Determination of normal human fetal immunoglobulin M levels

Vick, Dan J.; Hogge, W. Allen; Normansell, David E.; Burkett, Barbara; Harbert, Guy M.

doi:10.1128/cdli.2.1.115-117.1995

Cited by 10 publications

(3 citation statements)

References 19 publications

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“…During pregnancy, the fetal serum IgG is originated from the maternal circulation across the placenta. The maternally derived IgG levels decrease gradually and are replaced by those of infant origin (2,9,15), which starts production approximately 6 months after birth, although IgM production starts soon after birth (2,15,17).…”

Section: Discussionmentioning

confidence: 99%

Subclinical Epstein-Barr Virus Primary Infection and Lytic Reactivation Induce Thyrotropin Receptor Autoantibodies

et al. 2019

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Epstein-Barr virus (EBV) is a herpes virus that mainly infects in B lymphocytes and occasionally reactivates lytically. Most individuals have been infected with EBV primarily in their childhood with no symptoms, and the virus persists latently for life. We have previously reported that EBV-infected B cells with thyrotropin receptor autoantibodies (TRAbs) on their surface [TRAb(+) EBV(+) cells] were present in the peripheral blood mononuclear cells (PBMCs) of healthy adult controls and patients with Graves' disease, and that TRAbs released in the culture medium of PBMCs containing TRAb(+) EBV(+) cells by EBV reactivation. EBV lytic reactivation induced the differentiation of host B cells into plasma cells and antibody production. Various autoantibodies have been detected during the acute phase of infectious mononucleosis (IM) that is the symptomatic primary infection of EBV. Therefore, the autoantibody production may be induced by the asymptomatic primary infection. In this study, we examined the presence of TRAb(+) cells, EBV(+) cells, and TRAb(+) EBV(+) cells in PBMCs from 29 healthy or subclinical children without Graves' disease and one cord blood that were divided into six age groups, and also measured plasma TRAb levels. The results obtained demonstrated that low levels of TRAb production occurred with EBV primary infection and lytic reactivation in children without symptoms of IM. Furthermore, the populations of TRAb(+) cells, EBV(+) cells, and TRAb(+) EBV(+) cells were small in the period of primary infection, but they potentially expand with repeated EBV lytic reactivation. This may partly explain why the onset of Graves' disease often occurs in young adults, but rarely in infancy.

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Section: Discussionmentioning

confidence: 99%

Subclinical Epstein-Barr Virus Primary Infection and Lytic Reactivation Induce Thyrotropin Receptor Autoantibodies

et al. 2019

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“…Vertical transmission and maternal blood contamination are unlikely in this sample, as the mother was vaccinated at least 2 weeks prior to delivery, and SARS-COV-2 specific IgA was undetected ( Table 4 ). Fetal tissues are known to make IgM as early as 10–11 weeks of gestation ( 26 ), and this is detectable in fetal blood as early as 13 weeks of gestation ( 27 ), but reference nomograms for fetal IgMs suggestive of fetal infection exist for fetuses > 23 weeks and through term ( 28 ). Differences in infant inflammatory and anti-inflammatory markers were noted between groups ( Table 4 ).…”

Section: Resultsmentioning

confidence: 99%

Examination of cord blood at birth in women with SARS-CoV-2 exposure and/or vaccination during pregnancy and relationship to fetal complete blood count, cortisol, ferritin, vitamin D, and CRP

et al. 2023

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BackgroundSARS-CoV-2 is known to manifest a robust innate immune response. However, little is known about inflammatory influences from maternal SARS-CoV-2 infection or maternal mRNA vaccination upon the fetus. In addition, it is unknown if Vitamin D deficiency influences fetal homeostasis or if an anti-inflammatory mechanism to the development of possible innate cytokines or acute phase reactants by the maternal/fetal dyad, in the form of cortisol elevations, occur. In addition, effects on Complete Blood Count (CBC) are not known.ObjectiveTo evaluate the neonatal acute phase reactants and anti-inflammatory responses after maternal SARS-CoV-2 disease or mRNA vaccination.MethodsSamples and medical records reviews from mother/baby dyads (n = 97) were collected consecutively, and were categorized into 4 groups; no SARS-CoV-2 or vaccination exposure (Control), Vaccinated mothers, maternal SARS-CoV-2 disease positive/IgG titer positive fetal blood, and maternal SARS-CoV-2 positive/IgG titer negative fetal blood. SARS-CoV-2 IgG/IgM/IgA titers, CBC, CRP, ferritin, cortisol, and Vitamin D were obtained to examine the possible development of an innate immune response and possible anti-inflammatory response. Student's t-test, Wilcoxon rank-sum, and Chi-squared with Bonferroni corrections were used to compare groups. Multiple imputations were performed for missing data.ResultsCortisol was higher in babies of both mothers who were vaccinated (p = 0.001) and SARS-CoV-2 positive/IgG positive (p = 0.009) as compared to the control group suggesting an attempt to maintain homeostasis in these groups. Measurements of ferritin, CRP, and vitamin D did not reach statistical significance. CBC showed no variation, except for the mean platelet volume (MPV), which was elevated in babies whose mothers were vaccinated (p = 0.003) and SARS-CoV-2 positive/IgG positive (p = 0.007) as compared to the control group.ConclusionAcute phase reactant elevations were not noted in our neonates. Vitamin D levels were unchanged from homeostatic levels. Cord blood at birth, showed Cortisol and MPV higher in vaccinated and SARS-CoV-2 IgG positive mother/baby dyads as compared to the Control group, indicating that possible anti-inflammatory response was generated. The implication of possible inflammatory events and subsequent cortisol and/or MPV elevation effects upon the fetus after SARS-CoV-2 disease or vaccination is unknown and merits further investigation.

