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Antinuclear Antibodies Are Associated with an Increased Risk of 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.

SUBMITTER: Frost E

PROVIDER: S-EPMC10647241 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Frost Eleanor E Hofmann Jonathan N JN Huang Wen-Yi WY Parks Christine G CG Frazer-Abel Ashley A AA Deane Kevin D KD Berndt Sonja I SI

Cancers 20231031 21

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, ...[more]

PMID: 37958403

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Project description:BackgroundThe molecular diversity exhibited by diffuse large B-cell lymphoma (DLBCL) is a significant obstacle facing current precision therapies. However, scoring using the International Prognostic Index (IPI) is inadequate when fully predicting the development of DLBCL. Reprogramming lipid metabolism is crucial for DLBCL carcinogenesis and expansion, while a predictive approach derived from lipid metabolism-associated genes (LMAGs) has not yet been recognized for DLBCL.MethodsGene expression profiles of DLBCL were generated using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The LASSO Cox regression was used to construct an effective predictive risk-scoring model for DLBCL patients. The Kaplan-Meier survival assessment was employed to compare a given risk score with the IPI score and its impact on the survival of DLBCL patients. Functional enrichment examination was performed utilizing the KEGG pathway. After identifying hub genes via single-sample GSEA (ssGSEA), immunohistochemical staining and immunofluorescence were performed on lymph node samples from control and DLBCL patients to confirm these identified genes.ResultsSixteen lipid metabolism- and survival-associated genes were identified to construct a prognostic risk-scoring approach. This model demonstrated robust performance over various datasets and emerged as an autonomous risk factor for predicting the development of DLBCL patients. The risk score could significantly distinguish the development of DLBCL patients from the low-risk and elevated-risk IPI classes. Results from the inhibitory immune-related pathways and lower immune scores suggested an immunosuppressive phenotype within the elevated-risk group. Three hub genes, MECR, ARSK, and RAN, were identified to be negatively correlated with activated CD8 T cells and natural killer T cells in the elevated-risk score class. Ultimately, it was determined that these three genes were expressed by lymphoma cells but not by T cells in clinical samples from DLBCL patients.ConclusionThe risk level model derived from 16 lipid metabolism-associated genes represents a prognostic biomarker for DLBCL that is novel, robust, and may have an immunosuppressive role. It can compensate for the limitations of the IPI score in predicting overall survival and has potential clinical application value.

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

Publications

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

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