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Objective The objective is to develop a biorepository of samples that represent all stages of a women’s life. Importantly, our goal is to collect longitudinal physical specimens as well as the associated short and long-term clinical information. Study Design The Women’s Health Tissue Repository was established to encompass four tissue banks: Well Women Tissue Bank, Reproductive Endocrinology & Infertility Tissue Bank, Maternal Fetal Tissue Bank, and the long-established Gynecologic Malignancies Tissue Bank. Based on their health status, women being seen in Women’s Health at the University of Iowa are recruited to contribute samples and grant access to their electronic medical record to the biorepository. Samples are coded, processed, and stored for use by investigators. Results The Maternal Fetal Tissue Bank was the first expansion of our department’s biobanking efforts. Approximately 75% of the women approached consent to participate in the Maternal Fetal Tissue Bank. Enrollment has steadily increased. Samples have been used for over 20 projects in the first 3 years and are critical to 7 funded grants and 3 patent applications. Conclusion Patient samples with corresponding clinical data are initially important to women’s health research. Our model demonstrates that many research projects by faculty, fellows, and residents have benefited from the existence of the Women’s Health Tissue Repository. While challenging to achieve, longitudinal sampling allows for the greatest opportunity to study normal and pathological changes throughout all phases of a women’s life, including pregnancy. This bank facilitates and accelerates the development of novel research, technologies, and possible therapeutic options in women’s health. The establishment of more longitudinal biorepositories based on our model would enhance women’s health research.

The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy, involves imbalanced T helper (T) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in PreE in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of PreE in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human PreE. AVP infusion throughout gestation in mice resulted in increased pro-inflammatory interferon γ (IFNg) (T1) in the maternal plasma. The T17-associated cytokine interleukin (IL)-17 was elevated in the maternal plasma, amniotic fluid, and placenta following AVP infusion. Conversely, the T2-associated anti-inflammatory cytokine IL-4 was decreased in the maternal and fetal kidneys from AVP-infused dams, while IL-10 was decreased in the maternal kidney and all fetal tissues. Collectively, these results demonstrate the sufficiency of AVP to induce the immune changes typical of PreE. We investigated if T cells can respond directly to AVP by evaluating the expression of AVP receptors (AVPRs) on mouse and human CD4+ T cells. Mouse and human T cells expressed AVPR1a, AVPR1b, and AVPR2. The expression of AVPR1a was decreased in CD4+ T cells obtained from PreE-affected women. In total, our data are consistent with a potential initiating role for AVP in the immune dysfunction typical of PreE and identifies putative signaling mechanism(s) for future investigation.

Intravenous immune globulin (IVIG), a polyvalent solution of pooled human immunoglobulin, is a potent immunomodulating agent. It is currently approved to treat autoimmune diseases, including idiopathic thrombocytopenia purpura, autoimmune hemolytic anemia, and Kawasaki disease. The basis of IVIG's immunomodulatory properties is not entirely understood. Proposed mechanisms include Fc receptor blockade, interference with cytokine network, and provision of anti-idiotypic antibodies. IVIG has also been shown to affect T-lymphocyte function, although a direct effect has been difficult to reconcile given the lack of immunoglobulin or Fc-receptors on T cells. Experiments were thus carried out to determine whether IVIG was acting on a specific T-cell subset and at the level of the T-cell receptor (TCR), and whether cytokine expression patterns were modulated. T lymphocytes obtained from adult peripheral blood and umbilical cord blood were cultured over a 1-wk time course in the presence of pharmacological IVIG concentrations (Gamunex(®) , 0-2.0 mg/ml). Cells were exposed to various stimulation conditions, and TCR signaling competence was assessed by quantifying activation-induced upregulation of CD25 and CD69, as well as production of specific T-cell cytokines. IVIG was found to significantly decrease T-lymphocyte proliferation, in a dose and time-dependent manner, in both cord and adult blood. IVIG markedly reduced phytohemagglutinin and anti-CD3-induced upregulation of CD25 and CD69 in both CD4 and CD8 T-cell subsets, although phorbol ester-induced responses were intact, suggesting a defect in the CD3/TCR signaling pathway. IVIG also inhibited anti-CD3-induced cytokine production of IL-10, IL-2, and IFN-γ in a dose-dependent manner. These data suggest that IVIG may have direct T-cell immunomodulatory properties by dampening TCR responses. Further studies are needed to more precisely define the molecular targets of IVIG.

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