Epstein-Barr virus-driven B Cell Proliferation with CD4+ T Cell Expansion: A Lymphomatoid Granulomatosis-like Disease Related to Hyperinterleukin-10 Secretion of Remarkably Favourable Outcome with Rituximab.
Granulomatous lymphomatosis is an Epstein-Barr virus (EBV)-driven B cell proliferation associated with an exuberant CD4(+) T cell reaction with usually histopathological pictures of angiocentrism. So far, the characteristics of CD4(+) T cells in granulomatous lymphomatosis and the mechanism leading to their expansion remain poorly explored. We report a 56-year-old female with a past history of cold agglutinin disease, which was successfully treated with 4 weekly infusions of rituximab. She presented one year later with features of granulomatous lymphomatosis that resulted in severe lung and bone marrow infiltration. We provide evidence that CD4(+) T cell expansion was oligoclonal, involved anergic cells and did not result from an EBV-driven stimulation. Rather, it resulted possibly from a high production of interleukin-10 by immunoblastic EBV-positive B cells. The outcome was remarkably favourable with rituximab and steroids. Our results suggest that an EBV-driven B cell proliferation should be investigated in patients presenting with a CD4(+) T cells alveolitis or other systemic manifestations resulting from a CD4(+) T cell expansion. These features should prompt to introduce an immunosuppressive therapy including steroids and rituximab. Our results deserve further investigations to confirm our pathophysiological hypotheses in CD4(+) T cell expansions associated with EBV-driven B cell proliferations and to assess whether granulomatous lymphomatosis could result from comparable mechanisms.
Service d'Anatomopathologie, AP-HP, Hôpital Saint-Antoine, Paris, France.
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Cervera
Laboratory of Immunology, AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris, France.
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Guihot
Laboratory of Immunology, AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris, France.|Sorbonne Université, UPMC Univ Paris 06, Paris, France.
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Gorochov
Service d'Immunologie, UFR de Médecine, Amiens, France.
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Lassoued
Sorbonne Université, UPMC Univ Paris 06, Paris, France.|Service d'Hématologie, AP-HP, Hôpital Saint-Antoine, Paris, France.|Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Inserm U1170, Institut Gustave Roussy, Villejuif, France.
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Coppo
D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology*; D049109:Cell Proliferation; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008230:Lymphomatoid Granulomatosis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008875:Middle Aged; D000069283:Rituximab / Q000627:therapeutic use
D000970:Antineoplastic Agents; C508609:IL10 protein, human; D016753:Interleukin-10; D000069283:Rituximab