Oleshko, Olga and Werwitzke, Sonja and Klingberg, Annika and Witte, Torsten and Eichler, Hermann and Klamroth, Robert and Holstein, Katharina and Hart, Christina and Pfrepper, Christian and Knoebl, Paul and Greil, Richard and Neumeister, Peter and Reipert, Birgit M. and Tiede, Andreas (2023) Targets of autoantibodies in acquired hemophilia A are not restricted to factor VIII: data from the GTH-AH 01/2010 study. BLOOD ADVANCES, 7 (1). pp. 122-130. ISSN 2473-9529, 2473-9537
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The root cause of autoantibody formation against factor VIII (FVIII) in acquired hemophilia A (AHA) remains unclear. We aimed to assess whether AHA is exclusively associated with autoantibodies toward FVIII or whether patients also produce increased levels of autoantibodies against other targets. A case-control study was performed enrolling patients with AHA and age-matched controls. Human epithelial cell (HEp-2) immunofluorescence was applied to screen for antinuclear (ANA) and anticytoplasmic autoantibodies. Screening for autoantibodies against extractable nuclear antigens was performed by enzyme immunoassay detecting SS-A/Ro, SS-B/La, U1RNP, Scl-70, Jo-1, centromere B, Sm, double stranded DNA, and alpha-fodrin (AF). Patients with AHA were more often positive for ANA than control patients (64% vs 30%; odds ratio [OR] 4.02, 1.98-8.18) and had higher ANA titers detected than controls. Cytoplasmic autoantibodies and anti-AF immunoglobulin A autoantibodies were also more frequent in patients with AHA compared with controls. Autoantibodies against any target other than FVIII were found in 78% of patients with AHA compared with 46% of controls (OR 4.16, 1.98-8.39). Results were similar preforming sensitivity analyses (excluding either subjects with autoimmune disorders, cancer, pregnancy, or immunosuppressive medication at baseline) and in multivariable binary logistic regression. To exclude that autoantibody staining was merely a result of cross reactivity of anti-FVIII autoantibodies, we tested a mix of 7 well-characterized monoclonal anti-FVIII antibodies. These antibodies did not stain HEp-2 cells used for ANA detection. In conclusion, a diverse pattern of autoantibodies is associated with AHA, suggesting that a more general breakdown of immune tolerance might be involved in its pathology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTI-FACTOR-VIII; ANTINUCLEAR ANTIBODIES; NATURAL ANTIBODIES; AUTOIMMUNITY; DISEASES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 12:51 |
| Last Modified: | 30 Jan 2024 12:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60650 |
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