| Allergy, Asthma & Clinical Immunology | |
| Maternal immune markers in serum during gestation and in breast milk and the risk of asthma-like symptoms at ages 6 and 12 months: a longitudinal study | |
| Nelís Soto-Ramírez1  Wilfried Karmaus1  Mitra Yousefi1  Hongmei Zhang1  Jihong Liu1  Venugopal Gangur2  | |
| [1] Epidemiology and Biostatistics Department, Norman J Arnold School of Public Health, University of South Carolina, 800 Sumter Street, Columbia, SC, 29208, USA | |
| [2] Food Allergy and Immunology, Department of Food Science and Human Nutrition, Michigan State University, 302B G.M. Trout FSHN Building, East Lansing, MI, 48824-1224, USA | |
| 关键词: Longitudinal study; Children; Asthma-like symptoms; Chemokines; Cytokines; Immune markers; Maternal serum; Breast milk; | |
| Others : 792450 DOI : 10.1186/1710-1492-8-11 |
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| received in 2012-01-06, accepted in 2012-06-05, 发布年份 2012 | |
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【 摘 要 】
Background
The role of breast milk on the risk of childhood asthma is in dispute. The aim of this prospective study is to determine the relationship of immune markers in maternal serum during gestation and breast milk to asthma-like symptoms (AS) in infancy.
Methods
Pregnant women were recruited in Columbia and Charleston, South Carolina. Blood (median: three weeks before delivery) and breast milk (three weeks after delivery) samples were collected. Concentrations of interferon (IFN)-γ, IFN gamma-induced protein 10 (IP-10 or CXCL10), CCL11, interleukin (IL) 1β, IL-4, IL-5, IL-6, CXCL8, IL-10, IL-12(p70), IL-13, transforming growth factor (TGF)-β1, and immunoglobulin (Ig) A in both maternal serum and milk whey were determined via immunoassays. Asthma-like symptoms (AS) of the infant were ascertained at 6 and 12 months, respectively. Generalized estimating equations assessed relative risks (RRs) of immune markers for repeated measurements of AS, considering intra-individual correlations and adjusting for confounders. To provide comparable risk estimates, quartiles of the immune markers were used, except for IL-5 in whey and IgA in serum, which were dichotomized.
Results
Of 178 women, 161 provided blood and 115 breast milk samples. IL-12(p70), IL-4, IL-10, IL-1β, and CCL11 in serum and in whey were not further considered for the statistical analyses since the proportion of non-detectable values was high. Most immune markers in serum and milk whey were moderately or highly correlated; however, IgA was negatively correlated. Infants in the highest quartile of IL-13 in both serum and whey were at a higher risk of AS (RR = 3.02 and 4.18; respectively) compared to infants in the first quartile. High levels of IL-5 in serum and whey was also identified as a risk. In addition, increased secretory IgA and TGF-β1 in breast milk reduced the risks of AS.
Conclusions
Maternal serum and whey levels of IL-5 and IL-13 are risk markers for AS; whey IgA and TGF-β1 seem to be protective. Only focusing on breast milk portend that milk cytokines IL-5 and IL-13 have adverse effects. However, similar immune exposures during late gestation and via milk suggest that both may enhance AS among infants.
【 授权许可】
2012 Soto-Ramirez et al.; licensee BioMed Central Ltd.
【 预 览 】
| Files | Size | Format | View |
|---|---|---|---|
| 20140705031456135.pdf | 332KB | ||
| Figure 1. | 34KB | Image |
【 图 表 】
Figure 1.
【 参考文献 】
- [1]Eigenmann PA, Antonella Muraro M, Sampson HA, Wahn U: iPAC: an initiative to fight the burden of allergies in children. Pediatr Allergy Immunol 2008, 19(Suppl 19):1-3.
- [2]Bloom BCR, Freeman G: Summary Health Statistics for U.S. Children: National Health Interview Survey. 2009. http://www.cdc.gov/nchs/data/series/sr_10/sr10_244.pdf webcite
- [3]Department of Health and Human Services: Action against asthma: A strategic plan for the Department of Health and Human Services. http://aspe.hhs.gov/sp/asthma/ webcite
- [4]Cushing AH, Samet JM, Lambert WE, Skipper BJ, Hunt WC, Young SA, McLaren LC: Breastfeeding reduces risk of respiratory illness in infants. Am J Epidemiol 1998, 147:863-870.
- [5]Oddy WH: Breastfeeding protects against illness and infection in infants and children: a review of the evidence. Breastfeed Rev 2001, 9:11-18.
- [6]Kull I, Melen E, Alm J, Hallberg J, Svartengren M, van Hage M, Pershagen G, Wickman M, Bergstrom A: Breast-feeding in relation to asthma, lung function, and sensitization in young school children. J Allergy Clin Immunol 2010, 125:1013-9.
- [7]Kull I, Almqvist C, Lilja G, Pershagen G, Wickman M: Breast-feeding reduces the risk of asthma during the first 4 years of life. J Allergy Clin Immunol 2004, 114:755-760.
- [8]Giwercman C, Halkjaer LB, Jensen SM, Bonnelykke K, Lauritzen L, Bisgaard H: Increased risk of eczema but reduced risk of early wheezy disorder from exclusive breast-feeding in high-risk infants. J Allergy Clin Immunol 2010, 125:866-871.
- [9]Midodzi WK, Rowe BH, Majaesic CM, Saunders LD, Senthilselvan A: Early life factors associated with incidence of physician-diagnosed asthma in preschool children: results from the Canadian Early Childhood Development cohort study. J Asthma 2010, 47:7-13.
- [10]Chulada PC, Arbes SJ Jr, Dunson D, Zeldin DC: Breast-feeding and the prevalence of asthma and wheeze in children: analyses from the Third National Health and Nutrition Examination Survey, 1988–1994. J Allergy Clin Immunol 2003, 111:328-336.
- [11]Oddy WH, Holt PG, Sly PD, Read AW, Landau LI, Stanley FJ, Kendall GE, Burton PR: Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ 1999, 319:815-819.
- [12]Gdalevich M, Mimouni D, Mimouni M: Breast-feeding and the risk of bronchial asthma in childhood: a systematic review with meta-analysis of prospective studies. J Pediatr 2001, 139:261-266.
- [13]Bener A, Ehlayel MS, Alsowaidi S, Sabbah A: Role of breast feeding in primary prevention of asthma and allergic diseases in a traditional society. Eur Ann Allergy Clin Immunol 2007, 39:337-343.
- [14]der Voort AM S-, Jaddoe VV, van der Valk RJ, Willemsen SP, Hofman A, Moll HA, de Jongste JC, Duijts L: Duration and exclusiveness of breastfeeding and childhood asthma-related symptoms. Eur Respir J 2012, 39:81-9.
- [15]Wright AL, Holberg CJ, Taussig LM, Martinez FD: Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood. Thorax 2001, 56:192-197.
- [16]Sears MR, Greene JM, Willan AR, Taylor DR, Flannery EM, Cowan JO, Herbison GP, Poulton R: Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002, 360:901-907.
- [17]Burgess SW, Dakin CJ, O'Callaghan MJ: Breastfeeding does not increase the risk of asthma at 14 years. Pediatrics 2006, 117:e787-792.
- [18]Kramer MS, Matush L, Vanilovich I, Platt R, Bogdanovich N, Sevkovskaya Z, Dzikovich I, Shishko G, Mazer B: Effect of prolonged and exclusive breast feeding on risk of allergy and asthma: cluster randomised trial. BMJ 2007, 335:815.
- [19]Rust GS, Thompson CJ, Minor P, Davis-Mitchell W, Holloway K, Murray V: Does breastfeeding protect children from asthma? Analysis of NHANES III survey data. J Natl Med Assoc 2001, 93:139-148.
- [20]Zhu J, Paul WE: Heterogeneity and plasticity of T helper cells. Cell Res 2010, 20:4-12.
- [21]Romagnani S: Th1/Th2 cells. Inflamm Bowel Dis 1999, 5:285-294.
- [22]Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, Fear D, Smurthwaite L: The biology of IgE and the basis of allergic disease. Annu Rev Immunol 2003, 21:579-628.
- [23]Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, Mitchell EA, Pearce N, Sibbald B, Stewart AW: International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J 1995, 8:483-491.
- [24]R&D Systemshttp://www.rndsystems.com/pdf/DB100B.pdf webcite
- [25]Bio-Radhttp://www.bio-rad.com/webroot/web/pdf/lsr/literature/10014905.pdf webcite
- [26]Immunology Consultants Laboratory, Inc http://www.icllab.com/commerce/ccp2469-human-iga-elisa-kit-e-80a.htm webcite
- [27]Wolfinger R, Chang M: Comparing the SAS GLM and MIXED Procedures for Reated Measures. http://www.ats.ucla.edu/stat/sas/library/mixedglm.pdf webcite
- [28]Næs T, Mevik BH: Understanding the collinearity problem in regression and discriminant analysis. J Chemom 2001, 15:413-426.
- [29]Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc Ser B Meth 1995, 57:289-300.
- [30]Databook SCPRAMS: Surveillance Report on Maternal Health and Experiences during Pregnancy and the Early Infancy Period. In Office of Public Health Statistics and Information Services. Department of Health and Environmental Control, Columbia, South Carolina, USA, South Carolina; 2010.
- [31]Garofalo R, Chheda S, Mei F, Palkowetz KH, Rudloff HE, Schmalstieg FC, Rassin DK, Goldman AS: Interleukin-10 in human milk. Pediatr Res 1995, 37:444-449.
- [32]Yilmaz HL, Saygili-Yilmaz ES, Gunesacar R: Interleukin-10 and −12 in human milk at 3 stages of lactation: a longitudinal study. Adv Ther 2007, 24:603-610.
- [33]Bryan DL, Hawkes JS, Gibson RA: Interleukin-12 in human milk. Pediatr Res 1999, 45:858-859.
- [34]Bottcher MF, Jenmalm MC, Bjorksten B, Garofalo RP: Chemoattractant factors in breast milk from allergic and nonallergic mothers. Pediatr Res 2000, 47:592-597.
- [35]Agarwal SKW, Davis S, Gangur V: Immune Markers in Breast Milk and Fetal and Maternal Body Fluids: A Systematic Review of Perinatal Concentrations. J Hum Lact 2011, 27:171-186.
- [36]Ober C, Yao TC: The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev 2011, 242:10-30.
- [37]Matheson MC, Allen KJ, Tang ML: Understanding the evidence for and against the role of breastfeeding in allergy prevention. Clin Exp Allergy 2012. Epub ahead of print
- [38]Martinez FD, Helms PJ: Types of asthma and wheezing. Eur Respir J Suppl 1998, 27:3s-8s.
- [39]Silvestri M, Sabatini F, Defilippi AC, Rossi GA: The wheezy infant -- immunological and molecular considerations. Paediatr Respir Rev 2004, 5(Suppl A):S81-87.
- [40]Kropf J, Schurek JO, Wollner A, Gressner AM: Immunological measurement of transforming growth factor-beta 1 (TGF-beta1) in blood; assay development and comparison. Clin Chem 1997, 43:1965-1974.
- [41]Barnes PJ: The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 2008, 118:3546-3556.
- [42]Vercelli D, Jabara HH, Arai K, Geha RS: Induction of human IgE synthesis requires interleukin 4 and T/B cell interactions involving the T cell receptor/CD3 complex and MHC class II antigens. J Exp Med 1989, 169:1295-1307.
