High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis

Area of Science:

• Immunology
• Nephrology
• Pathogenesis of Autoimmune Diseases

Background:

• Systemic lupus erythematosus (SLE) is an autoimmune disease with potential renal involvement, known as lupus nephritis (LN).
• Previous research indicates a correlation between elevated serum type I interferon (IFN) levels and the presence of LN.

Purpose of the Study:

• To investigate the association between serum IFN activity and specific subtypes of lupus nephritis.
• To examine renal tissues and cells to elucidate the role of IFN in LN pathogenesis.

Main Methods:

• Studied 221 patients with SLE, measuring serum IFN activity using WISH bioassay.
• Utilized mRNA in situ hybridization on renal tissues to assess the expression of IFN-induced gene IFIT1 and pDC marker CLEC4C.
• Measured podocyte cell line gene expression via real-time PCR.

Main Results:

• High serum IFN was significantly associated with increased prevalence of class III/IV LN (OR 5.40, P=0.009).
• Type I IFN emerged as a stronger predictor for class III/IV LN than C3 or anti-dsDNA antibodies.
• IFIT1 expression was elevated in all LN classes, most prominently in active class III/IV glomerular areas; IFN directly activated podocytes.

Conclusions:

• Elevated systemic type I IFN plays a role in the pathogenesis of severe lupus nephritis.
• The IFN signature's localization in glomeruli, not pDCs, suggests a potential systemic source of IFN in LN kidneys.