Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Myeloidmutations commonly associated to neoplasia in patients who do not meet the diagnostic criteria for myelodysplastic syndrome are coined as clonal hematopoiesis of indeterminate potential (CHIP). CHIP-related mutations are somatic DNA mutations accumulating with aging, being found in approximately 10% of over 65. Chronic inflammation, mirrored by TNF-aexposure, has been reported to favor the expansion of CHIP-mutant clones, such as TET2- and JAK2-, but recent evidence suggests that CHIP-mutated clones contribute to chronic inflammation, as TET2-mutated myeloid clones manifest a hyper-inflammatory M1 status. We hypothesize that chronic inflammation concurs with age to CHIP-mutation appearance, i.e. they should be more precocious and frequent in rheumatic patients; moreover, CHIP-mutations are associated to more active rheumatic diseases.
Methods: We investigated the peripheral blood and synovial fluid myeloid cells from 4 rheumatoid arthritis (RA), 4 psoriatic arthritis (PsA), and 4 knee osteoarthritis (OA) patients (female 5, median age 73,5 years, range 53-91, median disease duration 10 years, range 7-20). To detect the presence of CHIP-mutations we used a high-throughput sequencing platform (Illumina NextSeq platform) for mutation screening of 78 genes known to be relevant in myelodysplastic diseases. We evaluated only variants known as pathogenic in COSMIC database, with a population frequency (MAF) < 0.1% described in dbSNP and in 1000 Genome Project.
Results: We found somatic mutations of JAK2, TP53, and TET2in 2/4 RA patients, GATA2-mutation in 1/4 PsA patients, and a small clone of SF3B1 in 1/4 OA cases. Mutated clones were found both in peripheral blood and synovial fluid of the patients. The patients with CHIP-mutations did not have a more active disease (DAS28-CRP 4.2±0.6 vs 5.1±1.2; p>0.05), but 1 RA patient with JAK2-mutation and 1 PsA patient had < 65years.
Conclusion: Our data suggests that CHIP-mutations are frequent in patients with chronic arthritis, also before 65 years. Understanding the mechanisms connecting somatic mutation-driven clonal hematopoiesis and chronic inflammation will be of great interest not only from a pathogenic point of view, but also in considering possible therapeutic options, such as JAK-inhibitors.
To cite this abstract in AMA style:De Santis M, Zampini M, Isailovic N, Generali E, Guidelli GM, Della Porta M, Selmi C. Mutations Associated with Clonal Hematopoiesis of Indeterminate Potential Are Found in Peripheral Blood and Synovial Fluid Macrophages from Patients with Rheumatoid and Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/mutations-associated-with-clonal-hematopoiesis-of-indeterminate-potential-are-found-in-peripheral-blood-and-synovial-fluid-macrophages-from-patients-with-rheumatoid-and-psoriatic-arthritis/. Accessed July 14, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mutations-associated-with-clonal-hematopoiesis-of-indeterminate-potential-are-found-in-peripheral-blood-and-synovial-fluid-macrophages-from-patients-with-rheumatoid-and-psoriatic-arthritis/