Psychotherapy--an active agent: assessing the effectiveness of psychotherapy and its curative factors

This study was designed to investigate the clinical role of specific IgG4 and IgE responses in patients during immunotherapy for seasonal allergy. The study included 109 patients with seasonal allergic rhinitis due to Japanese cedar pollens. They were divided into the control group and the immunotherapy group. Serum samples were obtained at the start of immunotherapy, before the pollen season and during the season, to determine serum specific IgE and IgG4. In the control group specific IgE was significantly increased, but specific IgG4 was not changed during the pollen season. In the immunotherapy group specific IgE was not significantly increased, but specific IgG4 was significantly increased during the season. In the patients having immunotherapy for 2 years or less, the seasonal increase in specific IgG4 related to the magnitude of the clinical effect. In the patients having immunotherapy for 3 years or more, the seasonal increase in specific IgE related to the magnitude of the clinical effect. In conclusion, the specific IgG4 response and specific IgE response during the pollen season make a significant contribution to the clinical effect of immunotherapy. However, modulation of specific IgE and IgG4 responses out of the pollen season was unlikely to be an important phenomenon related to the clinical effect of immunotherapy.     

Immunotherapy with the storage mite lepidoglyphus destructor

We carried out a double-blind clinical trial of immunotherapy on 35 patients sensitized to the storage mite Lepidoglyphus destructor (Ld). Before and after 12 months of specific hyposensitization (Abelló Lab., Spain) we performed in vivo (skin tests with Ld, methacholine and challenge tests), and in vitro tests (specific IgE, IgG, IgG1 and IgG4 to Ld and specific IgE, IgG, IgG1 and IgG4 to their major allergen Lep dI). We also monitored the efficacy and safety of the immunotherapy with clinical and analytical controls (symptoms and medication score, detection of immune complexes). After therapy we found a significant decrease in specific skin reactivity, dose of positive challenge tests, and hyperresponsiveness to methacholine. Sputum eosinophilia decreased. Specific IgE to Ld was increased and we also observed an increase in specific IgG1 and IgG4 to Ld and Lep DI. The placebo group showed no changes in these variables. There were no severe secondary reactions after treatment with the extract. Patients-self-evaluation was favourable and their labour absence decreased. No development of circulating immune complexes was associated with this immunotherapy.     

Specific immunotherapy--past--present--future

Specific immunotherapy or hyposensitization has been used extensively for almost 90 years as a specific treatment of IgE-mediated allergic diseases. In hayfever and allergic asthma due to house-dust mites and animal danders (especially cat) immunotherapy is highly effective and used worldwide. The term "local immunotherapy" stands for topical administration of specific IT in allergic disorders and includes local nasal, bronchial, oral and sublingual immunotherapy. Today bronchial and oral IT can not yet be recommended for clinical practice. Local nasal IT may be indicated in carefully selected adult patients with rhinitis caused by grass- and Parietaria-pollen allergy. Sublingual (swallow) IT with pollen (Grass/Parietaria) and mite extracts can be recommended in adult patients with allergic rhinitis.     

Immunogenicity of casein phosphopeptides derived from tryptic hydrolysis of beta-casein

The immunogenicity of phosphopeptides derived from tryptic hydrolysis of beta-casein (CN) was investigated in a rat model system. The titers of specific immunoglobulin (Ig)G and IgE antibodies made in response to intraperitoneal sensitization to beta-CN, casein phosphopeptides, and skim milk proteins were examined using indirect and amplified indirect ELISA, respectively. Serum IgG antibodies from rats injected with beta-CN were significantly more reactive to beta-CN, casein phosphopeptides, and skim milk proteins coated on microtiter plate wells than were the IgG antibodies generated in rats that had been subjected to other treatments. A significant difference in titers because of the time of sampling (14 or 21 d postinjection) was noted for IgE but not for IgG. Rats that were injected with casein phosphopeptides did not produce IgG antibodies that crossreacted with either skim milk proteins or beta-CN. Specific antibody levels for the IgE class rarely exceeded those of unimmunized controls. The findings suggest that immunogenicity of the phosphopeptides was reduced compared with that of native beta-CN and skim milk proteins.     

Anaphylactic IgE and IgG1 production for hapten can be enhanced by contrast media

Various side effects have been associated with the clinical use of contrast media. Immunological mechanisms have been proposed but there have been very few experimental studies with animal models. We have attempted to develop murine models to determine whether or not anaphylactic antibodies such as IgE and IgG1 against hapten (DNP) were enhanced with contrast medium (iopamidol) as an adjuvant or if the contrast medium itself produced antibodies of the IgE class. The results showed that anti-hapten IgE and IgG1 production was greatly enhanced with immunogen plus contrast medium. Anti-contrast medium antibodies of the IgE class could not be detected by PCA reactions. The enhancement of IgE and IgG1 production for hapten was associated with IL-4 release by the neutralization test used by monoclonal anti-IL-4 antibodies. This is the first observation to show that contrast media may have a strong adjuvant effect for the production of IgE and IgG1. This murine model demonstrates a possible immunological function of contrast media in vivo.     

Placebo-controlled immunotherapy with Cocos nucifera pollen extract

The effectiveness of Cocos nucifera pollen extract immunotherapy (CPE-IT) was studied in 96 patients allergic to C. nucifera pollen. A placebo-controlled study was performed at random for a period of 6-12 months. The clinical status of the patients measured by the symptom-medication scores demonstrated that C. nucifera pollen-allergic patients had significant (p < 0.005) clinical improvement after CPE-IT in comparison to placebo treatment. Serological study resulted a significant reduction (p < 0.001) of specific IgE and significant elevation (p < 0.01) of specific IgG in post-therapeutic patients' sera which were correlated significantly (r = 0.45, p < 0.001); the changes of the above immunoglobulin levels in the placebo-treated patients were nonsignificant. However, there was no correlation between symptom-medication scores and changes in specific serum IgE or IgG levels.     

Perceptual organization in schizophrenia: utilization of the Gestalt principles

BACKGROUND: Allergen immunotherapy results in a number of changes in clinical, inflammatory, and immunologic parameters. However, the basis for the specificity of this form of therapy is unknown, especially in the context of changes in T- and B-lymphocyte function after desensitization to specific allergens. OBJECTIVE: This study was designed to determine the immunologic consequences of rush immunotherapy. METHODS: We studied 10 patients who had positive skin test responses to the house dust mite Dermatophagoides pteronyssinus (Dpt) and cat dander extract. Each received rush immunotherapy to mite, but not cat dander, over a 2- to 4-week period until maintenance was achieved. Patients were evaluated before and when maintenance was achieved for skin test and nasal reactivity to mite and cat dander; antibody levels to the allergen were monitored, as were lymphocyte proliferative responses and cytokine production. RESULTS: Rush immunotherapy to house dust mite resulted in a significant reduction in skin and nasal reactivity to mite allergen, but not to cat allergen, in 10 of 10 patients. This was accompanied by a rise in serum anti-Dpt IgE, whereas anti-cat IgE was not altered (7 of 7 patients). In seven of seven patients there was an increase in anti-Dpt IgG4 levels. T-cell proliferative responses to mite antigen were suppressed, and numbers of CD8+ T cells increased in frequency. There was a marked increase in interferon-gamma production, particularly by CD4+ T cells in 10 of 10 patients. The correlation between the increases in interferon-gamma production and the changes in cutaneous reactivity was highly significant. CONCLUSION: We show that rush immunotherapy is immunologically specific in eliciting changes in T- and B-cell responses to the desensitization antigen. The specificity and potential benefit of immunotherapy may be linked to the increase in interferon-gamma production by allergen-activated CD4+ T lymphocytes.     

Oral dosing of rats with OM-89 results in the appearance of specific OM-89 antibodies of the IgG2a isotype: possible significance in the treatment of rheumatoid arthritis

OM-89 is a glycoprotein-rich extract of Escherichia coli shown to be effective in the treatment of rheumatoid arthritis (RA). It has been reported that oral dosing of animals results in the appearance of specific OM-89 antibodies. In the current study we have investigated some of the immunoglobulin isotypes that may be involved. OM-89 antibodies of IgG1, IgG2a and IgM isotypes were measured by ELISA in serum from rats dosed three times a week for 3 weeks at 4 or 40 mg kg(-1). The results showed a small but significant rise in IgM and a greater rise in IgG2a. The possibility that antigens within OM-89 (e.g. hsp65) may have homology with antigens involved in RA raises the possibility that OM-89 antibodies, particularly of the IgG2 class, may block pathogenic antigens from being recognized by T cells.     

Evaluation of risk and diagnostic value of quantitative assays for anti-Toxoplasma gondii immunoglobulin A (IgA), IgE, and IgM and analytical study of specific IgG in immunodeficient patients

To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects, we assayed immunoglobulin A (IgA) and IgE antibodies by means of immunocapture (IC) tests, with revelation done by using a suspension of T. gondii (ICT). We also carried out a simultaneous analytical study of IgG antibodies on cellulose acetate membranes by using the comparative immunological profile method and an enzyme-linked immunofiltration assay (ELIFA). A total of 1,238 samples (serum, cerebrospinal fluid, and aqueous humor from 318 patients) were tested. IgA and IgE antibodies were detected in all heart, kidney, and liver transplant recipients with clinical manifestations of toxoplasmosis; IgA was detected in the aqueous humor of a patient with chorioretinitis. In patients with AIDS-related toxoplasmosis, including the cerebral form, IgA and IgE antibodies or a significant modification of ELIFA IgG values were observed in 38, 19, and 25% of patients, respectively. IgM was detected by ICT only in 12% of patients and aided the diagnosis in 1 of 71 patients. IC tests for specific IgA and IgE alone and combined with ELIFA were positive in 39 and 46% of patients who developed clinical toxoplasmosis, respectively. In a serial study of 16 patients in whom at least one of these three tests was positive, a significant immunological signal sometimes preceded clinical onset by 1, 6, and even 17 months. Similarly, in a group of human immunodeficiency virus-infected patients with evidence of previous exposure to T. gondii but no clinical manifestations, IgA, IgE, and IgA and/or IgE antibodies were detected in only 11, 4, and 12% of patients, respectively. These two situations point to peripheral T. gondii reactivation. IgA and IgE emerged as interesting markers of the risk of toxoplasmosis in immunodepressed patients. They may also provide valuable assistance in the diagnosis of toxoplasmosis, especially because tests for specific IgM are disappointing. However, at least one in two patients with toxoplasmosis showed no detectable immunological reaction, suggesting that this polyisotypic approach should be combined with other noninvasive methods such as gene amplification.     

Enhanced in vitro tumor cell retention and internalization of antibody derivatized with synthetic peptides

Human IgG subclasses play a major role in the physiological regulation and functions of the immune system. There "personality" is obvious. However, the determination requires appropriate reagents and technology. For the IgG1, IgG2, IgG3 subclasses, the radial immunodiffusion technique may be sufficient. For the IgG4 subclass determination and measurement, more elaborate techniques are required. These measurements of existing proteins are of major interest in congenital as well as acquired immune deficiencies more often, besides the total subclass deficiency, these are of utmost interest to evaluate the specific response of a given subclass to a specific antigen. The IgG4 allergen specific subclass has been considered to be involved both in allergic reactions and associated with the appropriate response to allergen-specific immunotherapy. It is now accepted that IgG4 does not play an discernable role in the acute inflammatory response of type I hypersensitivity; it has also been demonstrated that a number of patients who demonstrate elevated levels of allergens specific IgG4 are not protected against allergenic exposure, and conversely, a number of patients who have been heated by immunotherapy without demonstrating any significant increase in their serum levels of allergen specific IgG4 are indeed very well protected. In the field of allergy, the IgG4 determinations remain a matter of controversy and research.     

L-deprenyl as an adjunct to low-dose bromocriptine in early Parkinson''s disease: a short-term, double-blind, and prospective follow-up study

The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a synthetic peptide of its C terminus. When allergen and antibodies were allowed to preincubate, Lol p I induced histamine release was inhibited up to 85% by the antiserum against Lol p I. By omitting preincubation, and thereby more closely mimicking an in vivo situation, up to 55% inhibition was realized. This indicates that allergen-specific IgG can act as 'blocking' antibody without preincubation. Immunization of rabbits with a synthetic C-terminal peptide of Lol p I resulted in antibodies reactive with natural Lol p I. Despite their 100-fold lower avidity for Lol p I (as compared with antinatural Lol p I), these antibodies had the capacity to inhibit Lol p I induced histamine release for > 90% (up to 50% without preincubation). This indicates that it is possible to block histamine release induced by a major allergen with low-avidity IgG antibodies directed against a minor proportion of the allergen (25 amino acids). IgE antibodies from the donors studied were unreactive with this synthetic peptide, indicating that for blocking activity identical epitope specificity of IgE and IgG is not essential. This opens interesting perspectives for application of synthetic peptides in immunotherapy, distinct from their effects on T cell reactivity.     

Changes of acid phosphatase activity of fast and slow rat muscles during ontogenetic development

Total IgG, IgG subclass and IgE antibodies specific for grass pollen allergens were measured by the red cell linked antigen-antiglobulin reaction (RCLAAR) in a serum samples from nineteen patients who had undergone a course of hyposensitization. Increases in both specific IgG and IgE antibodies were seen after treatment in most patients. In the IgG subclasses the predominant response was for IgG1 and IgG4 antibodies. Attempts were made to correlate the antibody responses with the clinical response and the results are discussed with reference to the possible mechanisms of hyposensitization.     

Relationship between antigen and antibody-induced suppression of IgE antibody formation in the rat

Formation of specific IgE antibodies as elicited in Sprague-Dawley rats against Ascaris antigen could be suppressed by intravenous administration both of antigen and of specific antiserum. The suppressive agent in the antiserum was shown to be antibodies of the IgG class, whereas a suppressive effect of cytophilic activity and of IgE antibodies could be outruled. Suppression of IgE response lasted the longer the more antibodies were transferred. An antibody-induced suppression was achieved when antibodies were transferred during an early period (day -3 to day +8), whereas an antigen-induced suppression took place when the antigen was intravenously administered following the antibody-sensitive period (day +8 until day +14). This is consistent with the fact that an antigen-induced suppression of IgE formation requires the presence of a certain amount of antibodies. A strictly peripheric suppression could be outruled, since with elapse of time a decreasing dose of antigen was required to induce a suppression. The results are discussed on the basis of an antigen-antibody complex-induced suppression in the IgE system and its possible central site of action.     

Linear monitoring of patients sensitive to Olea and grass pollens treated with immunotherapy based on glutaraldehyde-modified (allergoid) extracts

Extracts modified with glutaraldehyde (allergoid) have been offered to allergologists for immunotherapy in the last few years as supposedly clinically effective agents that diminish undesirable side-effects (allergenicity vs. immunogenicity). In order to acquire experience in the use of this therapeutic resource, we monitored a group of patients with pollinosis sensitive to Olea, grass pollens or both, who suffered from seasonal rhinoconjunctivitis (SRC) or rhinoconjunctivitis and seasonal asthma (RCSA) and were administered allergoid treatments standardized in biological units (HEP). The patients were monitored by determination of specific IgE and IgG4, endpoint prick tests and conjunctival provocation tests (CPT) with two types of antigen: Lolium perenne and Olea europaea. Measurements were made at baseline (T1), when the maximal tolerated dose had been given (T2) and 1 year after the treatment was started (T3). According to our results, this type of extract is tolerated quite well and causes no alterations in specific IgG4 or IgE levels. On the other hand, it features significantly decreased allergen-specific skin reactivity and increased response thresholds to the CPT (p < 0.01). A high correlation between skin and conjunctival provocation tests was observed at some stages (r = 0.79, p < 0.01).     

Effect of pharmacist''s instruction on the treatment of asthmatics with inhaled steroid

BACKGROUND: The clinical efficacy and safety of local nasal immunotherapy (LNIT) with lyophilized 'macronized' powder has been demonstrated. However, the immunological changes possibly induced by LNIT which may account for the clinical improvement are still unclear. OBJECTIVE: To investigate the effects of a successful LNIT-treatment on the allergen-driven T cell response, cytokine secretion and IgE and IgG antibody production. METHODS: Three groups (untreated, subcutaneous immunotherapy- SIT- and LNIT-treated) of grass-sensitive patients suffering from seasonal rhinitic symptoms were ramdomized for the 2-year study. The proliferative response of PBMC to purified Rye-1 allergen and serum levels of grass-specific IgE and IgG were evaluated before treatment and during the 2-year subsequent pollination periods. The proliferative response of allergen-specific short-term T-cell lines, as well as production of allergen-driven cytokine by PBMC, were also assessed. RESULTS: Both SIT and LNIT induced a significant reduction of symptom scores during the pollination season. SIT, but not LNIT, induced a significant change in serum levels of allergen-specific IgE and IgG antibody. By contrast, both SIT and LNIT reduced the increase of the proliferative response of allergen-specific T cells driven by natural allergen exposure and significantly decreased T cell proliferation to low doses of allergen, as shown also by the mitogenic index of allergen-specific T-cell lines. A reduced IL-4 and IFNgamma production by PBMC of LNIT- and SIT-treated patients was also observed in the absence of a clearcut TH2-TH1 switch. CONCLUSIONS: These data suggest that a common mechanism of both LNIT and SIT is the induction of T-cell tolerance, thus providing a rational basis to explain why LNIT may be clinically successful in allergic patients with rhinits.     

The non-specific binding of immunoglobulins to silicone implant materials: the lack of a detectable silicone specific antibody

Recent studies have suggested that anti-silicone antibodies develop in patients implanted with silicone materials. The majority of these studies have utilized enzyme-linked immunosorbent assay (ELISA) methodology with a silicone material substrate as a means to detect the presence of the anti-silicone antibody. The current studies were undertaken to determine whether the binding of IgG to a silicone substrate was consistent with an antigen-specific antibody interaction or the result of non-specific hydrophobic interactions. While significant differences were detected in serum from silicone antibody "positive" and "negative" patients when the ELISA was conducted using a phosphate buffered saline (PBS)-0.05% Tween 20 (Tween) blocking system, the difference in the responses was attenuated when protein blocking systems were used or when incubation times were decreased. Furthermore, ELISA studies, using purified mouse and human IgG, demonstrated a concentration-dependent binding of IgG to silicone elastomer substrate which was also attenuated when a protein blocking system was used in lieu of Tween. In controlled animals studies in which female B6C3F1 mice were implanted with silicone gel or silicone elastomer for 180 days, no difference was observed between the implanted animals and the PBS control animals with respect to binding of IgG to the silicone substrate. Similar studies in female Fischer 344 rats implanted with silicone gel for 84 days also failed to demonstrate the presence of anti-silicone antibody. Collectively, the results suggest that the binding of IgG to silicone implant materials is non-specific in nature, consistent with the well-recognized interactions between hydrophobic molecules (IgGs) and hydrophobic surfaces (silicones) in an aqueous-based system.     

Human IgG monoclonal antibodies that modulate the binding of specific IgE to birch pollen Bet v 1

Birch pollen allergy is a very frequent pathology in Europe and North America. More than 95% of the tree pollen allergic patients display IgE reactivity against Bet v 1, the major birch pollen allergen. Starting with PBL from a patient desensitized by immunotherapy, we have generated five B cell lines (BAB1 to BAB5) that secrete human IgG mAbs of high affinity for Bet v 1. Although competition studies indicated that these human IgG mAb recognized different epitopes, broad cross-reactivity was found with Bet v 1 homologous allergens present in tree pollens and plant-derived foods. When tested for interference with allergic patients' IgE, BAB1 inhibited (by 80-100%) the binding of IgE to nitrocellulose-blotted Bet v 1, while BAB2 enhanced it. The biologic significance of the ability of BAB1 to interfere with patients' IgE binding is indicated by the finding that BAB1 completely inhibited Bet v 1-induced histamine release from allergic patients' basophils. Allergen-specific human IgG mAbs such as BAB1, which presents high blocking activity in both immunochemical and cellular IgE competition experiments, might have therapeutical application.     

Antigen-independent suppression of the IgE immune response to bee venom phospholipase A2 by maternally derived monoclonal IgG antibodies

The IgE immune response to ovalbumin in rats can be suppressed by prior immunization of the dams. The results reported in this paper extend this observation to include a different antigen and another species, namely the IgE immune response to bee venom phospholipase A2 (PLA2) in CBA/J mice. The degree of suppression seemed to depend on the amount of IgG antibodies transferred to the offspring. Moreover, we found that the maternally mediated suppression of the IgE response could be achieved in a completely antigen-free system in which exogenous monoclonal anti-PLA2 IgG antibodies were transferred from the dams to the offspring. The following results were obtained: (i) The IgE suppression by monoclonal IgG antibodies was induced as efficiently with one single anti-PLA2 IgG1 antibody as with a mixture of ten antibodies (nine IgG1, one IgG2b). (ii) Even after several immunizations up to an age of 6 months with a dose of PLA2 that normally induces IgE production, none of the F1 mice developed an IgE response. (iii) This long-lasting suppression was observed in mice which were first immunized at an age of 4 weeks (i.e. when low amounts of maternally derived monoclonal IgG were still present), as well as in mice which were first immunized at an age of 8 weeks, when no such maternal antibodies could be detected in their sera. The corresponding IgG responses showed, compared to normal mice, a transient enhancement in the maternally influenced mice. It is concluded that the immunological experience of the mother is of particular importance for the isotype regulation in the newborns, especially with respect to the ability to elicit an IgE response. The possible implications for the development of allergic diseases in humans are discussed.     

Factors influencing immediate responses to intradermal allergen administration in patients with respiratory allergy

BACKGROUND: Immediate skin reactions to allergens are influenced by several factors, such as the amount of administered allergen, the level of specific IgE, releasability of mast cells and hyperresponsiveness of the target organ. METHODS: For the evaluation of factors influencing immediate skin response to intradermal allergen administration, we measured the wheal size 15 min after intradermal injection of 0.01-0.02 ml of the following agents: whole-body extract of Dermatophagoides farinae, 1,000 allergy units/ml; histamine, 0.1 mg/ml, and codeine sulfate, 0.09% in saline, and determined total IgE level, specific IgE and IgG subclass antibodies to D. farinae in 53 patients with respiratory allergy. RESULTS: Multiple regression analysis for factors influencing wheal size after intradermal injection of D. farinae, specific IgE antibody level to D. farinae and wheal size after intradermal administration of histamine showed statistically significant results (R2 = 0.42739, p = 0.0000; R2 = 0.50243, p = 0.0185, respectively). Multiple regression analysis for factors influencing wheal size after intradermal administration in the group with high levels of specific IgE to D. farinae (RAST class 3 or more) showed that wheal size after intradermal administration of codeine was the only factor exerting a statistically significant influence (p = 0.0119). CONCLUSION: Based on the above results, we can state that immediate responses to intradermal allergen administration were influenced by the level of specific IgE and hyperresponsiveness of the target organ to histamine, but that the immediate skin allergic responses in the presence of high levels of specific IgE were partially but significantly influenced by the releasability of skin mast cells.     

Serologic study of the working mechanisms of immunotherapy for children with perennial allergic rhinitis

BACKGROUND: Recent double-blind placebo-controlled trials have clearly shown the efficacy of immunotherapy for perennial allergic rhinitis. However, the exact working mechanisms related to the clinical effect of immunotherapy remain unclear. OBJECTIVES: To monitor the changes over time in immunologic parameters in children who received immunotherapy for perennial allergic rhinitis, and to elucidate the working mechanisms of immunotherapy related to its clinical efficacy. DESIGN: Nineteen children with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective open study. Venous blood was collected to determine levels of specific IgE, specific IgG4, soluble interleukin 2 receptor, interleukin 4, soluble intercellular adhesion molecule 1, and soluble vascular cell adhesion molecule 1 at enrollment and 1, 2, 3, 5, and 10 years after enrollment. RESULTS: Immunotherapy affected serum levels of specific IgE, specific IgG4, soluble interleukin 2 receptor, interleukin 4, and soluble intercellular adhesion molecule 1, but not soluble vascular cell adhesion molecule 1. The rates of increase of levels of specific IgG4 and the rates of decrease of levels of soluble interleukin 2 receptor were correlated with the rates of decrease of symptom scores during the first 3 years of treatment, but not after 5 years. The rates of decrease in levels of soluble intercellular adhesion molecule 1 were correlated with the rates of decrease in symptom scores at 3 and 5 years after the beginning of the course of immunotherapy. The rates of decrease in levels of specific IgE and interleukin 4 were correlated with the rates of decrease in symptom scores after 5 and 10 years of treatment, but not during the first 3 years. CONCLUSION: Each modulation in levels of specific IgE, specific IgG4, soluble interleukin 2 receptor, interleukin 4, and soluble intercellular adhesion molecule 1 contributed to the clinical effect of immunotherapy in particular phases of treatment for children with perennial allergic rhinitis.