Immunoglobulin G, A, and M responses to BK virus in renal transplantation

Abstract

Immunoglobulin G (IgG), IgA, and IgM antibodies were measured in serum samples from 71 organ donors, 81 kidney transplant recipients at transplantation, and 67 patients during the posttransplant period by using a virus-like particle-based enzyme-linked immunosorbent assay (ELISA). BK virus (BKV) and JC virus DNA were detected in urine and plasma by real-time PCR. IgG antibodies to BKV were demonstrated in the majority (80.3 to 100%) of patients irrespective of clinical category, but titers were highest in patients with active viral replication. IgA antibodies were present with greater frequency (72.7 to 81.3% versus 0 to 23.6%; P < 0.001) and higher titer (mean optical density, 0.11 to 0.15 versus 0.05 to 0.08; P < 0.001) in patients who were BKV DNA positive than those who were BKV DNA negative. IgM antibodies showed a similar pattern of reactivity but lower frequency in the setting of active viral replication (9.1 to 43.7% versus 0 to 1.4%; P < 0.001). A rise in IgG level of >0.577 optical density (OD) units or a rise in IgA or IgM level of >0.041 OD units was strongly associated with active viral replication. Urine viral load showed a positive correlation with IgM titer (r = 0.22) but a negative correlation with IgG titer (r = -0.28) and IgA titer (r = -0.1). Chronic dialysis patients typically did not have serologic or virologic evidence of active BKV infection. Anti-BKV titers did not rise in patients with JC viruria. In conclusion, measurement of anti-BKV antibody titer and class response can be used to detect the onset of viral replication. ELISAs can be quite specific despite considerable sequence homology between BK virus and JC virus.

FIG. 1.

Box plots showing optical density readings in the ELISA for IgG (a), IgA (b), or IgM (c) anti-BKV antibodies in different study categories. Each box plot depicts measurements from the 25th to 75th percentile (SigmaPlot 8.0). The error bars correspond to the 10th and 90th percentiles. The horizontal bar in each box represents the median value. Outliers are indicated by the solid circles. The thick horizontal line indicates the optical density cutoff used to define patients as seropositive or seronegative. Subject categories, with the number of subjects in parentheses, are as follows: donors (71), recipient baseline samples (81), posttransplant BKV PCR negative (21), JCV viruria (19), BKV viruria (11), and BKV viremia (16). Optical densities in lanes 5 and 6 are higher than all other categories (P < 0.05).

FIG. 2.

Box plot showing BKV and JCV viral loads (log transformed) in posttransplant PCR-positive subjects. Subject categories, with the number of subjects in parentheses, are as follows: plasma levels in patients with BKV viremia (16), urinary BKV load in patients with viremia (16), urinary BKV load in patients with asymptomatic viruria but no viremia (11), and JCV DNA load in patients with JC viruria (19). Urinary viral loads were higher in patients with BKV viremia than in patients with BKV viruria or JCV viruria (P < 0.001). The box plot depicts measurements from the 25th to the 75th percentile (SigmaPlot 8.0). The error bars correspond to the 10th and 90th percentiles. The horizontal bar in each box represents the median value. Outliers are indicated by the solid circles.

FIG. 3.

Semilog plot of urinary viral load versus anti-BKV IgG using only samples from patients with active BKV viremia or viruria. The optical density shows a negative correlation with increasing viral load. The linear regression line in the middle is bracketed by two hairlines, which indicate the 95% prediction intervals calculated by SigmaPlot 8.0.