Clinical trial NCT01200979: Assessment of Alterations in Immune Function During Pregnancy and Post Parturition
Official title: Assessment of Alterations in Immune Function During Pregnancy and Post Parturition
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pregnancy Immune Function
Keywords: Gene Expression
IN VITRO
Immunosuppression
Infection
Neutrophils
Pregnancy
Immune Function
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2010-09-14
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE

Brief summary: Traditionally, it has been suggested that pregnancy causes an immunosuppressive state that would facilitate fetal tolerance and result in an increased susceptibility to infection. Although the suppression has been characterized as a global T-cell defect, the observation that the increase in susceptibility is restricted only to specific intracellular bacteria and viruses is consistent with a down regulation of only certain components of the innate immune system. Progress in the treatment and management of infections during pregnancy will require further understanding of the changes to the immune system that occur during pregnancy. It is hypothesized that there is a fundamental down-regulation in the innate immune system that occurs during pregnancy and remains until delivery and that changes in serum cytokines influence na(SqrRoot) ve CD4 differentiation to different subpopulations. To that end, this study will evaluate blood samples drawn from pregnant women during early, mid, and late pregnancy and post-partum for changes in the innate immune system and compare them to those of healthy, non-pregnant women. Changes in the cytokine profile and in the lymphocyte and natural killer (NK) cell populations will be identified. A comparison of any observed changes will be made with those previously reported for in vitro and in vivo studies.

Detailed description: Traditionally, it has been suggested that pregnancy causes an immunosuppressive state that would facilitate fetal tolerance and result in an increased susceptibility to infection. Although the suppression has been characterized as a global T-cell defect, the observation that the increase in susceptibility is restricted only to specific intracellular bacteria and viruses is consistent with a down regulation of only certain components of the innate immune system. Progress in the treatment and management of infections during pregnancy will require further understanding of the changes to the immune system that occur during pregnancy. It is hypothesized that there is a fundamental down-regulation in the innate immune system that occurs during pregnancy and remains until delivery and that changes in serum cytokines influence na(SqrRoot) ve CD4 differentiation to different subpopulations. To that end, this study will evaluate blood samples drawn from pregnant women during early, mid, and late pregnancy and post-partum for changes in the innate immune system and compare them to data on a similar cohort of women of childbearing age from an existing database of healthy, non-pregnant women. Changes in the cytokine profile, gene expression by microarray, and in the lymphocyte and natural killer (NK) cell populations will be identified. We may perform neutrophil analysis. We will evaluate toll-like receptors functionality, and any changes in PBMC throughout pregnancy.

We also plan to evaluate serum cytokine panels, PBMC by flow cytometry, and PBMC for microarray of gene expression, before and after administration of the influenza vaccine in up to 20 of the 40 pregnant subjects. Antibody levels will be measured as well.

A comparison of any observed changes will be made with those previously reported for in vitro and in vivo studies.

Eligibility criteria: * INCLUSION CRITERIA:

All pregnant study subjects must:

* Be between the ages of 18-45 years old.
* Have a positive pregnancy test (urine).
* Be of an estimated gestational age of between 10 and 20 weeks either by ultrasound or LMP.
* Have an identified primary care provider for the pregnancy.
* Be willing to sign the collaborative study consent form from CHI.
* Be willing to have samples collected and stored for future research and immunological studies
* Be willing to sign the collaborative study consent form for normal volunteers from CHI

Up to twenty pregnant subjects who agree to receive the seasonal influenza vaccine must:

* Have no history of allergic reaction to the vaccine or its contents
* Not have received the vaccine from other providers this flu season
* Agree to have an additional 20cc of blood drawn at both Day +1 and Day +7 post-vaccine for immune analysis.

EXCLUSION CRITIERIA:

A subject will be excluded if she:

* Has an identified underlying chronic medical condition that may adversely affect the immune system (e.g., autoimmune, HIV, or hematologic) or the need for immunomodulating medications (e.g., oral steroids) within 30 days prior to conception for a suspected immune disorder. Oral steroid use for any other reason must have been discontinued for at least 30 days prior to participation.
* Is found to have a Hemoglobin reading of less than 8g/dL.
* Has any other medical condition which, in the opinion of the Principal Investigator, poses an unacceptable risk to the subject s participation in the study.

Primary outcomes:
measure: Changes in lymphocyte and NK cell populations during pregnancy compared to non-pregnant control samples.
timeFrame: 1st, 2nd, and 3rd trimesters and postpartum and postpartum
measure: Changes in Cytokine profiles during pregnancy
timeFrame: 1st, 2nd, and 3rd trimesters and postpartum and postpartum
measure: Functionality of Toll-like receptors and changes in gene expression
timeFrame: 1st, 2nd, and 3rd trimesters and postpartum and postpartum
Secondary outcomes:
measure: Functionality of Toll-like receptors and changes in gene expression
timeFrame: Before and after the administration of the influenza vaccine in a subset of pregnant women
measure: Changes in lymphocyte and INK cell populations
timeFrame: Before and after the administration of the influenza vaccine in a subset of pregnant women
measure: Changes in Cytokine profiles
timeFrame: Before and after the administration of the influenza vaccine in a subset of pregnant women
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Christa S Zerbe, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pejcic-Karapetrovic B, Gurnani K, Russell MS, Finlay BB, Sad S, Krishnan L. Pregnancy impairs the innate immune resistance to Salmonella typhimurium leading to rapid fatal infection. J Immunol. 2007 Nov 1;179(9):6088-96. doi: 10.4049/jimmunol.179.9.6088.
citation: Luppi P. How immune mechanisms are affected by pregnancy. Vaccine. 2003 Jul 28;21(24):3352-7. doi: 10.1016/s0264-410x(03)00331-1.
citation: Zhao J, Lei Z, Liu Y, Li B, Zhang L, Fang H, Song C, Wang X, Zhang GM, Feng ZH, Huang B. Human pregnancy up-regulates Tim-3 in innate immune cells for systemic immunity. J Immunol. 2009 May 15;182(10):6618-24. doi: 10.4049/jimmunol.0803876.