Changes of House Dust Mite-Specific IgE, IgG and IgG Subclass Antibodies during Immunotherapy in Patients with Perennial Rhinitis

Nakagawa, Takemasa; Kozeki, Hiroo; Katagiri, Junichi; Fujita, Yosuke; Yamashita, Naomi; Miyamoto, Tomofumi; Skvaril, F

doi:10.1159/000234297

Cited by 54 publications

(33 citation statements)

References 14 publications

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“…It was previously postulated that immunotherapy could decrease IgE synthesis, but this reduction did not occur within a few years of immunotherapy [4,24,25]. Our previous study also failed to show any early decrease in specific IgE levels even in patients who responded well to immunotherapy [26].…”

Section: Discussioncontrasting

confidence: 57%

“…Several lines of experimental evidence suggest that specific IgG4 could act in vitro as a blocking antibody to inhibit IgEmediated immunological reactions on the surface of mast cells [18,19], and immunotherapy can increase specific IgG4 in serum of patients on immunotherapy [4,5,26]. However, there is no general agreement among different investigators regarding the clinical role of specific IgG4 during immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is no general agreement among different investigators regarding the clinical role of specific IgG4 during immunotherapy. Some authors claimed that an elevation of specific IgG4 contributed to the clinical efficacy of immunotherapy [4,5,26]. By contrast, others argued that specific IgG4 might not play a clinical role in immunotherapy but be simply a marker of antigen exposure following subcutaneous injections, because they could not confirm any causal relationship between the clinical effect and an increase in specific IgG4 in serum [6,7].…”

Section: Discussionmentioning

confidence: 99%

“…Allergen-specific immunoglobulin (Ig)E and IgG, especially the blocking antibody of IgG4, were previously believed to be of key importance in allergic rhinitis, and considerable attention was devoted for decades to the role of specific IgE and IgG4 in serum relation to clinical outcome. However, there is no definite conclusion regarding these antibodies, because an increase in specific IgG4 was associated with a good clinical efficacy of immunotherapy in some studies [4,5] whereas this association was not confirmed in others [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Ten‐Year Follow‐Up Study of Allergen‐Specific Immunoglobulin E and Immunoglobulin G4, Soluble Interleukin‐2 Receptor, Interleukin‐4, Soluble Intercellular Adhesion Molecule‐1 and Soluble Vascular Cell Adhesion Molecule‐1 in Serum of Patients on Immunotherapy for Perennial Allergic Rhinitis

et al. 1998

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Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrolment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ten‐Year Follow‐Up Study of Allergen‐Specific Immunoglobulin E and Immunoglobulin G4, Soluble Interleukin‐2 Receptor, Interleukin‐4, Soluble Intercellular Adhesion Molecule‐1 and Soluble Vascular Cell Adhesion Molecule‐1 in Serum of Patients on Immunotherapy for Perennial Allergic Rhinitis

et al. 1998

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“…Despite such recent developments of hyposensitization therapy, its precise mechanism has remained elusive. It was previously thought that loss of a seasonal rise in serum IgE antibody levels and/or the formation of IgGblocking antibodies mediated hyposensitization of various allergic diseases [3][4][5]. Although a significant overall association between changes of antibody levels after hyposensitization and clinical effects has been found, there are always a considerable number of exceptions [6,7].…”

Section: Introductionmentioning

confidence: 99%

Hyposensitization Attenuates Airway Inflammation and Antigen-Induced Proliferative Response by Lymphocytes in a Rat Model of Bronchial Asthma

Ohnuma

Yamaguchi²,

Oguri³

et al. 1998

Respiration

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The mechanism of hyposensitization in bronchial asthma has not been fully elucidated. We established a hyposensitization model of bronchial asthma in rats and examined airway responses and immunological parameters. Brown Norway rats were sensitized by a subcutaneous injection of ovalbumin (OA) at day 1 and by the inhalation of 2% OA aerosol at day 15. Animals were hyposensitized by intraperitoneal injections of OA from day 17 to day 22. They were challenged with OA or acethylcholine (Ach) aerosol at day 23 and changes in intratracheal pressure were recorded. Lungs were lavaged and OA-induced proliferative responses by blood lymphocytes were examined for animals without aerosol challenge at day 23. OA-specific serum IgE levels were measured by enzyme-linked immunosorbent assay. Hyposensitization significantly reduced the OA-induced immediate airway response, accumulation of CD4+ lymphocytes and eosinophils recovered by bronchoalveolar lavage, and the OA-induced proliferative response by blood lymphocytes. The airway responses to Ach and serum OA-specific IgE levels in hyposensitized group were not significantly different from those in the sensitized group. These results indicate that amelioration of airway inflammation and hyporesponsiveness of lymphocytes against OA are involved in the attenuated immediate antigen-induced airway response following hyposensitization.

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Clonally related IgE and IgG4 transcripts in blood lymphocytes of patients with asthma reveal differing patterns of somatic mutation

et al. 1998

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Isotype switching to IgE contributes to atopic asthma, therefore strategies to divert this process to alternative isotypes could have therapeutic relevance. It is known that patients with allergic disease have serum IgE and IgG4 antibodies with similar specificities, and that cytokines such as IL-4 mediate switching to both of these isotypes. Availability of variable region gene analysis has allowed us to probe isotype variants at the single-cell level. An earlier report described identification in a single atopic patient of short transcripts with a common complementarity-determining region "clonal signature" in combination with C mu, C gamma4 and C epsilon. We have extended this analysis, and have identified V(H)-Cgamma4 transcripts with clear clonal relationship to IgE-derived sequences in blood lymphocytes from three of four patients with atopic asthma. No other IgG subclasses were detected, confirming the link between IgE and IgG4. Full sequences were obtained from each clonally related isotype in all patients, and showed extensive somatic mutation. As previously found for IgE, the IgG4 isotypes had evident intraclonal variation. There were shared mutations between isotypes, but also many differences, indicative of separate cell populations with divergent mutational histories. These findings indicate that, in atopic patients, an individual B cell commonly switches to either IgE or IgG4. Cells producing each isotype then co-exist in the recirculating pool, and the balance between them may influence the disease process.

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Changes of House Dust Mite-Specific IgE, IgG and IgG Subclass Antibodies during Immunotherapy in Patients with Perennial Rhinitis

Cited by 54 publications

References 14 publications

Hyposensitization Attenuates Airway Inflammation and Antigen-Induced Proliferative Response by Lymphocytes in a Rat Model of Bronchial Asthma

Clonally related IgE and IgG4 transcripts in blood lymphocytes of patients with asthma reveal differing patterns of somatic mutation

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