Human pregnancy is accompanied by modifications in B cell development and immunoglobulin profile
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Authors: Ziegler, K. B.; Muzzio, D. O.; Matzner, F.; Bommer, I.; Ventimiglia, M. S.; Malinowsky, K.; Ehrhardt, J.; Zygmunt, M.; Jensen, F.
Abstract
Though human pregnancy success has been classically linked with a shift into a Th2 immunoglobulin producing cell response, a clear picture concerning B cell development and immunoglobulin profile during human pregnancy is missing. We analyzed in this work the dynamic of different B cell populations in peripheral blood of pregnant women on the first, second and third trimester of pregnancy. As control, age-matched non-pregnant fertile women were included. Additionally, we quantified the levels of immunoglobulin (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE) in the serum of pregnant and non-pregnant women. We observed a significant decrease in the percentages of transitional B cells in peripheral blood of pregnant women as compared to non-pregnant control women. Besides, percentages of naive as well as switched and non-switched memory B cells in peripheral blood of pregnant women were similar to those in non-pregnant control women. Interestingly, although we did not observe differences in the activation status of B cells as well as in the percentages of plasma cells between pregnant and non-pregnant women, we observed significantly higher levels of IgM, IgA, IgG3, more likely natural antibodies, as well IgG4 in serum of pregnant women compared to non-pregnant age matched control women.
Higher Serum Immunoglobulin G3 Levels May Predict the Development of Multiple Sclerosis in Individuals With Clinically Isolated Syndrome
FRONTIERS IN IMMUNOLOGY
Authors: Trend, Stephanie; Jones, Anderson P.; Cha, Lilian; Byrne, Scott N.; Geldenhuys, Sian; Fabis-Pedrini, Marzena J.; Carroll, William M.; Cole, Judith M.; Booth, David R.; Lucas, Robyn M.; Kermode, Allan G.; French, Martyn A.; Hart, Prue H.
Abstract
Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig) G, IgA, IgM, and IgG1-4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein-Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D-3 [25(OH) D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (% IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH) D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of "upstream" to "downstream" IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (% IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (% IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS.