Abstract
The association of autoantibodies to cytokines with immune deficiency, autoimmunity and/or immune dysregulation is increasingly being recognized. For example, autoantibodies to interferon gamma have been found to be associated with chronic, treatment refractory infections with intracellular organisms such as mycobacteria, autoantibodies to interleukin 17 with chronic mucocutaneous candidiasis, and anti-interferon alpha autoantibodies with systemic lupus erythematosus. While low titer autoantibodies to these and other cytokines may be detected in normal individuals, patients with infectious or autoimmune manifestations tend to have high titer autoantibodies that may block or potentiate the function of the respective cytokine. Recognition of these autoantibodies is important because it may direct treatment toward a combination of adjunctive immunotherapy to modulate the autoantibody level while continuing with appropriate anti-microbial therapy. This review focuses on the anti-cytokine autoantibodies documented to date, their autoimmune, immune dysregulation and infectious disease associations, methods for detection of these antibodies and potential treatment options.
Highlights
Autoantibodies (AAbs) to cytokines are increasingly being recognized as potential contributors to acquired immune deficiency, immune dysregulation and autoimmunity [1,2,3]
This review focuses on the anti-cytokine AAbs for which there is growing evidence for association with infection (IFNγ, IFNα, IL-6, IL17/22, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)), with immune dysregulation/autoimmune conditions (IL-8, Granulocyte Colony-Stimulating Factor (G-CSF), EPO)
Kisand and colleagues reported on a cohort of 162 patients with APECED and described anti-IL-17A, IL-17F and/or IL-22 AAbs in over 90% of cases, and detected high titer IL-17A and IL-22 AAbs in two patients with thymoma and Chronic mucocutaneous candidiasis (CMC) [30]
Summary
Autoantibodies (AAbs) to cytokines are increasingly being recognized as potential contributors to acquired immune deficiency, immune dysregulation and autoimmunity [1,2,3]. PAP (Pulmonary Alveolar Proteinosis), since GM-CSF orchestrates the maturation and function of pulmonary alveolar macrophages [5,6] In other cases, such as anti-G-CSF AAbs in Felty’s syndrome, the presence of the autoantibody may be an association rather than causative of the disease [7]. There is, growing evidence to suggest that anticytokine AAbs may play a direct pathogenic role in susceptibility to infection, rather than arising as a consequence of the immune response to the organism, including the detection of AAbs before development of the associated infectious disease [14]. There is considerable overlap between these categories because anti-cytokine AAbs may play a role in modulating disease activity in autoimmune conditions, as evidenced by the potentially beneficial role of anti-IFNα AAbs in modulating SLE [19], and may increase susceptibility to infections as has been observed in certain immune deficient patients [20].
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