HLA and environmental interactions in sarcoidosis

Area of Science:

• Immunology
• Environmental Health
• Genetics

Background:

• Sarcoidosis is a complex systemic inflammatory disease of unknown cause, despite over a century of research.
• While genetic predisposition and environmental exposures are implicated, their interactions in sarcoidosis etiology remain under-investigated.

Purpose of the Study:

• To systematically investigate gene-environmental interactions in newly diagnosed sarcoidosis.
• To identify specific human leukocyte antigen (HLA) class II alleles and environmental exposures associated with sarcoidosis risk and phenotype.

Main Methods:

• Utilized the ACCESS dataset comprising 476 sarcoidosis cases and 476 matched controls.
• Performed high-resolution HLA class II typing and detailed environmental exposure histories.
• Evaluated interactions for exposures and HLA alleles present in >5% of the population with an odds ratio >1.0.

Main Results:

• Significant interaction found between HLA DRB1*1101 and occupational insecticide exposure (p < 0.10).
• Suggestive interactions noted for HLA DRB1*1101 with mold/musty odor exposure and HLA DRB1*1501 with occupational insecticide exposure (P < 0.15).
• HLA DRB1*1101 and insecticide exposure linked to extrapulmonary sarcoidosis (cardiac) and hypercalcemia (p<0.05); HLA DRB1*1101 and mold exposure linked to pulmonary-only sarcoidosis (P < 0.05).

Conclusions:

• Findings suggest that sarcoidosis can result from gene-environment interactions.
• Specific HLA alleles and environmental exposures are associated with sarcoidosis risk and clinical presentation.
• Further research on defined sarcoidosis phenotypes is needed to clarify these associations.