Anticytokine autoantibodies in infectious diseases: pathogenesis and mechanisms.
Autoantibodies to cytokines occur in many different conditions and situations and can cause a wide range of disease, including pulmonary alveolar proteinosis, disseminated non-tuberculous mycobacterial disease, pure red-cell aplasia, and chronic mucocutaneous candidiasis. Anticytokine autoantibodies may also develop against exogenously administered cytokines, sometimes diminishing their effects or inhibiting the activity of the endogenous cytokine. Unlike primary congenital immunodeficiencies, autoantibodies may develop over time, wax and wane, and may change in titre or avidity. Naturally occurring autoantibodies to interferons α, β, and γ, interleukins 1α, 2, 6, and 10, tumour necrosis factor, and granulocyte-macrophage colony-stimulating factor have been reported in healthy individuals and have been identified in rheumatological diseases, graft-versus-host disease, and cancer. Therapeutic antibodies, growth factors, other biological agents, and cytokines used to treat acute, chronic, malignant, and immune diseases may elicit or overcome autoantibodies, hence influencing the primary intended therapy. The increasing number of biologically active anticytokine autoantibodies being reported suggests that currently "idiopathic" diseases may someday be explained by neutralising or agonising autoantibodies. Their protean roles in causing, treating, preventing, and responding to disease, as well as simply maintaining normal homoeostasis, offer fascinating insights into the biology of immunity, inflammation, and infection.
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Sarah K
SK
Browne
Steven M
SM
Holland
D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D003115:Colony-Stimulating Factors / Q000276:immunology*; D003141:Communicable Diseases / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D006801:Humans
D001323:Autoantibodies; D003115:Colony-Stimulating Factors; D016207:Cytokines