Pregnancy induces nonimmunoglobulin insulin-binding activity in both maternal and cord blood serum

Abstract

To evaluate whether pregnancy has any effect on insulin antibody levels and to test the concordance between a conventional radioimmunoassay and a new microassay for the detection of insulin antibodies, insulin antibodies were analysed in 104 mothers in early pregnancy and at delivery and in their newborn infants. Thirty-eight of the mothers had type 1 diabetes. The concordance between the assays was high in the samples taken in early pregnancy (95%), but substantially lower in the samples taken at delivery (40%) and in the cord blood samples (68%). A considerable proportion of the mothers at delivery, especially the unaffected mothers (71%), and the newborn infants of the unaffected mothers (32%) were positive for insulin antibodies in the conventional assay but not in the microassay. Insulin antibody levels increased in the mothers, significantly so in the unaffected mothers (P < 0.001), during pregnancy in the conventional assay, whereas in the microassay they decreased significantly (P < 0.01) in affected mothers and remained negative in the unaffected mothers. Since immune complexes are precipitated with protein A specific for IgG in the microassay and with polyethylene glycol lacking specificity for immunoglobulins in the conventional assay, our data indicate that insulin antibody levels decrease on average during pregnancy and that the increasing non-IgG anti-insulin activity observed in the conventional assay is induced by pregnancy and is present in both the maternal and the foetal circulation.

Figures

Fig. 1

Frequency (%) of IA at the end of the first trimester (▪), at delivery () and in cord blood (□) in women with type 1 diabetes and unaffected women according to the conventional assay (cIAA) and the microassay (mIAA). None of the nondiabetic women tested positive for IAA in early pregnancy according to any assay or at delivery according to the microassay, and none of the newborn infants of the unaffected mothers had IAA according to the microassay. ** P < 0·01, *** P < 0·001.

Fig. 2

IA levels in samples taken from the women at the end of the first trimester (▪) and at delivery () and in the cord blood of newborn infants (□) according to the conventional assay (cIAA; a) and the microassay (mIAA; b). The broken line indicates the cut-off limit for IA positivity (1·56 RU in the mIAA and 68 nU/ml in the cIAA). Each box plot represents the median, and the 25th and 75th percentiles. The error bars represent the lowest and the highest values that are not outliers. Statistical significance evaluated with Wilcoxon's rank-sum test. * P < 0·05, ** P < 0·01, *** P < 0·001.

Fig. 3

Comparison of IA results obtained by the conventional assay (cIAA) and the microassay (mIAA) for samples taken (a) at the end of the first trimester (n = 102) and (b) at delivery (n = 104) and (c) cord blood samples (n = 104). The broken lines indicate the cut-off limit for IA positivity (1·56 RU in the mIAA and 68 nU/ml in the cIAA). Spearman's nonparametric rank correlation analyses gave an rs of 0·72 for samples taken in early pregnancy, 0·64 for samples taken at delivery and 0·55 for cord blood samples (P < 0·001 for all).