Year Of Specific Immunotherapy Research Articles

Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy

Allergic disease reflects specific inflammatory processes initiated by interaction between allergen and allergen-specific IgE. Specific immunotherapy (SIT) is an effective long-term treatment option, but the mechanisms by which SIT provides desensitization are not well understood. Our aim was to characterize IgE sequences expressed by allergen-specific B cells over a 3-year longitudinal study of patients with aeroallergies who were undergoing SIT. Allergen-specific IgE-expressing clones were identified by using combinatorial single-chain variable fragment libraries and tracked in PBMCs and nasal biopsy samples over a 3-year period with antibody gene repertoire sequencing. The characteristics of private IgE-expressing clones were compared with those of stereotyped or "public" IgE responses to the grass pollen allergen Phleum pratense (Phl p) 2. Members of the same allergen-specific IgE lineages were observed in nasal biopsy samples and blood, and lineages detected at baseline persisted in blood and nasal biopsy samples after 3 years of SIT, including B cells that express IgE. Evidence of progressive class switch recombination to IgG subclasses was observed after 3 years of SIT. Acommon stereotyped Phl p 2-specific antibody heavy chain sequence was detected in multiple donors. The amino acid residues enriched in IgE-stereotyped sequences from seropositive donors were analyzed with machine learning and k-mer motif discovery. Stereotyped IgE sequences had lower overall rates of somatic hypermutation and antigen selection than did single-chain variable fragment-derived allergen-specific sequences or IgE sequences of unknown specificity. Longitudinal tracking of rare circulating and tissue-resident allergen-specific IgE+ clones demonstrates persistence of allergen-specific IgE+ clones, progressive class switch recombination to IgG subtypes, and distinct maturation of a stereotyped Phl p 2 clonotype.

Specific immunotherapy with mugwort pollen allergoid reduce bradykinin release into the nasal fluid.

IntroductionA pathomechanism of allergic rhinitis is complex. A neurogenic mechanism seems to play a significant role in this phenomenon.AimThe evaluation of influence of specific immunotherapy of mugwort pollen allergic patients on the bradykinin concentration in the nasal lavage fluid.Material and methodsThe study included 22 seasonal allergic rhinitis patients. Thirty persons with monovalent allergy to mugwort pollen, confirmed with skin prick tests and allergen-specific immunoglobulin E, underwent a 3-year-long allergen immunotherapy with the mugwort extract (Allergovit, Allergopharma, Germany). The control group was composed of 9 persons with polyvalent sensitivity to pollen, who were treated with pharmacotherapy. Before the allergen-specific immunotherapy (AIT) and in subsequent years before the pollen seasons, a provocation allergen test with the mugwort extract was performed, together with collection of nasal fluids, where bradykinin concentration was determined according to Proud method.ResultsThere were similar levels of bradykinin in both groups at baseline prior to therapy (AIT group: 584.0 ±87.2 vs. controls 606.3 ±106.5 pg/ml) and changes after allergen challenge 1112.4 ±334.8 vs. 1013.3 ±305.9 pg/ml as well. The bradykinin concentration in nasal lavage fluid after mugwort challenge in 1 year was lower in the AIT group (824.1 ±184.2 pg/ml vs. 1000.4 ±411.5 pg/l; p < 005) with a further significant decrease after the 2nd and 3rd year of specific immunotherapy. Significant reduction of symptoms and medications use was observed in hyposensitized patients.ConclusionsA decreased level of bradykinin as a result of AIT suggests that some of the symptomatic benefits of AIT may be related to the reduced release of bradykinin into nasal secretions. These values correlate with clinical improvement within the course of treatment.

