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Biomedical subjects

Elizabeth Anderson

Publications and source records attributed to Elizabeth Anderson.

At least 19 recordsLinked to original sources
PubMed2022

A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.

Animals↗
PubMed2006

Sex-related differences in immune development and the expression of atopy in early childhood.

BACKGROUND: Sex and age are known to influence the clinical expression of asthma and allergic diseases. OBJECTIVE: We sought to evaluate whether immune response profiles also vary by sex and age. METHODS: We performed a prospective birth cohort study (Childhood Origins of Asthma) designed to evaluate interactions among age, sex, immune responses, and virus infections on the development of asthma and allergic diseases. Two hundred eighty-nine subjects were enrolled at birth, and 275 maintained prospective follow-up for 3 years. Cytokine response profiles at birth, 1, and 3 years of age; rates of wheezing, atopic dermatitis, and viral illnesses; and biomarkers of atopy, including total and specific IgE levels and peripheral eosinophil counts, were evaluated. RESULTS: PHA-induced IFN-gamma responses were higher in boys at 1 year of age (median, 35 vs 19 pg/mL; P < .001) and at 3 years of age (median, 282 vs 181 pg/mL; P = .07). Among children who wheezed during the third year of life, boys had increased IFN-gamma, IL-5, and IL-13 responses at age 3 years (P < .001, P = .008, and P = .01, respectively). Boys also demonstrated increased rates of sensitization (P = .05 at year 1), total IgE levels (P = .03 at year 1 and P = .006 at year 3), and peripheral eosinophil counts (2.62 vs 1.85; P = .05 at year 3). CONCLUSION: Sex-specific differences in immune responses develop during early childhood; some of these differences developmentally proceed, whereas others occur in parallel to the clinical expression of various atopic phenotypes. CLINICAL IMPLICATIONS: The differential expression of atopic diseases between boys and girls in early childhood is accompanied by sex-specific differences in immune response profiles.

Cells, Cultured↗
PubMed2006

Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo.

INTRODUCTION: The ras pathway is essential for cell growth and proliferation. The effects of R115777, a farnesyl transferase inhibitor, were investigated in cancer cell lines expressing varying levels of growth factor receptors and with differing ras status. Effects on tumour xenografts and human ductal carcinoma in situ (DCIS) of the breast in a xenograft mouse model were also tested. METHOD: In vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3 and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments, cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to form tumours. Proliferation and apoptosis were determined by immunohistochemistry in xenografts and cell tumours. RESULTS: The 50% inhibitory concentrations varied a hundred-fold, from 39 nmol/l (+/- 26 nmol/l) for SKBR3 to 5.9 micromol/l(+/- 0.8 micromol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of tumour growth inhibition were approximately 85% and 40%, respectively. There was a significant decrease in the cell turnover index (CTI; proliferation/apoptosis). In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS xenografts proliferation decreased and apoptosis increased. The CTI ratio between the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts. CONCLUSION: Treatment with the farnesyl transferase inhibitor reduced cell growth in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced CTI. R115777 is a promising treatment for breast cancer but the relation between effect and growth factor receptor and ras status has to be established.

Animals↗
PubMed2006

Treatment advice in primary care: a comparative study of nurse practitioners and general practitioners.

AIM: This paper reports a study comparing the content of talk about treatments by nurse practitioners and general practitioners in order to understand how this might be related to satisfaction. BACKGROUND: Studies show that satisfaction with nurse practitioner care is high when compared with that given by general practitioners. Clinical outcomes are similar. Nurse practitioners spend statistically significantly longer on consultations, and spend more time discussing treatments as well as social and emotional aspects of patients' lives. METHODS: Based on transcripts of audiotaped consultations, clinicians' talk about treatment was compared across 18 matched pairs of nurse practitioner and general practitioner consultations where 'same day' appointments were sought. Case studies of six paired consultations were analysed in depth. The data were collected in 1998 in the United Kingdom. RESULTS: A statistically significantly greater proportion of nurse practitioners' talk concerned treatments, with talk about how to use treatments and discussion of side effects contributing most to the difference. Nurse practitioners also recommended a greater number of treatments. Qualitative comparison of case study pairs suggested that nurse practitioners demonstrated greater concern with the acceptability and cost of treatments to patients. CONCLUSIONS: Nurses offered more holistic care to these patients and it is likely that this, and the greater provision of information, led to the higher levels of satisfaction found by other investigators. General practitioners are more focused on gathering information directly relevant to diagnosing and treating the immediate presenting complaint. Both types of practitioner may benefit from seeing the detailed illustrations of different approaches provided.

England↗
PubMed2006

'Taking off the suit': engaging the community in primary health care decision-making.

OBJECTIVE: To explore the process of public involvement in planning primary health care. BACKGROUND: Recent policy in the UK promotes public involvement in planning health but there have been difficulties in engaging communities in the process. Surveys of health service organizations have found that there has been a failure to adapt to new approaches. It has become important to understand why this has occurred if policy initiatives to encourage involvement are to succeed. DESIGN: Qualitative study. Data collected through individual interviews and focus groups. SETTING: Two new primary healthcare developments in deprived areas in Bristol and Weston-Super-Mare. PARTICIPANTS: Thirty-six professionals and 23 local residents in Bristol; six professionals and three local residents in Weston-Super-Mare. RESULTS: Three themes were identified: process, partnership and power. The main findings were that exceptional people with a shared commitment to public involvement were necessary to motivate others and develop partnerships. Local people were drawn into the process and with increased confidence became powerful advocates for their community. Creative and varied methods to involve the public were important in achieving balance between professionals and lay people. However, conflicts over practical decisions arose from a lack of clarity over who had power to influence decisions. CONCLUSION: Most of the participants were enthusiastic about their experience of public involvement in planning primary health care. Features crucial to sustainable involvement included a commitment from leaders within statutory agencies, support over a long period to build the confidence of local people, willingness to use informal approaches that are in tune with local culture, and a recognition of the concerns of both service users and providers.

Adult↗
PubMed2006

Cooperative action of tamoxifen and c-Src inhibition in preventing the growth of estrogen receptor-positive human breast cancer cells.

It has long been appreciated that estrogenic signaling contributes to breast cancer progression. c-Src is also required for a number of processes involved in tumor progression and metastasis. We have previously identified the K303R mutant estrogen receptor alpha (ERalpha) that confers hypersensitivity to low levels of estrogen. Because ERalpha and c-Src have been shown to interact in a number of different systems, we wanted to evaluate the role of c-Src kinase in estrogen-stimulated growth and survival of ERalpha-positive breast cancer cells. MCF-7 cells stably expressing the mutant receptor showed increased c-Src kinase activity and c-Src tyrosine phosphorylation when compared with wild-type ERalpha-expressing cells. A c-Src inhibitor, AZD0530, was used to analyze the biological effects of pharmacologically inhibiting c-Src kinase activity. MCF-7 cells showed an anchorage-dependent growth IC50 of 0.47 micromol/L, which was increased 4-fold in the presence of estrogen. In contrast, cells stably expressing the mutant ERalpha had an elevated IC50 that was only increased 1.4-fold by estrogen stimulation. The c-Src inhibitor effectively inhibited the anchorage-independent growth of both of these cells, and estrogen was able to reverse these effects. When cells were treated with suboptimal concentrations of c-Src inhibitor and tamoxifen, synergistic inhibition was observed, suggesting a cooperative interaction between c-Src and ERalpha. These data clearly show an important role for ERalpha and estrogen signaling in c-Src-mediated breast cancer cell growth and survival. Here, we show that c-Src inhibition is blocked by estrogen signaling; thus, the therapeutic use of c-Src inhibitors may require inhibition of ERalpha in estrogen-dependent breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

A phase I study of dose-dense topotecan given upfront to standard therapy in patients with small cell lung cancer.

OBJECTIVE: To determine the feasibility and maximum tolerated dose of dose-dense topotecan as induction chemotherapy before standard therapy (carboplatin plus etoposide alone or in combination with radiotherapy) in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with SCLC and good performance status were eligible. Three 2-week cycles of dose-dense topotecan administered on days 1-3 with granulocyte colony-stimulating factor support were followed by four cycles of standard carboplatin plus etoposide therapy alone (extensive-stage SCLC) or with radiotherapy (limited-stage SCLC). The dose of topotecan was escalated from 1.5 mg/m2/day to 2.5 mg/m2/day in increments of 0.25 mg/m2/day within cohorts of 3-5 patients each. Dose-limiting toxicity was defined as any grade 3 or 4 toxicity resulting in a treatment reduction or a delay of >3 days. RESULTS: Twenty-two patients with SCLC (5 limited-stage, 17 extensive-stage) were enrolled. Treatment was well tolerated. The dose-limiting toxicities were thrombocytopenia and neutropenia, and the maximum tolerated dose of dose-dense topotecan induction therapy was 2.25 mg/m2/day. Overall, topotecan-related grade 3/4 haematological toxicities included neutropenia (n = 4), thrombocytopenia (n = 3) and febrile neutropenia (n = 1). No grade 4 non-haematological toxicities occurred. Grade 3 adverse events included nausea (n = 2), renal toxicity (n = 1) and anorexia (n = 1). Toxicity during the carboplatin plus etoposide +/- radiotherapy phase of therapy was consistent with that reported in previous trials. The overall response rate was 80% for limited-stage and 76% for extensive-stage SCLC. Median survival was 8 months in patients with limited-stage SCLC and 13.5 months for patients with extensive-stage SCLC. CONCLUSION: The results of this phase I study suggest that a regimen of sequential dose-dense topotecan and carboplatin plus etoposide is feasible, and the preliminary activity observed in patients with SCLC warrants further investigation at a starting dose of topotecan 2.25 mg/m2/day.

Anorexia↗
PubMed2006

Comparing the cost of nurse practitioners and GPs in primary care: modelling economic data from randomised trials.

BACKGROUND: The role of nurse practitioners in primary care has recently expanded. While there are some outcome data available for different types of consultations, little is known about the relative cost. AIM: To compare the cost of primary care provided by nurse practitioners with that of salaried GPs. DESIGN OF STUDY: Synthesis, modelling, and analysis of published data from the perspective of general practices and the NHS. DATA SOURCES: Two published randomised controlled trials. METHOD: A dataset of resource use for a simulated group of patients in a typical consultation was modelled. Current unit costs were used to obtain a consensus mean cost per consultation. RESULTS: Mean cost of a nurse practitioner consultation was estimated at 9.46 UK pounds (95% confidence interval [CI] = 9.16 to 9.75 pounds) and for a GP was 9.30 UK pounds (95% CI = 9.04 to 9.56 pounds) according to salary and overheads, that is, from the perspective of general practices. From the NHS perspective, which included training costs, the estimated mean costs were 30.35 UK pounds (95% CI = 27.10 to 33.59 pounds) and 28.14 UK pounds (95% CI = 25.43 to 30.84 pounds) respectively. Sensitivity analysis suggested that the time spent by GPs contributing to nurse practitioners' consultations (including return visits) was an important factor in increasing costs associated with nurse practitioners. CONCLUSION: Employing a nurse practitioner in primary care is likely to cost much the same as employing a salaried GP according to currently available data. There is considerable variability of qualifications and experience of nurse practitioners, which suggests that skill-mix decisions should depend on the full range of roles and responsibilities rather than cost.

Family Practice↗
PubMed2005

Fetal death sex ratios: a test of the economic stress hypothesis.

BACKGROUND: The ratio of male to female live births (i.e. the sex ratio) reportedly falls when populations suffer rare and extreme ambient stressors such as the collapse of national economies. This association has been attributed to the death of male fetuses and to reduced conception of males. We assess the validity of the first of these mechanisms by testing the hypothesis that the fetal death sex ratio varies positively over time with the unemployment rate. Using the unemployment rate also allows us to determine if ambient economic stressors less extreme than collapsing national economies affect the fetal death sex ratio. METHODS: We test our hypotheses by applying time-series methods to monthly counts of fetal deaths and the unemployment rate from the state of California beginning January 1989 and ending December 2001. The methods control for trends, seasonal cycles, and other forms of autocorrelation that could induce spurious associations. RESULTS: Results support the fetal death mechanism in that male fetal deaths increased above the values expected from female deaths and from history in months in which the unemployment rate also increased over its expected value. CONCLUSIONS: Our findings suggest that ambient stressors as common as increasing unemployment elevate the risk of fetal death among males. We discuss the social, economic, and health costs borne by parents and communities afflicted with these fetal deaths.

California↗
PubMed2005

Sex ratios in California following the terrorist attacks of September 11, 2001.

BACKGROUND: Natural and man-made disasters as well as declining economies appear to coincide with reduced odds of male live births among humans (i.e. lower secondary sex ratio). This association has been attributed to excess death of males in gestation and to reduced conception of males. We attempt to empirically discriminate between these two attributions by testing the hypotheses that the attacks of September 11, 2001 were followed in California first by higher fetal death sex ratios and later by lower sex ratios among very low weight births and total live births. METHODS: We apply interrupted time-series methods to the fetal death, very low birth weight, and secondary sex ratios. The methods control for trends, seasonal cycles, and other forms of autocorrelation that could induce spurious associations. RESULTS: Findings support the excess death explanation in that the fetal death sex ratio reached its highest level in the 6 year test period in October and November of 2001, while the very low weight birth sex ratio dropped to its lowest level in 14 years in December of 2001. The secondary sex ratio exhibited its second lowest value in 14 years in December of 2001. No support was found for the reduced conception explanation in that the sex ratio did not differ from expected values 9, 10 or 11 months after the attacks. CONCLUSIONS: We infer support for the excess death explanation at the expense of the reduced conception explanation. We also describe the implications of our findings for public health planning.

Algorithms↗
PubMed2005

A putative human breast stem cell population is enriched for steroid receptor-positive cells.

Breast epithelial stem cells are thought to be the primary targets in the etiology of breast cancer. Since breast cancers mostly express estrogen and progesterone receptor (ERalpha and PR), we examined the biology of these ERalpha/PR-positive cells and their relationship to stem cells in normal human breast epithelium. We employed several complementary approaches to identify putative stem cell markers, to characterise an isolated stem cell population and to relate these to cells expressing the steroid receptors ERalpha and PR. Using DNA radiolabelling in human tissue implanted into athymic nude mice, a population of label-retaining cells were shown to be enriched for the putative stem cell markers p21(CIP1) and Msi-1, the human homolog of Drosophila Musashi. Steroid receptor-positive cells were found to co-express these stem cell markers together with cytokeratin 19, another putative stem cell marker in the breast. Human breast epithelial cells with Hoechst dye-effluxing "side population" (SP) properties characteristic of mammary stem cells in mice were demonstrated to be undifferentiated "intermediate" cells by lack of expression of myoepithelial and luminal apical membrane markers. These SP cells were 6-fold enriched for ERalpha-positive cells and expressed several fold higher levels of the ERalpha, p21(CIP1) and Msi1 genes than non-SP cells. In contrast to non-SP cells, SP cells formed branching structures in matrigel which included cells of both luminal and myoepithelial lineages. The data suggest a model where scattered steroid receptor-positive cells are stem cells that self-renew through asymmetric cell division and generate patches of transit amplifying and differentiated cells.

Analysis of Variance↗
PubMed2005

Unblinding of trial participants to their treatment allocation: lessons from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

BACKGROUND: The gold standard clinical trial design is the double-blind, randomized, controlled trial. No standard practice exists for the "unblinding" of trial participants and no legal obligation is placed on investigators to inform participants of their treatment allocation or study results at the end of a trial. Here we document our experiences of unblinding the 2520 Scottish participants in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS: The objectives of the PROSPER unblinding process were to provide all study participants with their study medication status and on-trial cholesterol levels and to respect the rights of participants not to be unblinded. It was considered imperative by the study executive that the blind was maintained until the presentation and publication of the results. Staff therefore remained "blinded" throughout the unblinding process. Inappropriate contact with the PROSPER participants was avoided by confirming their current vital status and health status. RESULTS: To coincide with the presentation of the PROSPER results, all participants, for whom it was deemed appropriate, were sent a summary of the results and were offered the opportunity to be advised of their treatment allocation and on-trial lipid profiles. The majority of participants opted for telephone unblinding. All primary care physicians who had patients randomised to the study were also sent a summary of the study results and sealed documents detailing the treatment allocation and lipid profiles for each patient. Relocated patients were traced and the information forwarded to their new primary care physicians. CONCLUSION: The dissemination of study results and treatment allocation to study participants is an integral part of the research process and should be included in the design of any clinical trial.

Aged↗
PubMed2005

Comparison of GP and nurse practitioner consultations: an observational study.

BACKGROUND: Studies show that satisfaction with nurse practitioner care is high when compared with GPs. Clinical outcomes are similar. Nurse practitioners spend significantly longer on consultations. AIM: We aimed to discover what nurse practitioners do with the extra time, and how their consultations differ from those of GPs. DESIGN OF STUDY: Comparative content analysis of audiotape transcriptions of 18 matched pairs of nurse practitioner and GP consultations. SETTING: Nine general practices in south Wales and south west England. METHOD: Consultations were taped and clinicians' utterances coded into categories developed inductively from the data, and deductively from the literature review. RESULTS: Nurse practitioners spent twice as long with their patients and both patients and clinicians spoke more in nurse consultations. Nurses talked significantly more than GPs about treatments and, within this, talked significantly more about how to apply or carry out treatments. Weaker evidence was found for differences in the direction of nurses being more likely to: discuss social and emotional aspects of patients' lives; discuss the likely course of the patient's condition and side effects of treatments; and to use humour. Some of the extra time was also spent in getting doctors to approve treatment plans and sign prescriptions. CONCLUSIONS: The provision of more information in the longer nurse consultations may explain differences in patient satisfaction found in other studies. Clinicians need to consider how much information it is appropriate to provide to particular patients.

England↗
PubMed2004

Cellular homeostasis and the breast.

Increasing our knowledge regarding the control of cellular homeostasis in the normal human breast is important in understanding how breast tumours arise and whether compounds used for hormone replacement therapy are able to promote tumour formation In our studies on tissue from pre-menopausal, non-pregnant, non-lactating women, oestradiol is the main ovarian steroid mitogen for the breast epithelium whereas progesterone has little or no effect. Oestradiol appears to influence proliferative activity indirectly via oestrogen-receptor positive cells which control the activity of adjacent division competent cells by means of paracrine or juxtacrine growth factors. After the menopause, however, a mitogenic effect of progesterone becomes apparent which may be due to the reduction in endogenous oestradiol levels or, possibly, to tissue specific alterations in steroid sensitivity. Whatever the mechanism, the proliferative effects of progesterone on the post-menopausal breast have implications for the use of HRT.

Breast↗
PubMed2004

Low-dose weekly paclitaxel for recurrent or refractory aggressive non-Hodgkin lymphoma.

BACKGROUND: Many patients with recurrent, intermediate or high-grade non-Hodgkin lymphoma (NHL) may not respond to or are not candidates for aggressive salvage chemotherapy. Effective, less toxic regimens are needed. Although high-dose taxanes have not been reported to be very effective for the treatment of lymphoma, different delivery rates may allow for different mechanisms of action to be manifest and result in a different toxicity profile and response rate. The current study tested this hypothesis by using low-dose, weekly paclitaxel in patients with recurrent or refractory NHL. METHODS: Adults age > 18 years with refractory or recurrent, aggressive NHL who were not considered curable with standard high-dose therapy received paclitaxel at a dose of 80 mg/m2 weekly for 5 weeks for 2 cycles. RESULTS: Thirty-four patients with refractory NHL and 4 patients with recurrent disease were treated. Approximately 45% of the patients had achieved a prior disease remission. The median number of prior regimens received was 3, 74% of the patients had an International Prognostic Index of > or = 3 at the time of study entry, and 29% had failed high-dose therapy with autologous hematopoietic support. Only one patient encountered severe toxicity (sepsis). Myelosuppression was reported to occur in approximately 20% of patients. A total of 10 patients (26%) achieved a complete disease response and 4 patients (11%) achieved a partial response. CONCLUSIONS: In the current study, low-dose, weekly paclitaxel therapy was found to provide a well tolerated and less toxic approach to the treatment of refractory NHL, with encouraging responses noted in heavily pretreated patients. However, evaluation in patients with an earlier stage of disease is warranted.

Adult↗
PubMed2004

Phase 1 trial study of 131I-labeled chimeric 81C6 monoclonal antibody for the treatment of patients with non-Hodgkin lymphoma.

We report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of (131)I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered activity of 1480 MBq (40 mCi), and 2 developed hematologic toxicity that required stem cell infusion. Six patients received an administered activity of 1110 MBq (30 mCi), and 2 developed toxicity that required stem cell infusion. The clearance of whole-body activity was monoexponential with a mean effective half-life of 110 hours (range, 90-136 hours) and a mean effective whole-body residence time of 159 hours (range, 130-196 hours). There was rapid uptake within the viscera; however, tumor uptake was slower. Activity in normal viscera decreased proportional to the whole body; however, tumor sites presented a slow clearance (T(1/2), 86-191 hours). The mean absorbed dose to whole-body was 67 cGy (range, 51-89 hours), whereas the dose to tumor sites was 963 cGy (range, 363-1517 cGy). Despite lack of a "blocking" antibody, 1 of 9 patients attained a complete remission and 1 a partial remission. These data demonstrate this radiopharmaceutical to be an encouraging agent for the treatment of lymphoma particularly if methods to protect the normal viscera are developed.

Animals↗
PubMed2004

Effects of dog ownership and genotype on immune development and atopy in infancy.

BACKGROUND: Exposure to furred pets might confer protection against the development of allergic sensitization through a mechanism that is incompletely understood. OBJECTIVE: The objective of this study was to determine the effects of pet exposure and genotype on immunologic development and the incidence of atopic markers and diseases in the first year of life. METHODS: Pet exposure in the home was compared with cytokine secretion patterns (mitogen-stimulated mononuclear cells at birth and age 1 year) and indicators of atopy (allergen-specific and total IgE, eosinophilia, food allergy, atopic dermatitis) in 285 infants. Interactions with genotype at the CD14 locus were also evaluated in the data analyses. RESULTS: Exposure to dogs was associated with reduced allergen sensitization (19% vs 33%, P =.020) and atopic dermatitis (30% vs 51%, P <.001). The risk for atopic dermatitis was further influenced by genotype at the CD14 locus (P =.006), even after adjusting for exposure to dogs (P =.003). Furthermore, infants with the genotype -159TT were less likely to develop atopic dermatitis if they were exposed to a dog (5% vs 43%, P =.04). Last, dog exposure was associated with increased IL-10 (117 vs 79 pg/mL, P =.002) and IL-13 (280 vs 226 pg/mL, P =.013) responses at age 1 year. CONCLUSIONS: Having a dog in infancy is associated with higher IL-10 and IL-13 cytokine secretion profiles and reduced allergic sensitization and atopic dermatitis. These findings suggest that postnatal exposure to dogs can influence immune development in a genotype-specific fashion and thereby attenuate the development of atopy in at-risk children.

Adult↗