Acquired Hemophilia A in IgG4-Related ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Title :
Acquired Hemophilia A in IgG4-Related Disease: Case Report, Immunopathogenic Study, and Review of the Literature
Author(s) :
Sanges, Sébastien [Auteur correspondant]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Jeanpierre, Emmanuelle [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Lopez, Benjamin [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Russick, Jules [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Delignat, Sandrine [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Carpentier, Benjamin [Auteur]
Hôpital Saint Vincent de Paul de Lille
Dubois, Romain [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Dubucquoi, Sylvain [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Guerrier, Thomas [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Hachulla, Éric [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Hatron, Pierre-Yves [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Paris, Camille [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Susen, Sophie [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Launay, David [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Lacroix-Desmazes, Sébastien [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Terriou, Louis [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Jeanpierre, Emmanuelle [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Lopez, Benjamin [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Russick, Jules [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Delignat, Sandrine [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Carpentier, Benjamin [Auteur]
Hôpital Saint Vincent de Paul de Lille
Dubois, Romain [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Dubucquoi, Sylvain [Auteur]

Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Guerrier, Thomas [Auteur]

Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Hachulla, Éric [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Hatron, Pierre-Yves [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Paris, Camille [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Susen, Sophie [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Launay, David [Auteur]

Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Lacroix-Desmazes, Sébastien [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Terriou, Louis [Auteur]

Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Journal title :
Frontiers in Immunology
Pages :
558811
Publisher :
Frontiers
Publication date :
2020-12-18
ISSN :
1664-3224
English keyword(s) :
anti-factor VIII autoantibodies
IgG4 antibodies
acquired hemophilia A
IgG4-related disease
plasma cell
IgG4 antibodies
acquired hemophilia A
IgG4-related disease
plasma cell
HAL domain(s) :
Sciences du Vivant [q-bio]/Immunologie/Immunité adaptative
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hématologie
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hématologie
English abstract : [en]
We report the observation of a 75-year-old patient referred for cervical lymphadenopathies. A pre-lymphadenectomy blood work revealed an asymptomatic elevation of aPTT with low factor VIII (FVIII) levels and high anti-FVIII ...
Show more >We report the observation of a 75-year-old patient referred for cervical lymphadenopathies. A pre-lymphadenectomy blood work revealed an asymptomatic elevation of aPTT with low factor VIII (FVIII) levels and high anti-FVIII antibodies titers, consistent with acquired hemophilia A (AHA). Histological work-up of a cervical lymphadenopathy revealed benign follicular hyperplasia with IgG4+ lymphoplasmacytic infiltration; and serum IgG4 levels were markedly elevated, compatible with IgG4-related disease (IgG4-RD). He was successfully treated with a 9-month course of prednisone, secondarily associated with rituximab when an AHA relapse occurred. As this patient presented with an unusual association of rare diseases, we wondered whether there was a link between the two conditions. Our first hypothesis was that the anti-FVIII autoantibodies could be directly produced by the proliferating IgG4+ plasma cells as a result of broken tolerance to autologous FVIII. To test this assumption, we determined the anti-FVIII IgG subclasses in our patient and in a control group of 11 AHA patients without IgG4-RD. The FVIII inhibitor was mostly IgG4, with an anti-FVIII IgG4/IgG1 ratio of 42 at diagnosis and 268 at relapse in our patient; similar values were observed in non-IgG4-RD AHA patients. As a second hypothesis, we considered whether the anti-FVIII activity could be the result of a non-specific autoantibody production due to polyclonal IgG4+ plasma cell proliferation. To test this hypothesis, we measured the anti-FVIII IgG4/total IgG4 ratio in our patient, as well as in several control groups: 11 AHA patients without IgG4-RD, 8 IgG4-RD patients without AHA, and 11 healthy controls. We found that the median [min-max] ratio was higher in AHA-only controls (2.4 10-2 [5.7 10-4-1.79 10-1]), an oligoclonal setting in which only anti-FVIII plasma cells proliferate, than in IgG4-RD-only controls (3.0 10-5 [2.0 10-5-6.0 10-5]), a polyclonal setting in which all IgG4+ plasma cells proliferate equally. Our patient had intermediate ratio values (2.7 10-3 at diagnosis and 1.0 10-3 at relapse), which could plead for a combination of both mechanisms. Although no definitive conclusion can be drawn, we hypothesized that the anti-FVIII autoantibody production in our IgG4-RD AHA patient could be the result of both broken tolerance to FVIII and bystander polyclonal IgG4+ plasma cell proliferation.Show less >
Show more >We report the observation of a 75-year-old patient referred for cervical lymphadenopathies. A pre-lymphadenectomy blood work revealed an asymptomatic elevation of aPTT with low factor VIII (FVIII) levels and high anti-FVIII antibodies titers, consistent with acquired hemophilia A (AHA). Histological work-up of a cervical lymphadenopathy revealed benign follicular hyperplasia with IgG4+ lymphoplasmacytic infiltration; and serum IgG4 levels were markedly elevated, compatible with IgG4-related disease (IgG4-RD). He was successfully treated with a 9-month course of prednisone, secondarily associated with rituximab when an AHA relapse occurred. As this patient presented with an unusual association of rare diseases, we wondered whether there was a link between the two conditions. Our first hypothesis was that the anti-FVIII autoantibodies could be directly produced by the proliferating IgG4+ plasma cells as a result of broken tolerance to autologous FVIII. To test this assumption, we determined the anti-FVIII IgG subclasses in our patient and in a control group of 11 AHA patients without IgG4-RD. The FVIII inhibitor was mostly IgG4, with an anti-FVIII IgG4/IgG1 ratio of 42 at diagnosis and 268 at relapse in our patient; similar values were observed in non-IgG4-RD AHA patients. As a second hypothesis, we considered whether the anti-FVIII activity could be the result of a non-specific autoantibody production due to polyclonal IgG4+ plasma cell proliferation. To test this hypothesis, we measured the anti-FVIII IgG4/total IgG4 ratio in our patient, as well as in several control groups: 11 AHA patients without IgG4-RD, 8 IgG4-RD patients without AHA, and 11 healthy controls. We found that the median [min-max] ratio was higher in AHA-only controls (2.4 10-2 [5.7 10-4-1.79 10-1]), an oligoclonal setting in which only anti-FVIII plasma cells proliferate, than in IgG4-RD-only controls (3.0 10-5 [2.0 10-5-6.0 10-5]), a polyclonal setting in which all IgG4+ plasma cells proliferate equally. Our patient had intermediate ratio values (2.7 10-3 at diagnosis and 1.0 10-3 at relapse), which could plead for a combination of both mechanisms. Although no definitive conclusion can be drawn, we hypothesized that the anti-FVIII autoantibody production in our IgG4-RD AHA patient could be the result of both broken tolerance to FVIII and bystander polyclonal IgG4+ plasma cell proliferation.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Source :
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