Component-resolved diagnostics in vernal conjunctivitis

BackgroundConventional diagnostic tests in allergy are insufficient to clarify the origin of vernal conjunctivitis (VC). ObjectivesTo evaluate IgE-mediated hypersensitivity by component-resolved diagnosis (CRD) in tears and serum from patients with VC and to evaluate how to treat patients with identified triggering allergens by specific immunotherapy. MethodsPatients were divided into 3 groups: (1) patients with VC (25 patients), (2) patients allergic to grass pollen with seasonal allergic conjunctivitis (AC) (50 patients), and (3) healthy blood donors (50 patients). If triggering allergens were detected, specific conventional immunotherapy was administered for 1 year. ResultsTwenty-five patients with VC were evaluated. The identified triggering allergens were n Lol p 1 (11 patients), n Cyn d 1 (8 patients), group 4 and 6 grasses (6 patients), and group 5 grasses (5 patients). Prick test and pollen IgE test results were positive in one patient. Clinical improvement was observed in 13 of the 25 patients with VC after 1 year of specific immunotherapy. ConclusionCRD seems to be a more sensitive diagnostic tool compared with prick test and IgE detection. Specific CRD-led immunotherapy may achieve clinical improvements in patients with VC.

Immunological changes after one year of specific immunotherapy with Pru p 3

Rationale In Southern Europe Pru p3 is the primary sensitizer of plants fruit and responsible for severe reactions. Specific immunotherapy (SIT) brings a new perspective to treat anaphylactic patients. There is a lack of knowledge regarding immunological response that includes changes in the basophil activation and antibody production during IT. We aimed to analyse early changes in the basophil response to Pru p 3 and another related allergen (Ara h 9) during the first year of sublingual immunotherapy (SLIT).

Anaphylaxis during specific subcutaneous immunotherapy against ragweed allergen ‐‐ case record

Recommended by Resolution of Immunotherapy, issued by EAACI, Specific immunotherapy (SIT) was established as a mainstream method of treating allergic diseases. SIT produces long term challenges. SIT team should be aware that at first injection of allergen, the immunotherapy may cause a long lasting reaction. Anaphylaxis during SIT is very rare, but it is possible. We've experienced anaphylaxis after four year of SIT, against ragweed allergen. A fifty four year old female went into anaphylactic shock after four years of SIT against ragweed allergen. Before the start of SIT, complete diagnostic procedures had been performed. Intradermal skin tests were performed for standard pallet of contact, inhalation, and nutritional allergens. The female patient tested positive for Ragweed (high positive), fungi (aspergillum fumigates, altenaria), and milk. Total IgE was measured using Enzyme Linked Immunoassay (ELISA). After injection of the SIT maintenance dose (0.2 ml of second concentration of allergen, (product of authorized Immunologic Laboratory Production) against ragweed, anaphylaxis developed within five minutes. The first manifestation was itchy palms and itching of eyes, followed by a rash. A dose of 0.0005 gram epinephrine was administered subcutaneously immediately. After the epinephrine injection, an IV rout was established with 0.9 % saline infusion, 0.2 gram of hydrocortisone, and 0.020 gram of chloropiramin was administered intramuscularly. No bronchoobstruction developed. Patient displayed anxiety. After an hour of treatment, the symptoms of anaphylaxis subsided. Anaphylaxis can develop as a complication of SIT with any possible manifestation. Treatment of anaphylaxis should start immediately after initial symptoms. The use of epinephrine is recommended.

Allergen Specific Immunotherapy in Cases of Severe Atopic Dermatitis

S U N D A Y 366 Allergen Specific Immunotherapy in Cases of Severe Atopic Dermatitis Inmaculada S anchez-Mach in, MD, Paloma Poza, Ruperto Gonz alez, Victor Matheu, MD; Hospital Ofra-T orax, Tenerife, Spain, Hospital Ofra-T orax, santa cruz de tenerife, Spain, Hospital Ofra-T orax, S/C de Tenerife, Spain, Hospital Ofra, Tenerife, Spain. RATIONALE: Allergen sensitization appears to be part of the etiology of Atopic Dermatitis (AD). The effectiveness of allergen specific immunotherapy (SIT) in AD remains controversial, even contraindicated in severe cases. METHODS: Total IgE (T-IgE) and Specific IgE (S-IgE) by CAPFarmacia. Patient 1 (P1): 43-year-old male. Patient 2 (P2): 31-year old woman. Patient 3 (P3): 9-year-old woman. All of them were nonresponders to usual therapeutics including corticosteroids oral (Last year daily for P1, P2, and 6 cycles for P3), cyclosporin (P1, P2) or methotrexate (P1with bloody diarrhea). They hadmild persistent rhinitis and intermitent asthma and positive S-IgE to Dermatophagoidesand storage mites, and P1 also to grass, ragweed pollen and foods without clinical relevance. RESULTS: In a first visit SCORAD and T-IgEwere: P1, 81 and 31,090UI/ ml. P2, 75 and 19,038UI/ml. P3, 36 and 14.897UI/ml.We started treatment with SIT, with cluster administration schedule of 4weeks in Hospital Immunotherapy Unit and subsequent monthly maintenance. The early months P1 and P2 showed improvement. The T-IgE was descending in improved patients to be in the 4 year of SIT: 5,560UI/ml for P1 and 2,500UI/ml for P2 with SCORAD of 11 and 5 respectively. However, since there was no clinical improvement for P3 over the first year and her T-IgE increase to 19,239UI/ml and SCORAD to 40, the SIT was stopped. CONCLUSIONS:Wehave observed a rapid onset of action after initiation of SIT in some cases of Severe AD. Clinical improvement was correlated with the decrease in T-IgE. The SIT may be a therapeutic alternative.

A Randomized, Open-Label, Parallel Group Study to Evaluate the Efficacy and Safety of Proactive Management in Pediatric Subjects with Moderate to Severe Atopic Dermatitis

S U N D A Y 366 Allergen Specific Immunotherapy in Cases of Severe Atopic Dermatitis Inmaculada S anchez-Mach in, MD, Paloma Poza, Ruperto Gonz alez, Victor Matheu, MD; Hospital Ofra-T orax, Tenerife, Spain, Hospital Ofra-T orax, santa cruz de tenerife, Spain, Hospital Ofra-T orax, S/C de Tenerife, Spain, Hospital Ofra, Tenerife, Spain. RATIONALE: Allergen sensitization appears to be part of the etiology of Atopic Dermatitis (AD). The effectiveness of allergen specific immunotherapy (SIT) in AD remains controversial, even contraindicated in severe cases. METHODS: Total IgE (T-IgE) and Specific IgE (S-IgE) by CAPFarmacia. Patient 1 (P1): 43-year-old male. Patient 2 (P2): 31-year old woman. Patient 3 (P3): 9-year-old woman. All of them were nonresponders to usual therapeutics including corticosteroids oral (Last year daily for P1, P2, and 6 cycles for P3), cyclosporin (P1, P2) or methotrexate (P1with bloody diarrhea). They hadmild persistent rhinitis and intermitent asthma and positive S-IgE to Dermatophagoidesand storage mites, and P1 also to grass, ragweed pollen and foods without clinical relevance. RESULTS: In a first visit SCORAD and T-IgEwere: P1, 81 and 31,090UI/ ml. P2, 75 and 19,038UI/ml. P3, 36 and 14.897UI/ml.We started treatment with SIT, with cluster administration schedule of 4weeks in Hospital Immunotherapy Unit and subsequent monthly maintenance. The early months P1 and P2 showed improvement. The T-IgE was descending in improved patients to be in the 4 year of SIT: 5,560UI/ml for P1 and 2,500UI/ml for P2 with SCORAD of 11 and 5 respectively. However, since there was no clinical improvement for P3 over the first year and her T-IgE increase to 19,239UI/ml and SCORAD to 40, the SIT was stopped. CONCLUSIONS:Wehave observed a rapid onset of action after initiation of SIT in some cases of Severe AD. Clinical improvement was correlated with the decrease in T-IgE. The SIT may be a therapeutic alternative.