- [43]Del Prete G, Maggi E, Parronchi P, Chretien I, Tiri A, Macchia D, Ricci M, Banchereau J, De Vries J, Romagnani S: IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J Immunol 1988, 140:4193-4198.
- [44]Gascan H, Gauchat JF, Roncarolo MG, Yssel H, Spits H, de Vries JE: Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones. J Exp Med 1991, 173:747-750.
- [45]Takatsu K, Nakajima H: IL-5 and eosinophilia. Curr Opin Immunol 2008, 20:288-294.
- [46]Bottcher MF, Fredriksson J, Hellquist A, Jenmalm MC: Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production. Pediatr Allergy Immunol 2003, 14:27-34.
- [47]Bottcher MF, Haggstrom P, Bjorksten B, Jenmalm MC: Total and allergen-specific immunoglobulin A levels in saliva in relation to the development of allergy in infants up to 2 years of age. Clin Exp Allergy 2002, 32:1293-1298.
- [48]Bottcher MF, Jenmalm MC: Breastfeeding and the development of atopic disease during childhood. Clin Exp Allergy 2002, 32:159-161.
- [49]Bottcher MF, Jenmalm MC, Bjorksten B: Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants. Pediatr Allergy Immunol 2003, 14:35-41.
- [50]Savilahti E, Siltanen M, Kajosaari M, Vaarala O, Saarinen KM: IgA antibodies, TGF-beta1 and -beta2, and soluble CD14 in the colostrum and development of atopy by age 4. Pediatr Res 2005, 58:1300-1305.
- [51]Saarinen KM, Vaarala O, Klemetti P, Savilahti E: Transforming growth factor-beta1 in mothers' colostrum and immune responses to cows' milk proteins in infants with cows' milk allergy. J Allergy Clin Immunol 1999, 104:1093-1098.
- [52]Hanson L, Silfverdal SA, Stromback L, Erling V, Zaman S, Olcen P, Telemo E: The immunological role of breast feeding. Pediatr Allergy Immunol 2001, 12:15-19.
- [53]Hanson LA: Breastfeeding provides passive and likely long-lasting active immunity. Ann Allergy Asthma Immunol 1998, 81:523-533.
- [54]Oddy WH, Halonen M, Martinez FD, Lohman IC, Stern DA, Kurzius-Spencer M, Guerra S, Wright AL: TGF-beta in human milk is associated with wheeze in infancy. J Allergy Clin Immunol 2003, 112:723-728.
- [55]Yoo EM, Morrison SL: IgA: an immune glycoprotein. Clin Immunol 2005, 116:3-10.
- [56]Mestecky J, Russell MW: IgA subclasses. Monogr Allergy 1986, 19:277-301.
- [57]Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P: The immune geography of IgA induction and function. Mucosal Immunol 2008, 1:11-22.
- [58]Weemaes C, Klasen I, Goertz J, Beldhuis-Valkis M, Olafsson O, Haraldsson A: Development of immunoglobulin A in infancy and childhood. Scand J Immunol 2003, 58:642-648.
- [59]Brandtzaeg P, Nilssen DE, Rognum TO, Thrane PS: Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol Clin North Am 1991, 20:397-439.
- [60]Pesonen M, Kallio MJ, Siimes MA, Savilahti E, Ranki A: Serum immunoglobulin A concentration in infancy, but not human milk immunoglobulin A, is associated with subsequent atopic manifestations in children and adolescents: a 20-year prospective follow-up study. Clin Exp Allergy 2011, 41:688-696.
- [61]Prescott SL, Taylor A, Roper J, Wahdan A, Noakes P, Thornton C, Dunstan J, Upham JW: Maternal reactivity to fetal alloantigens is related to newborn immune responses and subsequent allergic disease. Clin Exp Allergy 2005, 35:417-425.
- [62]Prescott SL: Allergic disease: understanding how in utero events set the scene. Proc Nutr Soc 2010, 69:366-372.
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