gms | German Medical Science

Deutscher Rheumatologiekongress 2024

52. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh)
34. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)
38. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

18.09. - 21.09.2024, Düsseldorf

Artikel

Artikel empfehlen

Development and performance of a DNA methylation based diagnostic precision biomarker for rheumatoid arthritis

Meeting Abstract

Suche in Medline nach

  • Karl Trygve Kalleberg - Age Labs AS, Oslo
  • Espen Riskedal - Age Labs AS, Oslo
  • Arne Søraas - Age Labs AS, Oslo
  • Maria Dahl Mjaavaten - Diakonhjemmet Hospital, Rheumatology, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Oslo
  • Grethe-Elisabeth Stenvik - Diakonhjemmet Hospital, Rheumatology, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Oslo
  • Joseph Sexton - Diakonhjemmet Hospital, Rheumatology, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Oslo
  • Guro Løvik Goll - Diakonhjemmet Hospital, Rheumatology, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Oslo
  • Silje Watterdal Syversen - Diakonhjemmet Hospital, Rheumatology, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Oslo
  • Per Hoffmann - Life & Brain GmbH, Bonn
  • Sanjanaa Nagarajan - Evonik (SEA) Pte Ltd., Asia Research Hub, Singapore
  • Kit Yeng Wong - Evonik (SEA) Pte Ltd., Asia Research Hub, Singapore
  • Florian Boehl - Evonik Operations GmbH, Research, Development & Innovation, Hanau-Wolfgang
  • Siri Lillegraven - Diakonhjemmet Hospital, Rheumatology, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Oslo
  • Espen Haavardsholm - Diakonhjemmet Hospital, Rheumatology, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Oslo

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. Deutscher Rheumatologiekongress 2024, 52. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immmunologie (DGRh), 34. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 38. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh). Düsseldorf, 18.-21.09.2024. Düsseldorf: German Medical Science GMS Publishing House; 2024. DocRA.07

doi: 10.3205/24dgrh158, urn:nbn:de:0183-24dgrh1582

Veröffentlicht: 18. September 2024

© 2024 Kalleberg et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Introduction: Diagnostic delay for seronegative rheumatoid arthritis (RA) is a major clinical problem. To this end, a software algorithm (“EarlyRA”) that utilises epigenetic patterns in patients’ blood for early detection of both seropositive and seronegative RA has been developed. The first version of “EarlyRA” was developed using whole-blood DNA-methylation (DNAm) profiles from 1,362 treatment-naïve RA patients, healthy controls, and controls with relevant diseases including unspecified arthritis. It demonstrated a sensitivity of 0.90 and specificity of 0.88 for RA [1]. Importantly the sensitivity and specificity were similar in both seronegative and seropositive RA.

The objective of the present study was to develop a custom DNAm array to improve cost-efficiency and turn-around time and to validate the array against the original EarlyRA algorithm [1].

Methods: A custom DNAm array was designed (Evonik Operations GmbH) and produced (Illumina Inc). DNAm (beta) values from 0 to 1, reflecting the methylation percentage, were measured from the same human whole blood sample standard on the custom array and compared between two independent laboratories; one in Singapore (Evonik SEA Pte Ltd) and one in Germany (Life & Brain GmbH). The EarlyRA algorithm was then adapted to the new array and verified using 24 previously analysed samples from the original EarlyRA validation (10 RA samples (anonymised), 4 non-RA samples (anonymised), 10 samples from healthy controls.

Results: The correlation of DNAm beta values from the custom array between the two laboratories was robust even for input DNA amounts as low as 250 ng (Table 1 [Tab. 1], Figure 1 [Fig. 1]). The EarlyRA algorithm also correctly classified 24 samples analysed with the custom microarray (Figure 2 [Fig. 2]).

Conclusion: We have previously reported that EarlyRA accurately discriminates between seronegative and seropositive RA from other arthritides and healthy controls. We now demonstrate that EarlyRA can reliably utilise data generated from a newly developed custom array, improving accessibility and reliability for adoption by clinical laboratories.

Disclosures: Karl Trygve Kalleberg, Espen Riskedal, and Arne Søraas are shareholders of Age Labs AS, the company developing the EarlyRA test.

Sanjanaa Nagarajan and Kit Yeng Wong are employees of Evonik (SEA) Pte Ltd. and Florian Boehl is an employee of Evonik Operations GmbH all of whom are designing and developing custom microarrays.

Per Hoffman is employee of Life & Brain GmbH a service provider processing the custom microarray.

Gliederung

References

1.
Riskedal E, et al. Development and Performance of a Diagnostic Precision Biomarker for Seronegative Rheumatoid Arthritis Based on DNA Methylation in Blood. In: ACR Convergence 2022; 2022 Nov 10-14; Philadelphia, PA. Abstract number: 0531. Available from: https://acrabstracts.org/abstract/development-and-performance-of-a-diagnostic-precision-biomarker-for-seronegative-rheumatoid-arthritis-based-on-dna-methylation-in-blood/ Externer Link