A novel autoantigen to differentiate limited cutaneous systemic sclerosis from diffuse cutaneous systemic sclerosis: the interferon-inducible gene IFI16.
OBJECTIVE
To investigate the presence and clinical significance of autoantibodies against the interferon-inducible gene IFI16 in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and other autoimmune diseases.


METHODS
Immunohistochemical analysis was used to evaluate the expression of IFI16 in skin biopsy specimens obtained from patients with SSc and patients with SLE. Levels of antibodies against IFI16 in sera from 82 patients with SSc and 100 patients with SLE were determined by enzyme-linked immunosorbent assay. Other autoimmune diseases such as primary Sjögren's syndrome (SS), rheumatoid arthritis (RA), chronic urticaria, and hepatitis C virus (HCV) infection were also examined.


RESULTS
Expression of IFI16 was greatly increased and was ubiquitous in all layers of the epidermis and in the dermal inflammatory infiltrates of lesional skin from both patients with SLE and patients with SSc. Patients with SLE, those with primary SS, and those with SSc exhibited significantly higher anti-IFI16 IgG antibody levels compared with normal controls (for SLE, P < 0.002; for primary SS, P < 0.001; for SSc, P < 0.0005). Anti-IFI16 titers above the ninety-fifth percentile for control subjects were observed in 26% of the patients with SLE, 50% of those with primary SS, and 21% of those with SSc (28% of patients with limited cutaneous SSc [lcSSc] versus 4% of patients with diffuse cutaneous SSc [dcSSc]). In contrast, the prevalence of anti-IFI16 was 4% in patients with RA, 5% in those with chronic urticaria, and 13% in those with HCV infection.


CONCLUSIONS
The results of this study provide evidence that an IFN-inducible gene, IFI16, may be involved in the pathophysiologic mechanisms of connective tissue disorders such as SSc. Moreover, a strict correlation with lcSSc was also demonstrated, thus providing a novel tool in the differential diagnosis of lcSSc from dcSSc.
Mondini
Michele
M
Medical School of Turin, Turin, and Medical School of Piemonte Orientale, Novara, Italy.
Vidali
Matteo
M
De Andrea
Marco
M
Azzimonti
Barbara
B
Airò
Paolo
P
D'Ambrosio
Roberta
R
Riboldi
Piersandro
P
Meroni
Pier Luigi
PL
Albano
Emanuele
E
Shoenfeld
Yehuda
Y
Gariglio
Marisa
M
Landolfo
Santo
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000276:immunology* / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology* / Q000378:metabolism; D045743:Scleroderma, Diffuse / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D045745:Scleroderma, Limited / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology; D012867:Skin / Q000378:metabolism / Q000473:pathology
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human