Th17-related cytokines in systemic lupus erythematosus patients with dilated cardiomyopathies: a possible linkage to parvovirus B19 infection

Abstract

Dilated cardiomyopathies (DCM) are a major cause of mortality in patients with systemic lupus erythematosus (SLE). Immune responses induced by human parvovirus B19 (B19) are considered an important pathogenic mechanism in myocarditis or DCM. However, little is known about Th17-related cytokines in SLE patients with DCM about the linkage with B19 infection. IgM and IgG against B19 viral protein, and serum levels of Th17-related cytokines were determined using ELISA in eight SLE patients with DCM and six patients with valvular heart disease (VHD). Humoral responses of anti-B19-VP1u and anti-B19-NS1 antibody were assessed using Western blot and B19 DNA was detected by nested Polymerase Chain Reaction (PCR). Levels of interleukin (IL)-17, IL-6, IL-1β, and tumor necrosis factor (TNF)-α were significantly higher in SLE patients with DCM (mean ± SEM, 390.99±125.48 pg/ml, 370.24±114.09 pg/ml, 36.01±16.90 pg/ml, and 183.84±82.94 pg/ml, respectively) compared to healthy controls (51.32±3.04 pg/ml, p<0.001; 36.88±6.64 pg/ml, p<0.001; 5.39±0.62 pg/ml, p<0.005; and 82.13±2.42 pg/ml, p<0.005, respectively). Levels of IL-17 and IL-6 were higher in SLE patients with DCM versus those with VHD (both p<0.01). Five (62.5%) of DCM patients had detectable anti-B19-NS1 IgG and four (50.0%) of them had anti-B19-VP1u IgG, whereas only one (16.7%) of VHD patients had detectable anti-B19-NS1 IgG and anti-B19-VP1u IgG. Serum levels of IL-17, IL-6 and IL-1β were markedly higher in SLE patients with anti-B19-VP1u IgG and anti-B19-NS1 IgG compared to those without anti-B19-VP1u IgG or anti-B19-NS1 IgG, respectively. These suggest a potential association of B19 with DCM and Th17-related cytokines implicated in the pathogenesis of DCM in SLE patients.

Figure 1. Serum levels of (A) IL-17, (B) IL-6, (C) IL-1β, and (D) TNF-α in eight patients with systemic lupus erythematosus (SLE) complicated with dilated cardiomyopathy (DCM) and six SLE patients with valvular heart disease (VHD).

The data are presented as dot-plot diagrams with mean ± SEM.

Figure 2. The difference in the levels of IL-17, IL-6, IL-1β and TNF-α (A) between SLE patients with anti-B19-VP1u IgG [VP1u (+)] and without anti-B19-VP1u IgG [VP1u (−)], and (B) between SLE patients with anti-B19-NS1 IgG [NS1 (+)] and without anti-B19-NS1 IgG [NS1(−)].

Data are presented as mean ± SEM. *p<0.05, **p<0.01, ***p<0.005, versus SLE patients without anti-B19-VP1u IgG or anti-B19-NS1 IgG.