Cytomegalovirus-Associated Autoantibody against TAF9 Protein in Patients with Systemic Lupus Erythematosus

Abstract

Background: Evidence indicates a causal link between cytomegalovirus (CMV) infection and the triggering of systemic lupus erythematosus (SLE). Animal studies have revealed that CMV phosphoprotein 65 (pp65) induces autoantibodies against nuclear materials and causes the autoantibody attack of glomeruli. IgG eluted from the glomeruli of CMVpp65-peptide-immunized mice exhibited cross-reactivity against dsDNA and TATA-box-binding protein associated factor 9 (TAF9). Whether the elevation of anti-TAF9 IgG is associated with anti-CMV reactivity in human lupus remains unclear. Methods: The sera from patients with rheumatic diseases, including ankylosing spondylitis (AS), gout, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren syndrome (SS) were examined using ELISA for antibodies of CMV, CMVpp65, and TAF9. Results: In total, 83.8% of the rheumatic patients had acquired CMV infections. The SLE patients had a high prevalence of anti-CMV IgM. The highest seropositivity rates for anti-HCMVpp65 and anti-TAF9 IgG were observed in the SLE patients. Purified anti-CMVpp65 IgG from CMVpp65/TAF9 dual-positive SLE sera reacted to both TAF9 and dsDNA. An increased prevalence of proteinuria and low hemoglobin levels were found in CMV IgG- and CMVpp65 IgG-positive SLE patients. Conclusions: This observation suggests that immunity to CMVpp65 is associated with cross-reactivity with TAF9 and dsDNA and that it is involved in the development of clinical manifestations in SLE.

Keywords: TATA-box-binding protein associated factor 9; anemia; cytomegalovirus phosphoprotein 65; proteinuria; systemic lupus erythematosus.

Figure 1

ELISA analysis of the antibody response to CMV using sera of patients with SLE (n = 193), SS (n = 70), RA (n = 84), gout (n = 92), and AS (n = 68). (A) Anti-CMV IgM activity. (B) Anti-CMV IgG activity. * p  ≤  0.05; ** p  ≤  0.01; *** p  ≤  0.001.

Figure 2

ELISA analysis of the antibody responses to CMVpp65 and TAF9 using sera of patients with SLE (n = 193), SS (n = 70), RA (n = 84), gout (n = 92), and AS (n = 68). (A) Anti-CMVpp65 IgG activity. (B) Anti-human TAF9 IgG activity. * p  ≤  0.05; *** p  ≤  0.001.

Figure 3

Analysis of the correlation between anti-CMVpp65 IgG, anti-human TAF9 IgG, and anti-dsDNA IgG by ELISA testing with anti-CMVpp65 IgG purified from CMVpp65/TAF9 dual-positive SLE sera (n = 28).