Mondini Michele, Vidali Matteo, De Andrea Marco, Azzimonti Barbara, Airò Paolo, D'Ambrosio Roberta, Riboldi Piersandro, Meroni Pier Luigi, Albano Emanuele, Shoenfeld Yehuda, Gariglio Marisa, Landolfo Santo
Medical School of Turin, Turin, and Medical School of Piemonte Orientale, Novara, Italy.
Arthritis Rheum. 2006 Dec;54(12):3939-44. doi: 10.1002/art.22266.
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.
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.
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.
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.
研究系统性硬化症（SSc）、系统性红斑狼疮（SLE）及其他自身免疫性疾病中抗干扰素诱导基因IFI16自身抗体的存在情况及其临床意义。
采用免疫组织化学分析评估从SSc患者和SLE患者获取的皮肤活检标本中IFI16的表达。通过酶联免疫吸附测定法测定82例SSc患者和100例SLE患者血清中抗IFI16抗体的水平。还对其他自身免疫性疾病如原发性干燥综合征（SS）、类风湿关节炎（RA）、慢性荨麻疹和丙型肝炎病毒（HCV）感染进行了检测。
IFI16的表达显著增加，在SLE患者和SSc患者的病变皮肤的表皮各层及真皮炎症浸润中均普遍存在。与正常对照组相比，SLE患者、原发性SS患者和SSc患者的抗IFI16 IgG抗体水平显著更高（SLE患者，P<0.002；原发性SS患者，P<0.001；SSc患者，P<0.0005）。在26%的SLE患者、50%的原发性SS患者和21%的SSc患者（局限性皮肤型SSc[lcSSc]患者中的28%与弥漫性皮肤型SSc[dcSSc]患者中的4%）中观察到抗IFI16滴度高于对照受试者的第95百分位数。相比之下，RA患者中抗IFI16的患病率为4%，慢性荨麻疹患者中为5%，HCV感染患者中为13%。
本研究结果提供了证据表明一种干扰素诱导基因IFI16可能参与了诸如SSc等结缔组织疾病的病理生理机制。此外，还证明了与lcSSc有严格相关性，从而为lcSSc与dcSSc的鉴别诊断提供了一种新工具。