Birch pollen immunotherapy results in long-term loss of Bet v 1–specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies

Early events of specific immunotherapy (SIT) are induction of allergen-specific IL-10-producing T(R)1 cells and production of IgG antibodies, but there is little knowledge about the long-term immune mechanisms responsible for sustained allergen tolerance. Bet v 1-specific immune responses of 16 patients with birch pollen allergy were characterized up to 54 months at defined time points before, during, and after a 3-year period of SIT. We sought to analyze allergen-specific T- and B-cell responses. Bet v 1-specific IL-5-, IFN-γ-, and IL-10-secreting T cells were quantified in peripheral blood, and birch pollen-specific IgE and IgG antibody levels were determined in serum. Furthermore, the inhibitory capacity of SIT-induced IgG was evaluated by blocking allergen binding to IgE and inhibition of facilitated allergen presentation. Seasonal increases in Bet v 1-specific T(H)2 cell numbers ceased to appear after the first year of SIT without deviation to a T(H)1-dominated immune response. Furthermore, the frequency of IL-10-producing T(R)1 cells, which had increased during the first year of SIT, returned to pretreatment levels in the second year. In contrast, allergen-specific IgG antibody concentrations continuously increased during SIT but started to decrease after cessation of treatment. Functional analysis confirmed the ability of the IgG antibodies to inhibit IgE-allergen interactions, which peaked at the end of SIT but then slowly started to decrease. Long-term allergen tolerance achieved by SIT is associated with the development of peripheral T-cell tolerance characterized by decreased reactivity of Bet v 1-specific T(H)2 cells and enriched allergen-specific IgG competing with IgE antibodies for allergen binding.

Comparison of the long-term efficacy of 3- and 5-year house dust mite allergen immunotherapy

BackgroundThe recommended duration of specific immunotherapy (SIT) treatment relies on empiric data and is not well documented. ObjectiveTo detect possible differences in the long-term effectiveness between 3 and 5 years of house dust mite (HDM) SIT in asthmatic children. MethodsWe performed a 3-year natural history study of 90 asthmatic children who were sensitive only to HDM. Three groups were recruited: 30 who had completed 3 years of HDM SIT (SIT3), 30 who had completed 5 years of HDM SIT (SIT5), and 30 who had an indication for HDM SIT but whose parents refused HDM SIT. Patients attended an enrollment visit in 2007, after SIT discontinuation, and 3 annual follow-up visits at the clinic. The long-term effectiveness of HDM SIT was primarily assessed via analysis of the reduction in required inhaled corticosteroid dose, forced expiratory volume in 1 second, and asthma remission. ResultsA total of 84 children completed the study. Both SIT durations produced excellent results; asthma remission in both SIT3 (50%) and SIT5 (54%) groups was significantly higher when compared with control (3.3%). The minimal controlling inhaled corticosteroid dose reduction in SIT5 group (median, 75%) was significantly higher compared with the SIT3 group (median, 50%) after immunotherapy discontinuation; after 3 years without SIT, no differences were found between the SIT5 and SIT3 groups (median, 100% and 94%, respectively). We observed a slightly higher increase in forced expiratory volume in 1 second in the SIT5 group compared with the SIT3 group. ConclusionThree years of SIT is an adequate duration for the treatment of childhood asthma associated with HDM allergy because 2 further years of SIT added no clinical benefit.

488 The Effect of Specific Immunotherapy on the Clinical Response in Patients with Grass-pollen Induced Rhinoconjunctivitis

BackgroundSpecific immunotherapy (SIT) has a significant potential in the treatment of allergic rhinitis and allergic conjunctivitis. The aim of the study was to evaluate the effect of specific immunotherapy (SIT) in patients with grass-pollen induced allergic rhinitis and allergic conjunctivitis.MethodsTwenty-six patients with pollen induced rhinoconjunctivitis and positive history for more than 2 years were included in our study. They had skin prick test of ≥ 5 mm, age range from 18 to 44 years and all underwent conjunctiva provocation tests before and after 1 year of SIT. Clinical severity score of nasal and conjunctiva symptoms during the season was assessed by 4-point arbitrary rating scale from 0 to 3. Conjunctiva provocations were performed out of the season until allergic symptoms occurred, achieving the allergen threshold dose (ATD).ResultsAfter 1 year of SIT, we have noticed reduction of clinical symptoms present in allergic conjunctivitis: burning, itching, lacrimation and hyperemia (P < 0,05). We have found also reduction in clinical symptoms of allergic rhinitis: secretion, irritation, itching and nasal blockade (P < 0,01). The patients tolerated significantly higher allergen doses in provocation tests after 1 year of SIT, reaching new ATD.ConclusionsSIT reduces the clinical symptoms of allergic rhinoconjunctivitis and modifies the inflammatory response after specific allergen challenge.

Three years of specific immunotherapy may be sufficient in house dust mite respiratory allergy

Specific immunotherapy (SIT) duration for respiratory allergy is currently based on individual decisions. To evaluate the differences in clinical efficacy of SIT as a result of the duration between the current recommended limits (3-5 years). A 5-year prospective, controlled clinical trial of SIT blind until the first year and randomization to a 3-year (IT3) or 5-year (IT5) course was conducted. Of the 239 patients with respiratory allergy caused by D pteronyssinus initially included, 142 completed 3 years of SIT with good compliance. Twenty-seven controls were included at the third year. Efficacy of SIT after 3 (T3) and 5 (T5) years was assessed by using clinical scores, visual analog scales (VASs), rhinitis (RQLQ) and asthma (AQLQ) quality of life questionnaires, skin tests, and serum immunoglobulins. At T3, significant reductions were observed in rhinitis (44% in IT3 and 50% in IT5; P < .001), asthma (80.9 % in IT3 and 70.9% in IT5; P < .001) scores, VAS (P < .001 in both), RQLQ (P < .001 in both) and AQLQ (P < .001 in both). At T5, the clinical benefit was maintained in both groups, and IT5 patients presented additional decreases (19%; P = .019) in rhinitis scores. At Tf, specific IgG(4) measurements were lower in IT3 (P = .03) without detecting differences in IT5. An increase in asthma score of 133% was the only difference observed in controls. Clinical improvement is obtained with 3 years of D pteronyssinus SIT. Two additional years of SIT add clinical benefit in rhinitis only.

Preventing progression of allergic rhinitis: the role of specific immunotherapy

Allergic rhinitis and asthma are examples of allergic airways disease. Despite their differing symptomatology, both disorders affect the mucosal lining of the respiratory tract and are linked by common underlying...

Three Years of Specific Immunotherapy may be enough to treat respiratory allergy

Three Years of Specific Immunotherapy may be enough to treat respiratory allergy

Five‐year follow‐up on the PAT study: specific immunotherapy and long‐term prevention of asthma in children

A 3-year course of specific immunotherapy (SIT) in children with hay fever to grass and/or birch pollen significantly reduced the risk of developing asthma. To investigate the long-term preventive effect, we performed a follow up--2 years after termination of immunotherapy. A total of 183 children, aged 6-14 years with grass and/or birch pollen allergy could be investigated 2 years after discontinuation of SIT or no treatment. Conjunctival provocation tests (CPTs) and methacholine bronchial provocation tests were carried out during the season and winter after 5 years. The development of asthma was assessed by clinical evaluation. The significant improvement in hay fever and CPT results observed after 3 years of SIT persisted at the 5-year follow-up. No difference in bronchial responsiveness to methacholine was found after 5 years because of spontaneous improvement during the follow-up period in the control patients. The immunotherapy-treated children had significantly less asthma after 5 years as evaluated by clinical symptoms [odds ratio 2.68 (1.3-5.7)] in favor of SIT for prevention of development of asthma and significantly less patients reported an increase in asthma scores (P < 0.01). Immunotherapy for 3 years with standardized allergen extracts of grass and/or birch shows long-term clinical effect and preventive effect on development of asthma in children with seasonal rhinoconjunctivitis.

Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi‐centre, randomized, dose–response study

The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose-response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD >or=40 and allergic sensitization to house dust mites [CAP-FEIA >or=3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2,000 and 20,000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere-Terpstra test) and was significantly lower in the two high-dose groups (2,000, 20,000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel-Haenszel chi-square test). Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.

Efficacy of Injection Immunotherapy with Ragweed and Birch Pollen in Elderly Patients

Background: The role of specific immunotherapy (SIT) in elderly allergic patients is still debated. Objective: The aim of this study was to assess whether SIT is associated with a better control of symptoms and a better quality of life also in older allergic patients. Methods: The effect of injection SIT was assessed in 39 patients [age >54 years, median 59; 29 patients (74%) with asthma, otherwise healthy] monosensitized to birch (n = 20) and ragweed (n = 19). Thirty-three younger subjects [age <50 years, median 35; 26 patients (79%) with asthma, otherwise healthy] monosensitized to birch (n = 10) and ragweed (n = 23), and 37 subjects >54 years old (25 males/12 females; age 55–79 years, median 59 years) monosensitized to birch (n = 18) and ragweed (n = 19) who refused to undergo SIT were enrolled as positive and negative controls, respectively. All groups had a disease duration <10 years; the disease was inadequately controlled with standard drug therapies in all cases. SIT was carried out using the same extracts and was administered using a perennial schedule both in patients and controls. Seasonal therapies were the same in all groups and were not changed after SIT was started. After 1–5 years of SIT, patients and controls were asked to quantify symptom reduction on a visual analogue scale: reductions >50% were considered significant. Moreover, the use of cetirizine and/or salbutamol as an adjunct to standard therapies during the last pollen season was assessed as an objective measure of SIT outcome. Results: 37/39 (95%) patients versus 32/33 (97%) controls submitted to SIT reported a symptom reduction >50% after 1–5 years of SIT (nonsignificant). The median clinical efficacy of SIT was 80% in both groups (nonsignificant). 27/37 controls not submitted to SIT did not report any change in symptom severity at the follow-up visits, whereas 10/37 reported a more severe disease (4 subjects reported the appearance of seasonal asthma) (p < 0.001 vs. patients submitted to SIT). Patients used less frequently cetirizine (p < 0.001) and/or salbutamol (p < 0.05) than controls not submitted to SIT. Conclusion: Injection SIT can be considered an effective therapeutic option in otherwise healthy elderly patients with a short disease duration whose symptoms cannot be adequately controlled by drug therapies alone.

Adhesion molecules and efficacy of specific immunotherapy

Rationale Adhesion molecules evaluation may be used as an inflammation marker in allergy and to evaluate specific immunotherapy (SIT) efficacy. We evaluated the evolution of ICAM-1 and VCAM-1 in their soluble and cellular forms during SIT in patients allergic to house dust mite ( Dermatophagoides pteronyssinus-D.pter.). Methods 3 groups of patients with allergic rhinitis confirmed by clinically history, skin tests and specific IgE (sIgE). Group I: 20 patients (15-55 years old), 8 females, 12 males with SIT, performed with a modified extract of D.pter, Depigoid®. Group II: 20 patients (15-55 years old) 8 females, 12 males, with SIT modified to 1/10 of the concentration. Control group: 15 patients (15-55 years old), 7 females, 8 males, with respiratory allergy without SIT. Serum levels of ICAM-1 and VCAM-1: ELISA R&D. Cellular adhesion molecules: flow cytometry (FACSCalibur) CD54, CD106. Blood collected in all patients before SIT (T0), after 6 months (T1), after 1 year (T2). Results Group I: mean serum level of ICAM-1: T0-372,6ng/ml; T1-324,3ng/ml; T2-265,31ng/ml (p<0.001); VCAM-1: T0-677,36ng/ml; T1-605.09ng/ml; T2-523,76ng/ml (p=0.001). Mean of % for CD54: T0-20,84; T1-23,72; T2-27,48 (p=0.04). Group II: ICAM-1: T0- 370.5ng/ml; T1-308,4ng/ml; T2-209,5ng/ml (p<0.001). VCAM-1: T0-672,4ng/ml; T1-602.9ng/ml; T2-503,56ng/ml (p=0.002). CD54: T0-23,96; T1-27,76, T2-27,52 (p=0.102). Control group: ICAM-1: T0-363,16ng/ml; T1-350,41ng/ml; T2-376,5ng/ml (p=0.303), VCAM-1: T0-671,58ng/ml; T1-640.43ng/ml; T2-678,5ng/ml (p=0.412); CD54: T0-16,12; T1-21,04; T2-22,40 (p=0.06). CD106 negative in all groups. Conclusions After 1 year of SIT, there is a significant decrease of the serum levels of ICAM-1 and VCAM-1, supporting SIT efficacy. Mean values of CD54 in the 3 groups showed a slight increase especially in group 1. sICAM-1 and sVCAM-1 seems to be useful markers of inflammation during SIT.

