Objective: To address key aspects of anti-histone autoimmunity in systemic lupus erythematosus (SLE), we performed a detailed characterization of cellular and humoral autoreactivity to histone H1 and the four core histones H2A, H2B, H3, H4 in patients with SLE and healthy controls.
Methods: Peripheral blood mononuclear cells of 41 SLE patients and 28 healthy controls were exposed to individual histones and proliferation was measured by [3H]-thymidine incorporation. H1-reactive T-cell clones were drawn by limiting dilution. Cytokines and total IgG in culture supernatants was measured by ELISA, autoantibodies to histones were determined by ELISA and immunoblotting.
Results: Proliferative responses to H1 were more frequent and more pronounced in cell cultures from SLE patients (p<0.002), while among the core histones only the response to H2A was increased in patient cultures (p<0.01). All histones elicited a Th1-like cytokine response both in patients and controls (high IFNγ and TNFα, no IL-4) with H1 inducing the highest levels of TNFα. However, H1 stimulated production of IgG and anti-histone antibodies only in cell cultures derived from SLE patients. H1-specific T-cell clones from patients and controls showed a CD4+CD28+ phenotype and a Th1 cytokine profile. Anti-histone antibodies were detected in 51% of SLE patients, were primarily directed to H1, H3 and H4 and predominantly of the IgG2 subtype.
Conclusion: Histone H1 constitutes a major B-cell and T-cell autoantigen in SLE triggering a proinflammatory Th1 response and driving autoantibody production. This suggests that histone H1 may be of considerable relevance for the pathogenesis of SLE.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.