Abstract Number: PB0462
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Basic
Background: Acquired haemophilia A is a rare but severe autoimmune disorder with factor VIII as autoantigen. Hardly any cases of acquired haemophilia B with an immune response against factor IX are reported. Also, in congenital haemophilia A and B, different rates of anti-drug antibodies are known acknowledging different genetic and environmental risk factors, which are not fully understood.
Aims: To analyze the production of cytokines in PBMCs of healthy individuals upon stimulation with FVIII or FIX compared to an autoantigen control.
Methods: Each 1×106 PBMCs from buffy coats of 9 healthy individuals were stimulated with concentrates of FVIII and FIX in the presence of costimulating anti-CD28 antibody. Myelin-oligodendrocyte glycoprotein (MOG) was used as autoantigen control. Concentrations within product groups were adjusted by international units, the MOG control was used in a comparable molar concentration. Following incubation, cytokine-positive cells were measured by flow cytometry. Friedman test or Wilcoxon signed-rank test was used to assess differences between the distributions of the paired groups as appropriate.
Results: Stimulation with different FVIII and FIX concentrates resulted in highly significant differences in cytokine production of monocytes for IL-6, IL-10, and GM-CSF and was lowest for pFVIII pFVIII (medians 7%, 19%, and 1% respectively). Here, values differed significantly from MOG, pFIX, rFIX, and rFIX-Fc. Additionally, rFL-FVIII-2nd resulted in lower amounts of IL-10 positive monocytes as rFIX and rFIX-Fc.
Conclusions: The immune system of healthy individuals reacts differently towards FVIII and FIX, whereas this difference is most prominent for pFVIII. The reason for this is unknown. pFVIII contains vWF but also traces of immunomodulatory molecules which potentially are present in pFIX as well. As pFVIII-stimulation results in a reduction of regulatory as well as pro-inflammatory cytokine production, the impact on an autoimmune response has to be further elucidated.
To cite this abstract in AMA style:
Scatigna S, Orlowski A, Salzmann-Manrique E, Königs C, Schmidt A. Monocytes Show Differences in Cytokine Expression after Stimulation with FVIII Concentrates Compared to FIX or MOG [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/monocytes-show-differences-in-cytokine-expression-after-stimulation-with-fviii-concentrates-compared-to-fix-or-mog/. Accessed March 22, 2024.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/monocytes-show-differences-in-cytokine-expression-after-stimulation-with-fviii-concentrates-compared-to-fix-or-mog/