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Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study

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Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study. / Tiede, Andreas; Hofbauer, Christoph J; Werwitzke, Sonja; Knöbl, Paul; Gottstein, Saskia; Scharf, Rüdiger E; Heinz, Jürgen; Groß, Hans-Jürgen; Holstein, Katharina; Dobbelstein, Christiane; Scheiflinger, Fritz; Koch, Armin; Reipert, Birgit M.

In: BLOOD, Vol. 127, No. 19, 12.05.2016, p. 2289-97.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Tiede, A, Hofbauer, CJ, Werwitzke, S, Knöbl, P, Gottstein, S, Scharf, RE, Heinz, J, Groß, H-J, Holstein, K, Dobbelstein, C, Scheiflinger, F, Koch, A & Reipert, BM 2016, 'Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study', BLOOD, vol. 127, no. 19, pp. 2289-97. https://doi.org/10.1182/blood-2015-09-672774

APA

Tiede, A., Hofbauer, C. J., Werwitzke, S., Knöbl, P., Gottstein, S., Scharf, R. E., Heinz, J., Groß, H-J., Holstein, K., Dobbelstein, C., Scheiflinger, F., Koch, A., & Reipert, B. M. (2016). Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study. BLOOD, 127(19), 2289-97. https://doi.org/10.1182/blood-2015-09-672774

Vancouver

Tiede A, Hofbauer CJ, Werwitzke S, Knöbl P, Gottstein S, Scharf RE et al. Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study. BLOOD. 2016 May 12;127(19):2289-97. https://doi.org/10.1182/blood-2015-09-672774

Bibtex

@article{092b42d7492f4081864e0d3788747b7e,
title = "Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study",
abstract = "Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA.",
keywords = "Aged, Aged, 80 and over, Autoantibodies, Disease-Free Survival, Factor VIII, Female, Hemophilia A, Humans, Immunoglobulin A, Male, Middle Aged, Survival Rate, Clinical Trial, Journal Article, Multicenter Study",
author = "Andreas Tiede and Hofbauer, {Christoph J} and Sonja Werwitzke and Paul Kn{\"o}bl and Saskia Gottstein and Scharf, {R{\"u}diger E} and J{\"u}rgen Heinz and Hans-J{\"u}rgen Gro{\ss} and Katharina Holstein and Christiane Dobbelstein and Fritz Scheiflinger and Armin Koch and Reipert, {Birgit M}",
note = "{\textcopyright} 2016 by The American Society of Hematology.",
year = "2016",
month = may,
day = "12",
doi = "10.1182/blood-2015-09-672774",
language = "English",
volume = "127",
pages = "2289--97",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "19",

}

RIS

TY - JOUR

T1 - Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study

AU - Tiede, Andreas

AU - Hofbauer, Christoph J

AU - Werwitzke, Sonja

AU - Knöbl, Paul

AU - Gottstein, Saskia

AU - Scharf, Rüdiger E

AU - Heinz, Jürgen

AU - Groß, Hans-Jürgen

AU - Holstein, Katharina

AU - Dobbelstein, Christiane

AU - Scheiflinger, Fritz

AU - Koch, Armin

AU - Reipert, Birgit M

N1 - © 2016 by The American Society of Hematology.

PY - 2016/5/12

Y1 - 2016/5/12

N2 - Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA.

AB - Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA.

KW - Aged

KW - Aged, 80 and over

KW - Autoantibodies

KW - Disease-Free Survival

KW - Factor VIII

KW - Female

KW - Hemophilia A

KW - Humans

KW - Immunoglobulin A

KW - Male

KW - Middle Aged

KW - Survival Rate

KW - Clinical Trial

KW - Journal Article

KW - Multicenter Study

U2 - 10.1182/blood-2015-09-672774

DO - 10.1182/blood-2015-09-672774

M3 - SCORING: Journal article

C2 - 26912467

VL - 127

SP - 2289

EP - 2297

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 19

ER -