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Interferon-γ–inducible protein p16. a new target of antinuclear antibodies in patients with systemic lupus erythematosus
Authors:Hans Peter Seelig  Hans Ehrfeld  Manfred Renz
Abstract:Objective. To determine the cellular expression and localization of interferon-γ (IFNγ)–inducible protein p16, a new antigen specificity of antinuclear antibodies (ANA), and to evaluate the prevalence of anti-p16, particularly in SLE patients. Methods. Serum levels of anti-p16 were determined by immunoblotting with recombinant p16 and cellular p16 messenger RNA (mRNA) by Northern blotting. We also utilized immunoprecipitation of 35Smethionine–labeled proteins, immunostaining of blotted proteins of subcellular fractions, and immunofluorescence studies with affinity-purified rabbit and human anti–recombinant p16. Results. Protein p16 was localized within the nucleolus and nucleoplasm and constitutively expressed in Raji, HeLa, HEp-2, K562, and HL-60 cells. Synthesis of mRNA and protein was increased in the presence of IFNγ. The prevalence of anti-p16 was 29% in 374 SLE patients (35% in those positive for anti–double-stranded DNA) and 0% in 188 healthy individuals. Anti-p16 was always accompanied by positive findings on indirect immunofluorescence for ANA. Conclusion. Anti-p16 represents a main ANA specificity. Anti-p16 may help to elucidate IFNγ-dependent nuclear processes and to link autoantibody production to states of IFNγ activation.
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