Related Experiment Video
Updated: Jun 2, 2026

Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
The interaction between HLA shared epitope alleles and smoking and its contribution to autoimmunity against several
Annemiek Willemze1, Diane van der Woude, Wendimagegn Ghidey
1Leiden University Medical Center, Leiden, The Netherlands. a.willemze@lumc.nl
Objective:
Recent data suggest that a gene-environment interaction between smoking and the HLA shared epitope alleles plays a role in shaping the autoimmune reaction to specific citrullinated antigens. This study was undertaken to determine the effects of HLA shared epitope alleles and tobacco exposure on the immune response against various citrullinated antigens. These associations were analyzed in the anti-citrullinated protein antibody (ACPA)-positive stratum to control for the possibility that the associations found are explained by the known interaction between HLA shared epitope alleles and tobacco exposure on ACPA status.
Methods:
In 661 patients with rheumatoid arthritis, reactivity against several citrullinated antigens from vimentin, fibrinogen, enolase, and myelin basic protein was determined by enzyme-linked immunosorbent assay. The effects of the HLA shared epitope alleles and tobacco exposure were assessed by logistic regression analysis. Biologic interaction was analyzed by investigating whether the effects of the risk factors combined exhibited departure from additivity.
Results:
A significant interaction between tobacco exposure and HLA shared epitope alleles was found for the presence of ACPA as reported previously. When these interaction effects were studied for several ACPA "fine specificities," significant interactions were noted for several citrullinated peptides. However, these interactions were not present after stratification for ACPA status, indicating that the interaction between tobacco exposure and HLA shared epitope alleles influences autoimmunity not to specific citrullinated antigens, but rather to ACPA development.
Conclusion:
Our data indicate that the gene-environment interaction between HLA shared epitope alleles and smoking does not appear to shape the reactivity of the ACPA response. These data suggest that smoking promotes nonspecific citrullination rather than citrullination of specific antigens.
More Related Videos
09:25Methods to Evaluate Cytotoxicity and Immunosuppression of Combustible Tobacco Product Preparations
Published on: January 10, 2015
10:21Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification
Published on: September 20, 2024
Related Concept Videos
Autoimmune Disorders
Concept and Mechanism of Autoimmune Diseases
The immune system...
Inflammatory Bowel Disease III: Crohn's Disease
Graves' Disease I: Introduction
Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Cross-reactivity
Asthma I: Introduction