Interferon-gamma-inducible protein p16. A new target of antinuclear antibodies in patients with systemic lupus erythematosus.
OBJECTIVE
To determine the cellular expression and localization of interferon-gamma (IFN gamma)-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 35S-methionine-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 IFN gamma. 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.


CONCLUSIONS
Anti-p16 represents a main ANA specificity. Anti-p16 may help to elucidate IFN gamma-dependent nuclear processes and to link autoantibody production to states of IFN gamma activation.
Seelig
H P
HP
Institute of Immunology and Molecular Genetics, Karlsruhe, Germany.
Ehrfeld
H
H
Renz
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D000939:Epitopes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007371:Interferon-gamma / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011233:Precipitin Tests; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D000939:Epitopes; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; C076700:IFI16 protein, human; D007371:Interferon-gamma