Infant Immune Study (IIS)

Trial Status: 
Current Trial - Enrollment Complete


The Infant Immune Study (IIS) was started in 1996 with the goal of exploring immune system markers of the early life origins of asthma. Over the next 7 years, 482 mothers in the third trimester of pregnancy agreed to enroll their infant in the study at birth. The IIS is a population-based, non-selected, prospective birth cohort study.

The IIS was continuously funded by the National Institutes of Health through 2013. Starting with the prenatal maternal visit, samples and questionnaires have been collected from the mothers, fathers and enrolled children at regular intervals. Including the collection of umbilical cord blood, there have been 7 evaluations completed at ages 3 months, 1, 2, 3, 5, and 9 years of age. At each evaluation, a blood sample was collected and peripheral blood mononuclear cells isolated. A portion of the cells were frozen (fresh frozen) and a portion were cultured and stimulated with mitogens, allergens, respiratory syncytial virus, and lipopolysaccharide. The culture supernatants were then collected and stored for measurement of biomarkers. We have completed measurements of many biomarkers including IFN-y, IL-4, IL-5, IL-10, IL-12, IL-13, and TNF-a. In addition to the blood sample drawn for cell cultures, additional blood samples were drawn for serum/plasma, DNA extraction and complete blood cell counts. Serum/plasma levels of total IgE and allergen-specific IgE to several aeroallergens and foods have been completed. At age 9 years, children performed pulmonary function testing (PFT) and bronchial hyper-responsiveness testing (cold air challenge). Allergy skin prick tests to local aeroallergens were performed on the children at ages 5 and 9 years and on the parents when the children were 5 years old.

Two of the strengths of the IIS study are the longitudinal biomarker measurements and the detailed data available for illnesses and infant feeding practices during the first year of life. Of the 482 IIS participants, 430 have childhood respiratory health data between the ages 2 and 9 years. Similar to CRS, our main measure of asthma is derived from the questionnaires and is defined as a physician diagnosis of asthma with episodes or attacks of asthma and/or wheeze during the previous year. Childhood asthma is present for 18% (n=77) of the IIS participants.

Research Specialties: 





PubMed Citations: 

Oddy WH, Halonen M, Martinez FD, Lohman IC, Stern DA, Kurzius-Spencer M, et al. TGF-beta in human milk is associated with wheeze in infancy. The Journal of allergy and clinical immunology. 2003;112(4):723-8. Epub 2003/10/18. doi: 10.1016/S0091. PubMed PMID: 14564350


Guerra S, Carla Lohman I, LeVan TD, Wright AL, Martinez FD, Halonen M. The differential effect of genetic variation on soluble CD14 levels in human plasma and milk. Am J Reprod Immunol. 2004;52(3):204-11. Epub 2004/09/18. doi: 10.1111/j.1600-0897.2004.00207.x. PubMed PMID: 15373760


Guerra S, Lohman IC, Halonen M, Martinez FD, Wright AL. Reduced interferon gamma production and soluble CD14 levels in early life predict recurrent wheezing by 1 year of age. American journal of respiratory and critical care medicine. 2004;169(1):70-6. Epub 2003/10/04. doi: 10.1164/rccm.200304-499OC. PubMed PMID: 14525803


Kurzius-Spencer M, Halonen M, Carla Lohman I, Martinez FD, Wright AL. Prenatal factors associated with the development of eczema in the first year of life. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2005;16(1):19-26. Epub 2005/02/08. doi: 10.1111/j.1399-3038.2005.00233.x. PubMed PMID: 15693907

LeVan TD, Guerra S, Klimecki W, Vasquez MM, Lohman IC, Martinez FD, et al. The impact of CD14 polymorphisms on the development of soluble CD14 levels during infancy. Genes and immunity. 2006;7(1):77-80. Epub 2006/01/06. doi: 10.1038/sj.gene.6364276. 


Crestani E, Lohman IC, Guerra S, Wright AL, Halonen M. Association of IL-5 cytokine production and in vivo IgE levels in infants and parents. The Journal of allergy and clinical immunology. 2007;120(4):820-6. Epub 2007/07/14. doi: 10.1016/j.jaci.2007.05.033. PubMed PMID: 17628648


Rothers J, Stern DA, Spangenberg A, Lohman IC, Halonen M, Wright AL. Influence of early day-care exposure on total IgE levels through age 3 years. The Journal of allergy and clinical immunology. 2007;120(5):1201-7. Epub 2007/09/15. doi: 10.1016/j.jaci.2007.07.036. PubMed PMID: 17854882


Halonen M, Lohman IC, Stern DA, Spangenberg A, Anderson D, Mobley S, et al. Th1/Th2 patterns and balance in cytokine production in the parents and infants of a large birth cohort. J Immunol. 2009;182(5):3285-93. Epub 2009/02/24. doi: 10.4049/jimmunol.0711996. PubMed PMID: 19234227


Bosco A, Ehteshami S, Stern DA, Martinez FD. Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction. Mucosal immunology. 2010;3(4):399-409. Epub 2010/03/26. doi: 10.1038/mi.2010.13. PubMed PMID: 20336062


Maier RM, Palmer MW, Andersen GL, Halonen MJ, Josephson KC, Maier RS, et al. Environmental determinants of and impact on childhood asthma by the bacterial community in household dust. Applied and environmental microbiology. 2010;76(8):2663-7. Epub 2010/02/16. doi: 10.1128/AEM.01665-09. PubMed PMID: 20154107


Su Y, Rothers J, Stern DA, Halonen M, Wright AL. Relation of early antibiotic use to childhood asthma: confounding by indication? Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2010;40(8):1222-9. Epub 2010/06/16. doi: 10.1111/j.1365-2222.2010.03539.x. PubMed PMID: 20545705


Custovic A, Rothers J, Stern D, Simpson A, Woodcock A, Wright AL, et al. Effect of day care attendance on sensitization and atopic wheezing differs by Toll-like receptor 2 genotype in 2 population-based birth cohort studies. The Journal of allergy and clinical immunology. 2011;127(2):390-7 e1-9. Epub 2011/02/02. doi: 10.1016/j.jaci.2010.10.050. 


Rothers J, Halonen M, Stern DA, Lohman IC, Mobley S, Spangenberg A, et al. Adaptive cytokine production in early life differentially predicts total IgE levels and asthma through age 5 years. The Journal of allergy and clinical immunology. 2011;128(2):397-402 e2. Epub 2011/06/21. doi: 10.1016/j.jaci.2011.04.044. PubMed PMID: 21683432

Rothers, Stern, Lohman 1, Amber Spangenberg 1, Anne L Wright 1 3, Avery DeVries 1 4, Donata Vercelli 1 4, Marilyn Halonen 

Rothers J, Wright AL, Stern DA, Halonen M, Camargo CA, Jr. Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona. The Journal of allergy and clinical immunology. 2011;128(5):1093-9 e1-5. Epub 2011/08/23. doi: 10.1016/j.jaci.2011.07.015. PubMed PMID: 21855975


Sevgican U, Rothers J, Stern DA, Lohman IC, Wright AL. Predictors of neonatal production of IFN-gamma and relation to later wheeze. The Journal of allergy and clinical immunology. 2012;129(2):567-8, 8 e1. Epub 2011/11/01. doi: 10.1016/j.jaci.2011.09.032. PubMed PMID: 22036249


Halonen M, Lohman IC, Stern DA, Ellis WL, Rothers J, Wright AL. Perinatal tumor necrosis factor-alpha production, influenced by maternal pregnancy weight gain, predicts childhood asthma. American journal of respiratory and critical care medicine. 2013;188(1):35-41. Epub 2013/04/18. doi: 10.1164/rccm.201207-1265OC. PubMed PMID: 23590270


Thompson EE, Myers RA, Du G, Aydelotte TM, Tisler CJ, Stern DA, et al. Maternal microchimerism protects against the development of asthma. The Journal of allergy and clinical immunology. 2013;132(1):39-44. Epub 2013/02/26. doi: 10.1016/j.jaci.2012.12.1575. PubMed PMID: 23434286


Oren E, Rothers J, Stern DA, Morgan WJ, Halonen M, Wright AL. Cough during infancy and subsequent childhood asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2015;45(9):1439-46. Epub 2015/05/27. doi: 10.1111/cea.12573. PubMed PMID: 26011047


Janet Rothers, Debra A Stern, Carla Lohman, Amber Spangenberg , Anne L Wright, Avery DeVries, Donata Vercelli, Marilyn Halonen. Maternal Cytokine Profiles during Pregnancy Predict Asthma in Children of Mothers without Asthma. Am J Respir Cell Mol Biol. 2018 Nov;59(5):592-600. doi: 10.1165/rcmb.2017 0410OC.PMID: 29863910

Research Area: 
Applied and Basic Research
Disease Type: 
Allergy, Asthma, Genetics, Immunology

Pub Med Citations (using Bliblio)

DeVries A, McCauley K, Fadrosh D, et al. "Maternal prenatal immunity, neonatal trained immunity, and early airway microbiota shape childhood asthma development." Allergy. 2022;77(12):3617-3628. PMCID: PMC9712226  PMID: 35841380

Mosley EE, Wright AL, McGuire MK, McGuire MA. "trans Fatty acids in milk produced by women in the United States." Am J Clin Nutr. 2005;82(6):1292-7. PMID: 16332663