria: Inclusion Criteria:

* Clinically active lupus; systemic sclerosis; rheumatoid arthritis
* At least 18 years old
* Without first line disease-modifying therapy
* Written informed consent must be obtained before any assessment is performed

Exclusion Criteria:

* Younger than 18
* Wearers of metal prostheses

Primary outcomes:
measure: Exposome: quantification of the exposure of patients to environmental agents
timeFrame: Through the entire study, approximately during 30 months
measure: Exposome: quantification of the exposure of patients to agents
timeFrame: Through the entire study, approximately during 30 months
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
Study officials:
affiliation: UCLouvain - IREC
name: François Huaux, Pr
role: STUDY_DIRECTOR
References: