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PubMed2001

Sublingual tryptase and ECP in children treated with grass pollen sublingual immunotherapy (SLIT): safety and immunologic implications.

BACKGROUND: The clinical safety of sublingual immunotherapy (SLIT) has been repeatedly confirmed; nevertheless, the possible onset of local oral symptoms is still a concern, and nothing is known about the pathogenesis of this effect. We aimed to determine whether the administration of SLIT in allergic children can evoke an IgE-mediated reaction, by measuring the levels of sublingual tryptase and ECP. METHODS: Thirty children (7-12 years old) with allergic rhinitis/asthma due to grass pollen were prescribed SLIT. In these children, an allergen-specific nasal challenge was performed, and nasal tryptase and ECP were measured before and after. Sublingual ECP and tryptase were also assessed before the SLIT, after 1 month, and after 6 months of treatment. Ten matched allergic children and 10 healthy ones served as controls for the baseline levels of sublingual ECP and tryptase. RESULTS: The levels of nasal tryptase and ECP significantly increased after nasal challenge (P<0.001), whereas no change during the SLIT course (at the beginning, after 1 month, and after 6 months) could be detected in sublingual tryptase either before or after SLIT administration. The sublingual ECP significantly decreased after 6 months of SLIT. The baseline levels of nasal tryptase and ECP were significantly higher in allergic subjects than in healthy controls, as was the level of sublingual ECP. CONCLUSIONS: In the presence of an IgE-mediated reaction (ASNC), a significant increase of tryptase and ECP can be seen. When SLIT is administered, such a phenomenon does not occur; therefore, SLIT does not elicit any IgE reaction in the mouth. It is noteworthy that allergic subjects display higher levels of nasal ECP and tryptase than healthy subjects, even when symptom-free, and these observations may indicate the presence of subclinical inflammation.

Administration, Sublingual↗

PubMed2002

Similar T helper Th2-like cytokine mRNA expression in vernal keratoconjunctivitis regardless of atopic constitution.

BACKGROUND: Many patients with vernal keratoconjunctivitis (VKC), a severe chronic allergic eye disease in children, exhibit IgE-sensitization, but about 40% of cases lack this immunologic trait. As a disease factor in VKC, IgE is thus not fully understood. The aim of this study was to investigate whether there are any differences in the conjunctival cytokine messenger (m)RNA pattern related to IgE-sensitization in children suffering from VKC. METHODS: Tissue samples were obtained from 16 symptomatic VKC subjects with sub-tarsal disease and six control subjects. Expression of mRNA for interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-gamma was investigated with a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) technique. The presence of T cells, IgE+ cells, mast cells, and eosinophils was analyzed with immunohistochemical methods. Allergen-specific IgE antibodies were assessed in serum and with skin prick testing. RESULTS: Ten out of the 16 VKC subjects showed evidence of IgE-sensitization. No differences were detected for any tissue variable between VKC subjects with and without IgE-sensitization. Statistically significant increases over controls were found for both VKC groups with regard to all cell markers. CONCLUSIONS: The amount of messenger RNA encoding cytokines and inflammatory cell markers in VKC did not correlate with IgE-sensitization. Tissue changes in all patient samples were characterized by a prevalence of T cells, eosinophils, mast cells and cell-bound IgE molecules. However, the role of cell-bound IgE molecules in VKC patients lacking IgE-sensitization remains to be determined.

Adolescent↗

PubMed2001

New insight into immunological mechanisms of venom immunotherapy.

The early production of IL-10 appears to induce T cell anergy and is an important step in venom immunotherapy. This results in the loss of the abnormal venom-specific T helper type 2 response (reduced proliferation and cytokine production) and a switch from a T helper type 2 dominant to a T helper type 1 dominant cytokine response. As a consequence, there is an increase in specific IgG4, an increase in the specific IgG4:IgE ratio, and over the longer term a decrease in specific IgE. IL-10 is initially produced by allergen-specific T cells, but later by B cells and monocytes. IL-10 initiates anergy in T cells by blocking tyrosine phosphorylation of CD28 and inhibiting the CD28 co-stimulatory signal. IL-10 also inhibits cytokine gene transcription and messenger RNA production. That clinical protection in venom immunotherapy occurs earlier than antibody changes suggests that additional mechanisms may be operative. Decreased basophil mediator release is a candidate and has been demonstrated: it is induced by IL-10 and possibly also related to changes in chemokines and other cytokines. Proliferation and cytokine secretion in anergic T cells can be restored depending on the cytokine milieu. Restimulation in the presence of IL-2, IL-15 and possibly IL-12 leads to a T helper type 1 cytokine pattern (immunity:effective immunotherapy) and with IL-4 a T helper type 2 pattern (persistence of allergy:relapse). The cytokine microenvironment in tissues can thus influence outcome. A variety of new approaches to immunotherapy is being investigated, including peptide therapy. Preliminary data from DNA vaccines, largely in animal models, hold great promise. Immunostimulatory DNA sequences have an adjuvant effect and induce T helper type 1 cytokines, independent of antigen. They may be co-administered with allergen and used to redirect allergen-specific T helper type 2 responses.

Allergens↗

PubMedDate not supplied

Efficacy, safety, and modulation of immunologic markers by immunotherapy with honeybee venom: comparison of standardized quality depot versus aqueous extract.

Venom immunotherapy (IT) is a very effective method for the treatment of Hymenoptera venom allergy. We compared safety, efficacy, and modulation of specific immunologic parameters in 70 patients sensitized to Apis mellifera, treated for > or = 5 years with standardized quality (SQ) aqueous IT, either with a rush (n = 20) or with a cluster (n = 20) induction protocol, or with an SQ depot extract and a cluster induction protocol (n = 30). We made an open, noncontrolled study. Side effects were monitored and the effects of field stings during the maintenance phase of the treatment and after its interruption were recorded. Skin reactivity to Apis was measured by end point dilution and specific serum immunoglobulin E (IgE) were measured by a solid-phase-based assay. The depot IT was better tolerated than aqueous IT with rush induction. This was caused by mainly the lower frequency in the induction phase of systemic side effects (3.4% versus 36.8% [p < 0.0041] on a "per patient" and 0.1% versus 0.9% [p = 0.0092] on a "per dose "basis, respectively). The cluster protocol with the aqueous extract tended to be better tolerated that the rush protocol. About one-half of patients from each group were re-stung during the study and all suffered only minor discomfort. Reduction of skin reactivity and of serum-specific IgE was significant in the three groups (p < 0.02 in all cases). SQ Depot IT to Apis venom allergy administered with a cluster protocol induces less side effects and is equally effective then IT with SQ aqueous extract administered with a rush protocol.

Adolescent↗

PubMed2006

Insect sting allergy and venom immunotherapy.

OBJECTIVE: To review specific aspects of venom immunotherapy (VIT) in the context of allergen immunotherapy (AIT) in general. DATA SOURCES: Immunotherapy Collegium II presented at the 2005 Annual Meeting of the American College of Allergy, Asthma and Immunology. STUDY SELECTION: Discussions of VIT during Immunotherapy Collegium II. RESULTS: The decision to recommend VIT is based on a detailed history and confirmatory diagnostic tests, as well as a knowledge of the natural history of the disease and its impact on quality of life. Skin tests and radioallergosorbent tests are complementary in that neither can detect all cases of insect sting allergy. Unlike inhalant AIT, rush regimens are as safe as slower regimens for initial VIT, and 4- to 8-week maintenance intervals are typical for VIT. In contrast to inhalant AIT, large local reactions are common and expected with VIT and should not limit the maintenance dose. VIT induces full immune tolerance in 85% of patients after 5 years, whereas this occurs in 30% to 50% of patients with inhalant AIT. VIT is often discontinued after 5 years even though skin test results are usually still positive, but a 10% to 15% chance of reaction persists for many years and is greater in patients who had near-fatal reactions before treatment, those who had systemic reactions during VIT, those with honeybee allergy, and those treated for less than 5 years. Children who receive 3 to 5 years of VIT have a lasting immune tolerance for 10 to 20 years afterward. CONCLUSION: The appropriate use of VIT for prevention of insect sting allergy requires knowledge of the natural history of the disease and would benefit from a better understanding of the mechanisms of successful immunotherapy for the induction of immune tolerance.

Bites and Stings↗

PubMedDate not supplied

Immunological properties of allergen chemically modified with synthetic copolymer of N-vinylpyrrolidone and maleic anhydride.

