IgG Subclasses and Congenital Transmission of Chagas Disease

Abstract

The mechanism of vertical transmission of Trypanosoma cruzi is poorly understood. In this study, we evaluated the role of IgG subclasses in the congenital transmission of Chagas disease. We conducted a case-control study in a public maternity hospital in Santa Cruz, Bolivia, enrolling women at delivery. Thirty women who transmitted T. cruzi to their newborns (cases), and 51 women who did not (controls) were randomly selected from 676 total seropositive women. Trypanosoma cruzi-specific IgG1, IgG2, and IgG3 levels were measured by in-house ELISA. The IgG4 levels were unmeasurable as a result of low levels in all participants. Quantitative polymerase chain reaction results and demographic factors were also analyzed. One-unit increases in normalized absorbance ratio of IgG1 or IgG2 levels increased the odds of congenital T. cruzi transmission in Chagas-seropositive women by 2.0 (95% CI: 1.1-3.6) and 2.27 (95% CI: 0.9-5.7), adjusted for age and previous blood transfusion. Odds of congenital transmission were 7.0 times higher in parasitemic mothers (95% CI: 2.3-21.3, P < 0.01) compared with nonparasitemic mothers. We observed that all mothers with IgG1 ≥ 4 were transmitters (sensitivity = 20%, specificity = 100%). Additionally, no mothers with IgG2 < 1.13 were transmitters (sensitivity = 100%, specificity = 21.6%). We demonstrated that IgG subclasses and parasite presence in blood are associated with vertical transmission of T. cruzi and could identify women at increased risk for congenital transmission by measuring IgG subclasses. These measures have potential as objective screening tests to predict the congenital transmission of Chagas.

Figure 1.

IgG1 values in mothers who transmitted and those who did not transmit congenitally. All of the mothers with IgG1 ≥ cutoff were transmitters. 1. Differences in IgG1 are significant (P < 0.0003) when comparing mothers with IgG1 ≥ 4 against either transmitters or nontransmitters with IgG1 < 4. Additionally, in contrast with the significant difference in IgG1 values when comparing all transmitters against nontransmitters (Table 2), the difference is not significant after excluding transmitters with IgG1 ≥ 4 (P = 0.3). This figure appears in color at www.ajtmh.org.