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Am J Epidemiol 2002; 156:882.
Copyright © 2002 by Johns
Hopkins Bloomberg School of Public Health
LETTERS TO THE EDITOR |
RE: "DOES THE SIBLING EFFECT HAVE ITS ORIGIN IN UTERO? INVESTIGATING BIRTH ORDER, CORD BLOOD IMMUNOGLOBULIN E CONCENTRATION, AND ALLERGIC SENSITIZATION AT AGE 4 YEARS"
Institute of Epidemiology and Social Medicine Domagkstrasse 3 Muenster 48129, Germany
I read with interest the article by Karmaus et al. that was published recently in the American Journal of Epidemiology (1). Their finding that sibship size can influence allergic phenotype in children via prebirth factors is intriguing and actually can help explain earlier results which show that asthma is inversely related to the presence of older siblings, while early respiratory infections increase rather than decrease the risk of developing asthma (2). Karmaus et al. suggest that intrauterine factors can program the pattern of T helper 2 (Th2) and T helper 1 (Th1) cell response, with increased cord blood immunoglobulin E being a marker, and subsequently the number of infections and the risk of atopy (1). Thus, according to Karmaus et al., the negative association between infection and atopic manifestation is not causal but is more likely to be spurious (1).
My problem with such an interpretation is that it is counterintuitive. According to the Th1-Th2 model, Th1 and Th2 cytokine profiles have cross-regulating abilities; that is, interferon-
can down-regulate Th2 responses, and interleukin-4 can down-regulate Th1 responses (3). For example, if we take a newborn with a Th2-Th1 pattern that is biased at birth towards Th2 responses, with increased cord immunoglobulin E as one of its early manifestations, this child will theoretically be more prone to allergy and to infection (his Th2 cytokines will suppress his Th1 responses to infection), and subsequently Karmaus et al.’s interpretation cannot provide an underlying mechanism by which one can explain both the effect of birth order on allergy and the negative association between infection and atopic manifestation.
REFERENCES
- Karmaus W, Arshad H, Mattes J. Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years. Am J Epidemiol 2001;154:909–15.
[Abstract/Free Full Text] - Nafstad P, Magnus P, Jaakkola JJ. Early respiratory infections and childhood asthma. Pediatrics 2000;106:E38.[Web of Science][Medline]
- Wills-Karp M. Immunological basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 1999;17:225–81.
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  W. Karmaus, H. Arshad, and J. Mattes THE AUTHORS REPLY Am. J. Epidemiol., November 1, 2002; 156(9): 883 - 884. [Full Text] [PDF]
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