Abstract Number: OC 55.1
Meeting: ISTH 2021 Congress
Background: The immune response to FVIII is polyclonal and consists of the production of IgG antibodies (IgG1, IgG2, IgG3, IgG4). Previous findings suggest that a switch from IgG1 to other subclasses is detectable in patients who develop persistent inhibitors.1 A longitudinal analysis of the IgG subclass profile over 6 months post inhibitor development in previously untreated patients (PUPs) reported IgG2 as the only subclass that could be considered a hallmark of inhibitor persistence.2
Aims: To investigate how the anti-FVIII IgG subclass profile evolves along FVIII exposure and whether there is any subclass that has a particular signature in persistent inhibitors.
Methods: From the SIPPET cohort3, 20 PUPs with severe haemophilia A who developed inhibitors and had available plasma samples at baseline, 5 exposure days (EDs), 10 EDs, 20 EDs, and 50 EDs were included in this analysis (Figure 1.A). Inhibitors were characterised based on persistence (Figure 1.B). Transient inhibitors were defined as those tolerised endogenously within 6 months of development and persistent inhibitors were those remaining at 6 months. Anti-FVIII IgG subclasses were measured with an ELISA assay as reported previously2.
Results: All 20 patients had developed inhibitors by 20 EDs (T3). IgG1, IgG3, and IgG4 antibody profiles did not allow to distinguish between transient and persistent inhibitors along the first 50 EDs to FVIII. IgG2 was the only subclass that distinguished persistent inhibitors from transient ones, in that IgG2 antibodies started to appear only in the persistent inhibitor group from inhibitor development onwards (Figure 2).
Conclusions: This is the first longitudinal analysis along FVIII exposure in the SIPPET cohort suggesting that the detection of the anti-FVIII IgG2 subclass during the first 50 EDs is a hallmark of inhibitor persistence.
To cite this abstract in AMA style:Miri S, Valsecchi C, Schiavone L, El-Beshlawy A, Elalfy M, Ramanan V, Eshghi P, Hanagavadi S, Varadarajan R, Karimi M, Rosendaal FR, Mannucci PM, Peyvandi F. IgG2 as Hallmark of Inhibitor Persistence in a Longitudinal Analysis of PUPs in the First 50 Exposure Days to FVIII [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/igg2-as-hallmark-of-inhibitor-persistence-in-a-longitudinal-analysis-of-pups-in-the-first-50-exposure-days-to-fviii/. Accessed September 24, 2021.
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