Startseite Forschung AG Skriner

AG Skriner

TheRAdiagnostics

Einleitung
Mitarbeitende
Publikationen

The group TheRAdiagnostics was established at the DRFZ in March 2021. We develop routine ELISA tests to predict and monitor therapy outcomes of patients suffering from rheumatoid arthritis (RA) and juvenile RA. These tests are based on the detection of autoantibodies and metabolites in the serum and are developed with small and medium-sized enterprises (SMEs). Using RA human modified protein macroarrays, we aim at identifying RA native and modified autoantigens for tolerance induction.

Furthermore, we were able to isolate bacteria from RA patients that citrullinate major RA autoantigens. This provides evidence of an infection-induced-autoimmunity model. The specific peptidylarginine deiminase (PAD) enzymes mediating this citrullination will be analyzed.

Based on our patents, we are trying to advance a proof of concept study in celiac disease and RA to develop a new auto/antigen-specific immune B cell elimination therapy.

To be able to monitor the response to therapeutic interventions of RA and juvenile arthritis patients, we develop multiplex autoantigen immunoassays. These assays should become generally available to clinicians to help them evaluate applied RA therapy for the benefit of patients. Our group also has a strong background in the development of novel therapeutic antibodies which mimic e.g. Tregs, or facilitate the depletion of antigen-specific plasma cells. To cure RA and celiac disease, we are developing a new auto/antigen-specific immune B cell elimination therapy. Elimination of specific bacteria inducing autoimmunity via enzymatic mimicry should help to stop early RA onset and to induce therapy success in RA.

 

Weiter zu Mitarbeitende

Dr Karl Skriner

Dipl biol Madeleine Jenning

Weiter zu Publikationen

1: Bianka Marklein 1, Madeleine Jenning 1 2, Zoltán Konthur 3 4 5, Thomas Häupl 1, Franziska Welzel 3, Ute Nonhoff 3, Sylvia Krobitsch 3, Debbie M Mulder 6, Marije I Koenders 6, Vijay Joshua 7, Andrew P Cope 8, Mark J Shlomchik 9, Hans-Joachim Anders 10, Gerd R Burmester 1, Aase Hensvold 7 11, Anca I Catrina 7, Johan Rönnelid 12, Günter Steiner 13 14, Karl Skriner 12. The citrullinated/native index of autoantibodies against hnRNP-DL predicts an individual “window of treatment success” in RA patients. Arthritis Res Ther 23, 239 (2021). https://doi.org/10.1186/s13075-021-02603-x

2: Kreye J, Reincke SM, Kornau HC, Sanchez-Sendin E, Corman VM, Liu H, Yuan M, Wu NC, Zhu X, Lee CD, Trimpert J, Hoeltje M, Dietert K, Stoeffler L, von Wardenburg N, van Hoof S, Homeyer MA, Hoffmann J, Abdelgawad A, Gruber AD, Bertzbach LD, Vladimirova D, Li LY, Barthel PC, Skriner K, Hocke AC, Hippenstiel S, Witzenrath M, Suttorp N, Kurth F, Franke C, Endres M, Schmitz D, Jeworowski LM, Richter A, Schmidt ML, Schwarz T, Mueller MA, Drosten C, Wendisch D, Sander LE, Osterrieder N, Wilson IA, Pruess H. A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model. Cell .2020 Nov 12;183(4):1058-1069.e19. doi: 10.1016/j.cell.2020.09.049. Epub 2020 Sep 23.

3: Reed E, Hedström AK, Hansson M, Mathsson-Alm L, Brynedal B, Saevarsdottir S, Cornillet M, Jakobsson PJ, Holmdahl R, Skriner K, Serre G, Alfredsson L, Rönnelid J, Lundberg K. Presence of autoantibodies in “seronegative” rheumatoid arthritis associates with classical risk factors and high disease activity. Arthritis Res Ther. 2020 Jul 16;22(1):170. doi: 10.1186/s13075-020-02191-2. PMID: 32678001; PMCID: PMC7364538.

4: Jenning M, Marklein B, Ytterberg J, Zubarev RA, Joshua V, van Schaardenburg D, van de Stadt L, Catrina AI, Nonhoff U, Häupl T, Konthur Z, Burmester GR, Skriner K. Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production. Ann Rheum Dis. 2020 Sep;79(9):1194-1202. doi: 10.1136/annrheumdis-2019-216919. Epub 2020 Jun 12. PMID: 32532752.

5: Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different hierarchies of anti-modified protein autoantibody reactivities in rheumatoid arthritis. Arthritis Rheumatol. 2020 Jun 5. doi: 10.1002/art.41385. Epub ahead of print. PMID: 32501655.

6: Westerlind H, Rönnelid J, Hansson M, Alfredsson L, Mathsson-Alm L, Serre G, Cornillet M, Holmdahl R, Jakobsson PJ, Skriner K, Klareskog L, Saevarsdottir S, Askling J. Anti-citrullinated protein antibody specificities, rheumatoid factor isotypes and incident cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheumatol. 2020 May 31. doi: 10.1002/art.41381. Epub ahead of print. PMID: 32475073.

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