Serum markers of B-cell activation in pregnant women with atopic asthma

Abstract

Problem: As maternal atopy represents a risk factor for the development of atopy in offspring, we aimed to assess how pregnancy affects B-cell activation markers in women with atopic asthma and whether they correlate with risk manifestations for allergy in newborns from mothers with atopic asthma.

Method of study: Pregnant women with atopic asthma (AP) in the third trimester of gestation and nonpregnant women with atopic asthma (ANP) were prospectively recruited and compared to respective healthy counterparts (HP and HNP). All pregnant women were also assessed during the postpartum period until 6 weeks after delivery (HP/PP and AP/PP). Newborns were clinically evaluated at the age of 6 months. Peripheral blood samples were taken from each woman at each time point. Soluble CD23 (sCD23), B-cell activating factor (BAFF), IgA, IgG, IgM, kappa (κ), and lambda (λ) free light chains (FLC) were quantified in serum samples.

Results: The AP group presented increased sCD23 (p < 0.05) and BAFF (p < 0.001) levels compared to the ANP group and even higher levels of sCD23 during the postpartum period (p < 0.001). Moreover, the cutoffs of 6.74 g/L for IgG (sensitivity 90.9%, specificity 77.8%) and of 11.30 mg/L for λ FLC (sensitivity 81.8%, specificity 88.9%) in the AP group were predictive factors for the manifestation of allergy in their offspring.

Conclusions: After delivery, the dynamics of sCD23 and BAFF changed significantly in the AP group. Furthermore, we found novel predictive factors for allergy manifestations in the children of these women, with potential clinical application.

Keywords: B-cell activating factor; allergy; asthma; free light chain; immunoglobulins; postpartum; pregnancy; soluble CD23.

FIGURE 1

Box (median with IQR) and whisker (10th and 90th percentiles), and before‐after plots of sCD23 serum levels in the peripheral blood of healthy nonpregnant women and those with atopic asthma (HNP and ANP), during the third trimester of pregnancy (HP and AP), and during the postpartum period at least 6 weeks after delivery (HP/PP and AP/PP). Differences between unpaired and paired groups were tested using the Mann‐Whitney U‐test or Wilcoxon signed‐rank test, respectively (A). Correlations between sCD23 serum levels and CD24^HiCD27⁺ B‐cells (B), CD24^HiCD38^Hi B‐cells (C) and IL‐10 secreting B‐cells (D) in ANP women. For (B), (C) and (D), Spearman correlation coefficients, 95% confidence intervals, and p‐values are indicated. HNP: n = 35; HP: n = 43; HP/PP: n = 42; ANP: n = 32; AP: n = 20; AP/PP: n = 12. *p‐value <0.05; **p‐value <0.01; ***p‐value <0.001. Shaded areas represent normal range. All data regarding healthy women was adapted from Lima et al.

FIGURE 2

Box (median with IQR) and whisker (10th and 90th percentiles), and before‐after plots of BAFF serum levels in the peripheral blood of healthy nonpregnant women and those with atopic asthma (HNP and ANP), during the third trimester of pregnancy (HP and AP), and during the postpartum period at least 6 weeks after delivery (HP/PP and AP/PP). Differences between unpaired and paired groups were tested using the Mann‐Whitney U‐test or Wilcoxon signed‐rank test, respectively (A). Correlation between BAFF serum levels and CD24^HiCD27⁺ B‐cells (B), CD24^HiCD38^Hi B‐cells (C) and IL‐10 secreting B‐cells (D) in AP women. For (B), (C) and (D), Spearman correlation coefficients, 95% confidence intervals, and P‐values are indicated. HNP: n = 35; HP: n = 43; HP/PP: n = 43; ANP: n = 32; AP: n = 20; AP/PP: n = 12. *p‐value <0.05; **p‐value <0.01; ***p‐value <0.001. Shaded areas represent normal range. All data regarding healthy women were adapted from Lima et al.

FIGURE 3

Box (median with IQR) and whisker (10th and 90th percentiles), and before‐after plots of total serum levels of (A) IgA, (B) IgG, (C) IgM, (D) κ FLC, (E) λ FLC, and (F) k/λ FLC ratio in the peripheral blood of healthy nonpregnant women and those with atopic asthma (HNP and ANP), during the third trimester of pregnancy (HP and AP), and during the postpartum period at least 6 weeks after delivery (HP/PP and AP/PP). Differences between unpaired and paired groups were tested using the Mann‐Whitney U‐test or Wilcoxon signed‐rank test, respectively. HNP: n = 35; HP: n = 43 (n = 42 in IgA); HP/PP: n = 43 (n = 42 in IgA); ANP: n = 32; AP: n = 20; AP/PP: n = 12. *p‐value <0.05; **p‐value <0.01; ***p‐value <0.001. Shaded areas represent normal range. All data regarding healthy women was adapted from Lima et al.