The exposure of *0401 mice, as well as mice carrying the RA-resistant gene, DRB1*0402, to cigarette smoke generated a similar response to native and citrullinated self-peptides [50], even though *0402 mice did not develop arthritis, suggesting an interaction between the impact of HLA genes and environmental factors on RA onset [53]. This evidence concerns the gene HLA-DRB1 and arthritic joint disease.