# Autoimmune disease-associated lymphomas: research progress and review

## TL;DR

Autoimmune diseases significantly increase the risk of certain lymphomas, and this review explores their connections, mechanisms, and treatment strategies.

## Contribution

This paper provides a comprehensive review of the epidemiology, mechanisms, and therapeutic approaches for lymphomas associated with autoimmune diseases.

## Key findings

- Autoimmune diseases like Sjögren’s syndrome are strongly linked to lymphomas, with a high standardized incidence ratio.
- Chronic inflammation and immune dysfunction drive lymphoma development through mechanisms like Treg/Breg dysfunction and TLS formation.
- Targeted therapies such as rituximab and BTK inhibitors show promise but are limited by the patient's baseline immune status.

## Abstract

Autoimmune diseases (ADs) are strongly associated with a significantly increased risk of lymphoma, with the standardised incidence ratio (SIR) markedly elevated in certain conditions, most notably in Sjögren’s disease (SjD) where an SIR as high as 18.8 has been reported. The risk is particularly prominent for diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma. This review systematically elucidates the epidemiological features, pathological mechanisms, risk factors, and therapeutic strategies of ADs-associated lymphomas. Epidemiological studies have confirmed strong associations between ADs such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and SjD with specific lymphoma subtypes, and these associations appear to be bidirectional. Core pathogenic mechanisms involve malignant transformation driven by the immune–inflammatory continuum: chronic antigenic stimulation and the inflammatory microenvironment result in regulatory cell (Treg/Breg) dysfunction, tertiary lymphoid structure (TLS) formation, and clonal evolution. Specific autoantibodies directly contribute to oncogenesis by interfering with intracellular signalling pathways, mimicking antigenic stimulation, and forming immune complexes, while infectious agents such as Epstein–Barr virus synergistically promote malignant transformation within immunosuppressive microenvironments. Risk factors encompass intrinsic disease features, treatment-related risks and gene–environment interactions. Clinical management must balance the dual imperatives of “controlling inflammation” and “minimising treatment-related risks”. Targeted therapies, such as rituximab and BTK inhibitors, as well as haematopoietic stem cell transplantation (HSCT), have offered hope, but prognosis remains profoundly influenced by baseline immune status. Future research should focus on risk stratification guided by multi-omics, the application of novel immunotherapies in the autoimmune setting, and the optimisation of multidisciplinary care models.