Effect of specific immunotherapy with house dust mite extract on the bronchial responsiveness of paediatric asthma patients.

Allergic asthma is common in children, and house dust mite (HDM) is an important source of perennial allergens. Bronchial hyperresponsiveness is a functional hallmark of asthma. Specific immunotherapy (SIT) with HDM extracts were shown to decrease symptoms, but its effect on bronchial responsiveness, as measured by non-pharmacological challenges, has not been evaluated. Twenty-six paediatric asthma patients allergic to HDM participated in this study. Fourteen patients received SIT with a HDM extract (Alavac, Bencard) for 2 years, and 12 served as controls. Bronchial responsiveness was assessed non-pharmacologically by cold dry air challenge (CACh) before and 3, 6, 12 and 24 months after SIT, and 12 months after termination of SIT. After 24 months, the SIT group showed a statistically significant reduction of the mean CACh-induced changes of both forced expiratory volume in one second (-21.8+/-2.7% vs. -13.7+/-2.4%; P = 0.03) and maximal expiratory flow at 25% remaining vital capacity (-48.9+/-4.9% vs. -27.9+/-6.2%; P = 0.01). In contrast, no significant changes of bronchial responsiveness were observed in the control group. In the SIT group more patients lost their bronchial hyperresponsiveness than in the control group (6/14 vs. 1/12; P<0.05). One year after terminating SIT, the treatment group showed a tendency towards returning bronchial hyperresponsiveness. These results demonstrate that during 2 years of SIT there was a reduction of bronchial hyperresponsiveness in HDM-allergic paediatric asthma patients.

Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T‐cell clones specific for Phi p 1, a major grass pollen allergen

The mechanisms operative in specific immunotherapy (SIT) of Type I allergy are not completely understood. In the present study we evaluated immunological changes during SIT in pollinosis. Eight patients suffering from pollinosis (monosensitized to grass pollen) were treated with conventional SIT. All subjects had IgE specific for Phl p 1, a major allergen of timothy grass. In vitro changes in the immunological reactivity to grass pollen extract and to recombinant Phl p 1 were evaluated. Subjects were examined at three occasions: before, after 3 months and after 1 year of SIT. Serological analysis revealed a marked increase of grass pollen- and Phl p 1-specific IgG, titres of specific IgE did not change significantly. Lymphoproliferative responses to grass pollen extract and rPhl p 1 were reduced already after 3 months of treatment. Accordingly, the cloning efficiency for Phl p 1-specific T-cell clones (TCC) dropped markedly in all patients. The majority of allergen-specific TCC raised before SIT revealed a TH2-like pattern of cytokine production, TCC established after SIT revealed TH1 characteristics. This shift was due to a decrease in IL-4 rather than an increase in IFN-production by T cells. Investigations of the epitopes recognized by T cells before and after SIT did not reveal the outgrowth of new ('protecting') specificities. We could not observe induction of allergen-specific CD8+ lymphocytes (supressor cells). Our data indicate that -- on the level of TH lymphocytes -- SIT induces tolerance to the allergen and a modulation of the cytokine pattern produced in response to allergen stimulation.

378 Efficacy of one year of specific immunotherapy (SIT) with an alginate conjugated parietaria officinalis (PO) extract in parietaria allergic rhinitis

378 Efficacy of one year of specific immunotherapy (SIT) with an alginate conjugated parietaria officinalis (PO) extract in parietaria allergic rhinitis