Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma

Simple Summary Some autoimmune diseases have been linked to an increased risk of non-Hodgkin lymphoma (NHL), but the evidence varies across different subtypes of NHL, and few studies have examined whether autoimmunity is more generally associated with disease risk. Given the rise in autoimmunity, as measured by antinuclear antibodies (ANA) over time in the U.S., it is important to evaluate its potential association with NHL risk. In this nested case-control study, we measured ANA and other autoimmune biomarkers in serum collected years prior to diagnosis for cases and controls. We demonstrate that the presence of ANA is associated with an increased risk of diffuse large B-cell lymphoma, a common subtype of non-Hodgkin lymphoma. We further show that specific autoimmune biomarkers are associated with an increased risk of NHL, especially diffuse large B-cell and marginal zone lymphoma. Our study establishes autoimmunity as a risk factor for diffuse large B-cell lymphoma.Abstract Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88-1.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15-2.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18-7.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02-12.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26-62.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor.