Session Title: Rheumatoid Arthritis – Etiology and Pathogenesis Poster III
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: 1) To identify and characterize the alterations present in the splicing machinery in leukocyte subsets of Rheumatoid Arthritis (RA) patients, and 2) To evaluate their influence on the activity of the disease and its atherothrombotic profile.
Methods: The study was conducted in monocytes, neutrophils and lymphocytes purified from 74 RA patients and 29 healthy donors (HD). By using a microfluidic qPCR array, a set of 45 elements of the splicing machinery were evaluated, including the complete major and minor spliceosome components, and splicing factors with
Results: A global reduction of spliceosome components in the three leukocyte subsets from RA patients was observed, except for a key minor spliceosome component, RNU4ATAC, which was consistently over-expressed. The levels of those altered components were associated
Interestingly, eight spliceosome components, including two small nuclear RNA (
Mechanistic in vitro studies demonstrated the involvement of several spliceosome components in the altered inflammatory profile of RA leukocytes. Likewise, splicing machinery was deregulated by
Conclusion: 1) We have identified specific alterations in the splicing machinery of leukocytes from RA patients, associated with the activity of the disease, as well as with its inflammatory and atherothrombotic profile. 2) Several signatures involving common altered components of the spliceosome in leukocytes subsets may be used as novel biomarkers for the typification of the disease, avoiding complementary ultrasound or radiological tests. 3) The altered expression of the splicing machinery in leukocytes of RA patients might derive from their autoimmune and
Funding: ISCIII (PI15/01333 and RIER RD16/0012/0015) co-funded with FEDER
To cite this abstract in AMA style:Perez-Sanchez C, Ibáñez-Costa A, Alors-Perez E, Pedraza-Arévalo S, Patiño-Trives AM, Luque Tevar M, Ruiz-Limon P, Barbarroja N, Jiménez-Gómez Y, Abalos-Aguilera MC, Segui P, Ortega-Castro R, Calvo-Gutierrez J, Escudero-Contreras A, Collantes Estevez E, Castaño JP, Luque RM, Lopez-Pedrera C. Alterations of the Splicing Machinery in Leukocyte Subsets of Rheumatoid Arthritis Patients Modulate Their Inflammatory, Autoimmune and Atherothrombotic Profiles [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/alterations-of-the-splicing-machinery-in-leukocyte-subsets-of-rheumatoid-arthritis-patients-modulate-their-inflammatory-autoimmune-and-atherothrombotic-profiles/. Accessed July 11, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/alterations-of-the-splicing-machinery-in-leukocyte-subsets-of-rheumatoid-arthritis-patients-modulate-their-inflammatory-autoimmune-and-atherothrombotic-profiles/