Diffuse large B cell lymphoma in rheumatoid arthritis express polyreactive and autoreactive B-cell receptor (BCRs) binding protein modifications
Authors' conclusion
The data suggest a possible link between polyreactivity and anti-MDA/MAA autoreactivity in RA-DLBCL lymphomagenesis. We hypothesize that high inflammation burden could increase antigen load which may trigger polyreactive and modified-protein B cell responses and/or maintain lymphoma cell survival.
Study context
- Population
- Rheumatoid arthritis (RA) patients with concurrent diffuse large B-cell lymphoma (RA-DLBCL) from the Swedish AUTO-LYMPHOMA cohortRA-DLBCL patients included
- Participants
- 22 patients
- Outcome
- Complete VH/VL lymphoma tissue sequences generated
Methodological detailsSwedish AUTO-LYMPHOMA cohort, multiplex PCR and Illumina sequencing, recombinant monoclonal antibodies, ELISA and solid-phase microarray (> 400 antigens)
- Swedish AUTO-LYMPHOMA cohort
- Multiplex PCR and Illumina sequencing
- Recombinant monoclonal antibodies
- ELISA and solid-phase microarray (> 400 antigens)
Main finding
As reported in the abstract
- RA-DLBCL patients with complete VH/VL sequences
- nine
- Patients with dominant paired heavy and light chain BCR sequences obtained
- six
- Clonotype diversity within the tumour
- generally low
Observational data: associations, not effects.
Further findings
Intra-clonal evolution
- Patients with amino acid variations in the diffuse large B-cell lymphoma (DLBCL) clonotype indicating intra-clonal evolution
- three
VH and VL somatic hypermutations
- Patients with few mutations (≤ 5 mismatches), of six
- Two
- Patients with high mutations (> 15 VH or VL mismatches), of six
- three
- No bias in VH/VL usage
Autoantigen binding of recombinant lymphoma BCRs
- Lymphoma BCRs expressed (from five patients)
- Six
- Bound MDA/MAA-protein
- five
- Polyreactive binding by in-house assays, of those binding MDA/MAA-protein
- Three
- Broad polyreactivity on the antigen array, of the three polyreactive
- two
- All patient-derived lymphoma BCRs CCP2 negative
- One patient: lymphoma BCR with high specificity to MDA/MAA-protein; another: binding only to methylated protein
Original publication
Diffuse large B cell lymphoma in rheumatoid arthritis express polyreactive and autoreactive BCRs binding protein modifications. Arthritis Res Ther. Published 27 October 2026. doi:10.
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