Acquired Hemophilia A in IgG4-Related Disease: Case Report, Immunopathogenic Study, and Review of the Literature.

Autor:	Sanges S; Univ. Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France.; Inserm, Lille, France.; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest, Lille, France.; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), Lille, France., Jeanpierre E; CHU Lille, Institut d'Hématologie Transfusion, Lille, France.; INSERM, U1011, Univ. Lille, U1011-EGID, Institut Pasteur de Lille, Lille, France., Lopez B; CHU Lille, Institut d'Immunologie, Lille, France., Russick J; Centre de recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France., Delignat S; Centre de recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France., Carpentier B; Service d'Hématologie, Hôpital Saint-Vincent, GHICL, Lille, France., Dubois R; CHU Lille, Institut de Pathologie, Lille, France., Dubucquoi S; Univ. Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France.; Inserm, Lille, France.; CHU Lille, Institut d'Immunologie, Lille, France., Guerrier T; Univ. Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France.; Inserm, Lille, France.; CHU Lille, Institut d'Immunologie, Lille, France., Hachulla É; Univ. Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France.; Inserm, Lille, France.; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest, Lille, France.; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), Lille, France., Hatron PY; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest, Lille, France.; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), Lille, France., Paris C; CHU Lille, Institut d'Hématologie Transfusion, Lille, France.; INSERM, U1011, Univ. Lille, U1011-EGID, Institut Pasteur de Lille, Lille, France., Susen S; CHU Lille, Institut d'Hématologie Transfusion, Lille, France.; INSERM, U1011, Univ. Lille, U1011-EGID, Institut Pasteur de Lille, Lille, France., Launay D; Univ. Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France.; Inserm, Lille, France.; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest, Lille, France.; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), Lille, France., Lacroix-Desmazes S; Centre de recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France., Terriou L; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.; CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest, Lille, France.; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), Lille, France.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Dec 18; Vol. 11, pp. 558811. Date of Electronic Publication: 2020 Dec 18 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.558811
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2020 Sanges, Jeanpierre, Lopez, Russick, Delignat, Carpentier, Dubois, Dubucquoi, Guerrier, Hachulla, Hatron, Paris, Susen, Launay, Lacroix-Desmazes and Terriou.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu