Interferon‐γ–inducible protein p16. a new target of antinuclear antibodies in patients with systemic lupus erythematosus

Abstract

Objective. To determine the cellular expression and localization of interferon-? (IFN 7)-inducible protein p16, a new antigen specificity of antinuclear antibodies (ANA), and to evaluate the prevalence of antip16, particularly in SLE patients.Methods. Serum levels of anti-pl6 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 IFNy. The prevalence of anti-pl6 was 29% in 374 SLE patients (35 % in those positive for anti-double-stranded DNA) and 0% in 188 healthy individuals. Anti-pl6 was always accompanied by positive findings on indirect immunofluorescence for ANA. Conclusion.Anti-pl6 represents a main ANA specificity. Anti-pl6 may help to elucidate IFNydependent nuclear processes and to link autoantibody production to states of IFNy activation.

The HIN-200 family: More than interferon-inducible genes?

“…Clinical symptoms in the human vary extensively and diagnostic criteria include skin rashes, nephritis, arthritis, and lymphopenia [89]. High titer anti-IFI 16 antibodies were detected in the sera of 28.7% (107 of 374) SLE patients but not in healthy controls [90]. Additional experimentation is required to determine if IFI 16 joins HLA, Fcg receptor, and complement as candidate human genes contributing to SLE.…”

Interleukin-6 Induces Expression of Ifi202, an Interferon-inducible Candidate Gene for Lupus Susceptibility

“…Proteins encoded by the 200-gene family share at least one repeat of a partially conserved 200-amino acid domain (20,21). Interestingly, autoantibodies to the IFI16 protein were detected in sera of SLE patients (23), and increased expression of myeloid nuclear differentiation antigen was detected in PBMCs of arthritis patients (24), raising the possibility that increased expression of the p200 family proteins contributes to the development of autoimmune diseases, including SLE.…”

Mislocalization of the interferon inducible protein IFI16 by environmental insults: Implications in autoimmunity

“…Overexpression of IFI16 drives early steps of an inflammatory response through NF-kB mediated secretion of proinflammatory molecules such as ICAM1, E-selectin, IL-8 and MCP-1 [14,15]. Autoantibodies against IFI16 are present in the sera of patients with systemic sclerosis (SSc) [16], systemic lupus erythematosus (SLE) [17,18], rheumatoid arthritis (RA) [19,20] and Sjö gren's Syndrome (SS) [19]. Recently, it has also been discovered as serum circulating protein in the same autoimmune diseases [21].…”