[Auto-immune manifestations in Non-Hodgkin's lymphoma].
OBJECTIVE
A wide spectrum of auto-immune manifestations is frequently reported in non-Hodgkin's lymphoma (NHL). The purpose of the review is to describe the immune manifestations observed in NHL, according to their histological subtype and to discuss the current physiopathological hypothesis with their therapeutic relevance.


BACKGROUND
Most of the organs can be targeted by an immune process due to the lymphoproliferative disease: they include skin diseases (paraneoplastic pemphigus, vasculitis, urticaria, acrosyndromes), peripheral and central nervous system involvement (polyneuropathy, multifocal neuropathy), haematological manifestations (immune cytopenia, acquired bleeding disorders), rheumatologic diseases (arthritis, systemic vasculitis, myositis) and renal lesion (cryoglobulinemia, glomerulopathies). A higher prevalence of autoantibodies, such as antinuclear antibodies, Antiphospholipid antibodies, or endomysium antibodies, is observed in NHL but usually without clinical manifestations. In B-cell NHL, clinical and biological immune manifestations are more frequently observed in indolent lymphoma than in aggressive NHL. In T-cell NHL, immune manifestations are frequent and polymorphous, preceding usually the diagnosis of lymphoma. The prognosis value of the immune manifestations in NHL is unclear. Immune manifestations can be also be related to the treatment procedure, including fludarabine, Interferon, autograft or Rituximab. The physiopathology of the immune manifestations may involve auto-antibodies production by natural CD5+ autoreactive B-cell from which is issue the proliferation, a lost of immune tolerance, an abnormality in the Fas/Fas Ligand pathway or a chronic antigenic stimulation.


CONCLUSIONS
As observed in T-cell lymphoma cases, immunosuppressive treatment can control both immune manifestations and lymphoproliferation, suggesting that lymphoma and auto-immunity may be the two aspects of the same process. The monoclonal antibody anti-CD20 (rituximab), able to suppress the tumoral cells and change the B-cell repertoire is the most promising treatment to cure immune disorders related to NHL. So far, rituximab has been successfully used in mixed cryoglobulinemia and cold agglutinins secondary to NHL.
Département d'hématologie clinique et groupe d'étude des syndromes lymphoprolifératifs, Inserm U164, centre Henri-Becquerel, 76000 Rouen, France. fabrice.jardin@rouen.fnclcc.fr
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D000974:Antibodies, Antinuclear / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015551:Autoimmunity; D006402:Hematologic Diseases / Q000276:immunology; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology*; D009422:Nervous System Diseases / Q000276:immunology; D012216:Rheumatic Diseases / Q000276:immunology; D000069283:Rituximab; D012871:Skin Diseases / Q000276:immunology
D000974:Antibodies, Antinuclear; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab