Pet ownership: its effect on allergy and respiratory symptoms.

BACKGROUND: Studies have shown that pets are very important sensitizing agents in patients with asthma. Respiratory disorders such as asthma and allergic rhinitis are common in the State of Qatar. OBJECTIVE: The aim of the present study was to determine whether exposure to pets and domestic animals plays a significant role in the development of asthma and allergic rhinitis among Qatari population. DESIGN: A hospital-based prospective descriptive study conducted. SETTING: Allergy Laboratory at the Hamad General Hospital and Hamad Medical Corporation, State of Qatar. PATIENTS: Adult patients over 12 years of age diagnosed with bronchial asthma and/or allergic rhintis who were referred for allergy skin prick test. 1106 adult patients recruited with respiratory diseases of suspected allergic origin who attended Allergy Clinic at the Hamad General Hospital, during three years from January 2001 to April 2003. Total of 1106 whom 607 were females (54.9 %) and 499 were males (45.1%) and their mean was age 30 years (12-48). METHODS: Skin Prick Test (SPT) was performed on 1106 patients for common allergens whom the blood sample was taken for measuring total IgE concentration. RESULTS: There were 1106 patients studied and 496 patients (44.9%) had positive and 610 (55.1%) had negative skin prick tests. Out of 1106 patients, 311 patients (28.1%) had asthma; 503 patients had allergic rhinitis (45.5%) and 87 patients (7.8%) had skin allerg. Three hundred and forty (340/1106=30.7%) of the 1006 subjects studied had at least one animal at home, and the remaining 69.3% had never had pets in the home. A further 12% reported having had pets in the past, but not anymore. Cats (26.7%), goats (15%) and birds (14.7%), animals were the most common present within the house and was the most frequently seen pet types when compared to other pet types. The risk of having asthma (RR: 1.29; 95% CI: 1.07-1.55; p=0.008), allergic rhinitis (RR: 1.48; 95% CI: 1.24-1.77; p<0.0001) and eczema (RR: 3.56; 95% CI:1.24-1.77; p<0.0001) was significantly higher in subjects with animals than in patients without. CONCLUSION: In the present study, the prevalence of asthma, rhinitis, and skin allergy was significantly more common in families with animals than in those without.

An anti-murine CD3 monoclonal antibody with a low affinity for Fc gamma receptors suppresses transplantation responses while minimizing acute toxicity and immunogenicity.

145-2C11, a hamster mAb directed against the mouse CD3 complex, is a potent immunosuppressive agent. Upon initial treatment, 145-2C11 triggers a systemic release of multiple cytokines that is responsible for the acute toxicity of the mAb. This cellular activation is a consequence of the cross-linking between T lymphocytes and Fc gamma R-bearing cells, mediated by the high affinity of the hamster mAb for murine Fc gamma Rs. Repeated mAb injections result in the onset of a neutralizing humoral response. Therefore, there has been an increased interest in developing nonmitogenic forms of anti-CD3 mAbs, although it is not clear whether these Abs will retain immunosuppressive properties. To determine whether the initial cytokine production is necessary for the immunosuppressive properties and the immunogenicity of anti-CD3 mAbs in vivo, we have generated chimeric (hamster 145-2C11 F(ab')2 region/mouse Fc gamma portion) mAbs using murine isotypes with different affinities for Fc gamma Rs. The 145-2C11 and a chimeric IgG2a isotype, both of which bind murine Fc gamma Rs avidly, had similar activating, immunogenic, and immunosuppressive properties in mice. The administration of a chimeric IgG3 isotype with a very low affinity for murine Fc gamma Rs did not result in cytokine production, a humoral response against the mAb, or TCR desensitization. Nevertheless, prolongation of skin graft survival was similar in the IgG3, IgG2a, and 145-2C11-treated mice, indicating that Fc gamma R nonbinding anti-CD3 mAbs retain potent immunosuppressive properties in vivo while not being immunogenic. This enhanced therapeutic to toxic profile may be beneficial in clinical transplantation.

A non-activating "humanized" anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo.

OKT3, a mouse anti-human CD3 mAb, is a potent immunosuppressive agent used in clinical transplantation to prevent or treat allograft rejection. Associated with this therapy is the systemic release of several cytokines that result in a series of adverse side effects. This release of cytokines is dependent on the cross-linking mediated by OKT3 between T cells and the Fc gamma R-bearing cells. To generate an anti-human CD3 mAb with reduced activating properties as compared with OKT3, we have transferred the complementary determining regions of OKT3 onto human IgG frameworks and then performed point mutations that reduce the affinity of the "humanized" anti-CD3 mAbs for Fc gamma Rs. Initial, in vitro, studies showed that whereas OKT3 and the parental humanized anti-CD3 mAbs activated T cells similarly, a humanized Fc variant failed to do so. Both the Fc variant and the activating anti-CD3 mAbs induced comparable modulation of the TCR and suppression of cytolytic T cell activity, in vitro. In the current study, we exploited an experimental model in which human splenocytes from cadaveric organ donors were inoculated into severe combined immunodeficient mice (hu-SPL-SCID mice) to test the activating and immunosuppressive properties of these anti-human CD3 mAbs in vivo. Unlike injection of OKT3 or of the parental humanized mAb, administration of the Fc variant did not result in T cell activation in vivo, as evidenced by the lack of induction of surface markers of activation, and of systemic human cytokines, including IL-2. Importantly, similar prolongation of human allograft survival was achieved with all anti-CD3 mAbs, indicating that the nonactivating anti-CD3 mAbs retained significant immunosuppressive properties in vivo. Thus, the use of an Fc variant in clinical transplantation should result in fewer side effects than observed with OKT3, while maintaining its clinical efficacy.

Prevention of the humoral response induced by an anti-CD3 monoclonal antibody by deoxyspergualin in a murine model.

Multiple treatments with the potent immunosuppressant murine antihuman CD3 mAb OKT3 is sometimes precluded by the onset of a neutralizing humoral response mostly consisting of anti-idiotypic antibodies. A hamster antimurine CD3 monoclonal Ab, 145-2C11, shares many properties with OKT3, in particular the ability to induce a strong Ab response in mice. Deoxyspergulain (DSG), a metabolite of the antibiotic spergualin, has been shown to reduce Ab production triggered by pathogens in a variety of infectious models and against common antigens. In this study, we examined the ability of DSG to inhibit the humoral response induced by 145-2C11. DSG prevented the Ab production triggered by the anti-CD3 mAb in an Ag-specific manner and significantly reduced the Ab production in mice previously primed with 145-2C11. We showed that DSG had a long-term effect on B cells and a transient effect on T cells. In effect, DSG was found to induce a prolonged Ag-specific unresponsiveness of B lymphocytes, and to transiently reduce the capacity of T lymphocytes to deliver help to B cells, in part by reducing IL-4 production. DSG did not reduce the immunosuppressive properties of the anti-CD3 mAb. In fact, the combination of DSG with 145-2C11 prolonged the survival of allogeneic skin grafts when compared with the administration of 145-2C11 or DSG alone. Thus, the coadministration of DSG with OKT3 may be of clinical interest to reduce the humoral response triggered by the mAb.