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Abstract Number: 0037

Clonal Haematopoiesis of Indeterminate Potential (CHIP) Is Associated with Disease Activity in Rheumatoid Arthritis

Athena Chin1, Sue Branford2, Annabelle Small3, katie Lowe3, malcolm Smith4, Monika Kutyna5, Robert King2, Susanna Proudman6, Devendra Hiwase7 and Mihir Wechalekar8, 1Royal Adelaide Hospital, Tranmere, South Australia, Australia, 2SA Pathology, Adelaide, Australia, 3Flinders University, Adelaide, Australia, 4Flinders Medical Centre, Adelaide, Australia, 5South Australian Health and Medical Research Institute, Adelaide, Australia, 6Royal Adelaide Hospital and University of Adelaide, Medindie, South Australia, Australia, 7Royal Adelaide Hospital, Adelaide, Australia, 8Flinders Medical Centre, Bedford Park, Australia

Meeting: ACR Convergence 2024

Keywords: prognostic factors, rheumatoid arthritis

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Session Information

Date: Saturday, November 16, 2024

Title: RA – Etiology & Pathogenesis Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Clonal haematopoiesis (CH) of indeterminate potential (CHIP) is defined as the detection of recurrent somatic mutations in genes that are known to drive haematological malignancies (such as DNMT3A, TET2, ASXL1), at a variant allele frequency (VAF) of >2%, in individuals without haematological abnormalities. CHIP is associated with increased risk of haematological malignancy and cardiovascular morbidity. Notably, CH can provide selective fitness advantage to haematopoietic stem cells under the stress of chronic inflammation. We hypothesised that the chronic inflammatory microenvironment in rheumatoid arthritis (RA) provides selective advantage to haematopoietic stem cells, engendering CH. We therefore evaluated the prevalence and pattern of CHIP in RA and its relationship with disease activity (DA).

Methods: DNA was extracted from the peripheral blood of 50 patients presenting with recent onset RA (baseline) and was analysed with next generation sequencing, utilising a custom-designed myeloid gene panel for genes commonly associated with CH. Correlation between CH, patient demographics and disease parameters were then performed with Mann-Whitney U and chi-square tests.

Results: 20% (10/50) and 8% (4/50) RA patients harboured somatic mutations with VAF >0.5% and 2%, respectively. Patients >60yo were more likely to have CHIP (58.3% vs 18.4%; p=0.007) and VAF >2% (16.7% vs 5.3%; p=0.2). The prevalence in the >60yo group was significantly higher than the reported frequency of 5.6% in healthy controls. Furthermore, 10% (5/50) of RA patients had ≥1 variants.

The majority of 24 discrete pathogenic variants (VAF >0.5%) involved DNMT3A (45.8%), TET2 (20.8%) and ASXL1 (12.5%). Importantly, mutations associated with high risk of progression to myeloid malignancy (TP53, SRSF2 and JAK2) were detected. Baseline high DAS28 was associated with a higher frequency of CHIP mutations compared to low DAS28 (9.7% vs 5.3%; p=0.6). Those with high baseline DA and CHIP mutations were less likely to respond to therapy: 66.7% (2/3) of this group were classified as non-responders (DAS28 at 6months) vs. only 17.4% (4/23) without CHIP mutation VAF >2% (p=0.02).

Conclusion: Patients with RA have increased prevalence of CHIP, and are associated with high DA and poor response to therapy. Considering the potential risk of further clonal expansion in inflammatory states such as RA, our findings warrant prospective studies to further characterise CHIP in this subset of patients.

Supporting image 1

Prevalence of Clonal Haematopoiesis in our Rheumatoid Arthritis Cohort

Supporting image 2

Clonal Haematopoiesis variants within our Rheumatoid Arthritis Cohort

Supporting image 3

Patients with high disease activity at baseline and no response to treatment at 6months were more likely to have CHIP or have had any exposure to smoking.


Disclosures: A. Chin: None; S. Branford: None; A. Small: None; k. Lowe: None; m. Smith: None; M. Kutyna: None; R. King: None; S. Proudman: None; D. Hiwase: None; M. Wechalekar: None.

To cite this abstract in AMA style:

Chin A, Branford S, Small A, Lowe k, Smith m, Kutyna M, King R, Proudman S, Hiwase D, Wechalekar M. Clonal Haematopoiesis of Indeterminate Potential (CHIP) Is Associated with Disease Activity in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/clonal-haematopoiesis-of-indeterminate-potential-chip-is-associated-with-disease-activity-in-rheumatoid-arthritis/. Accessed .
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