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“…It is well known that there is no transport of IgM across the placenta; however, fetal IgM has been detected in fetal blood from about 13 weeks of gestation 28 . Therefore, high fetal IgM concentrations may suggest an intrauterine infection or immunological stimulation [29][30][31] by viral antigens transported bound to IgG 27 or cross reactivity of low affinity fetal IgM . Cases of possible vertical SARS-CoV-2 transmission are rare, but have been previously reported 13,20,32 .…”

Section: Discussionmentioning

confidence: 99%

Waning of the Humoral Response to SARS-CoV-2 in Pregnancy is Variant-Dependent

Mayo

Raz

David

et al. 2021

Preprint

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ImportanceThe SARS-CoV-2 alpha variant posed increased risk for COVID-19 complications in pregnant women. However, its impact on the maternal humoral response and placental IgG transport remains unclear.ObjectiveTo characterize the maternal humoral waning and neonate immunity acquired during the 3rd COVID-19 wave in Israel, dominated by the Alpha variant, as compared to earlier Wildtype infections and humoral response to vaccination across gestation.DesignMaternal and fetal blood serum were collected at delivery since April 2020 from parturients. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel supplemented with additional HA-coupled microspheres.SettingA nationwide multicenter cohort study on SARS-CoV-2 infections and vaccination during pregnancy.ParticipantsExpectant women presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 primary groups: SARS-CoV-2 positive (n = 157) and fully vaccinated during pregnancy (n = 125), and unvaccinated noninfected controls matched to the infected group by BMI, maternal age, comorbidities and gestational age (n = 212). Eligibility criteria included pregnant women without active COVID-19 disease, age ≥18 years and willingness to provide informed consent.Main Outcome(s) and Measure(s)Pregnant women’s humoral response is dependent on the SARS-CoV-2 strain.ResultsThe humoral response to infection as detected at birth, showed a gradual and significant decline as the interval between infection/vaccination and delivery increased. Significantly faster decay of antibody titers was found for infections occurring during the 3rd wave compared to earlier infections/vaccination. Cord blood IgG antigens levels correlated with maternal IgG. However, cord IgG-HA variance significantly differed in SARS-CoV2 infections as compared to the other groups. No sexual dimorphism in IgG transfer was observed. Lastly, high fetal IgM response to SARS-CoV-2 was detected in 17 neonates, all showing elevated IgM to N suggesting exposure to SARS-Cov-2 antigens.Conclusions and RelevanceInfections occurring during the 3rd wave induced a faster decline in humoral response when compared to Wildtype infections or mRNA BNT162b2 vaccination during pregnancy, consistent with a shift in disease etiology and severity induced by the Alpha variant. Vaccination policies in previously infected pregnant women should consider the timing of exposure along pregnancy as well as the risk of infection to specific variants of concern.Key PointsQuestionWhat is the difference in the maternal-fetal humoral response between Alpha variant and SARS-CoV-2 Wildtype infections?FindingsIn this nationwide multicenter study including 494 pregnant women, the maternal humoral response to Alpha variant infection was weaker and shorter when compared to Wildtype infections. Placental transport compensated for the maternal waning of immunity. Fetal sex did not affect humoral response.MeaningVaccination policies should be adjusted to account for the timing of infection and the SARS-CoV-2 variant.

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Determination of normal human fetal immunoglobulin M levels

Cited by 10 publications

References 19 publications

Subclinical Epstein-Barr Virus Primary Infection and Lytic Reactivation Induce Thyrotropin Receptor Autoantibodies

Subclinical Epstein-Barr Virus Primary Infection and Lytic Reactivation Induce Thyrotropin Receptor Autoantibodies

Examination of cord blood at birth in women with SARS-CoV-2 exposure and/or vaccination during pregnancy and relationship to fetal complete blood count, cortisol, ferritin, vitamin D, and CRP

Waning of the Humoral Response to SARS-CoV-2 in Pregnancy is Variant-Dependent

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