Several conjugates of model allergen ovalbumin (OA) and the copolymer of N-vinyl pyrrolidone and maleic anhydride (VMA) modified with epsilon-aminocaproic acid (Acp) were prepared in different OA/Acp-VMA ratios. All conjugates were separated by ultrafiltration and analyzed by HPLC. Their compositions were determined by amino acid analysis and UV spectrometry. To detect immunogenicity, all conjugates were injected intraperitoneally into (CBAxC57BL/6)F1 mice three times in 3-week intervals in OA doses equivalent to 0.5, 10, and 100 micrograms/mouse. Only the conjugate containing 20%OA (OA(20%)-Acp-VMA) did not induce significant quantities of anti-OA IgE, but did induce anti-OA IgG antibodies in dose-dependent manner comparable to that of unmodified OA. Mixtures of OA and Acp-VMA or OA modified only with VMA without Acp activation with Acp induced dose-dependent anti-OA IgE and IgG antibody formation comparable to that of OA. Using passive cutaneous anaphylaxis, RAST inhibition and leukocyte histamine release, a significant reduction of allergenicity was noted using OA(20%)-Acp-VMA. This conjugate stimulated activation of the OA-specific T-cell hybrid 3DO-548 comparable to that of unconjugated OA. During experimental allergen-specific hyposensitization with OA(20%)-Acp-VMA, suppression of anti-OA IgE response and elevation of anti-OA IgG responses were noted when compared with unmodified OA. Selective blockade of B-cell epitopes of allergen may occur using the carrier Acp-VMA to reduce allergenicity while not affecting T-cell epitopes, thereby preserving immunogenicity. This approach of chemical modification of allergen suggests new opportunities in the creation of preparations for allergen-specific immunotherapy.

Allergens↗

PubMed1984

Immunologic responses to conjugates of antigen E in patients with ragweed hay fever.

Allergens conjugated with several simple repeating polymers have reduced allergenicity in man, but large doses retain the ability to suppress ongoing allergen-specific IgE synthesis in strains of high-responder mice. To determine whether suppression of IgE antibodies could be induced in man, preliminary trials of immunologic responses to conjugates in man were carried out in ragweed hay fever patients treated with antigen E (AgE) coupled to methoxypolyethylene glycols ( MPEGs ) of 5000 and 2000 daltons, lauryloxypolyethylene glycol of 1200 daltons, and a random copolymer of D-lysine and D-glutamic acid of 69,000 daltons. In varying degrees all these conjugates had reduced allergenicity by basophil histamine release when these conjugates were compared with native AgE and could suppress IgE response in mice. Patients received one of these conjugates or native AgE in a series of subcutaneous injections and were observed for allergic reactions. The conjugates induced a lower rate of systemic reaction than native AgE but failed to induce early suppression of IgE antibodies. Instead, early rises in IgE antibody occurred in the several groups and were followed by a slow decline during a year or more that was similar to that observed with standard immunotherapy. Because the conjugates eventually caused local and systemic allergic reactions as the dose was raised, it was not possible to test the IgE-suppressive effects at doses similar to those used in mice. In contrast, rapid sustained rises in IgG antibodies occurred in all groups. The MPEG conjugates appeared to be more effective than native AgE in this regard. The reduced rate of systemic reaction and rapid rise in IgG antibody that was noted with MPEG conjugates make them worth further exploration as agents for immunotherapy.

Allergens↗

PubMed1998

Molecular and immunologic characterization of a highly cross-reactive two EF-hand calcium-binding alder pollen allergen, Aln g 4: structural basis for calcium-modulated IgE recognition.

Serum IgE was used to isolate a cDNA coding for a 9.4-kDa two EF-hand calcium-binding allergen, Aln g 4, from a lambda gt11 expression cDNA library constructed from alder (Alnus glutinosa) pollen. rAln g 4 was overexpressed in Escherichia coli and purified to homogeneity. It reacted with serum IgE from 18% of pollen-allergic patients (n = 122); shared IgE epitopes with homologous allergens present in tree, grass, and weed pollens; and thus belongs to a family of highly cross-reactive pollen allergens. Exposure of two E. coli-expressed rAln g 4 fragments comprising amino acids 1-41 and 42-85 to patients' IgE Abs, as well as to a rabbit antiserum raised against purified rAln g 4, indicated that most of the B cell epitopes reside in the N-terminal portion of the protein. IgE recognition of Aln g 4 was strongly modulated by the presence or absence of calcium. Circular dichroism analysis of rAln g 4 revealed that the protein consisted mostly of alpha helical secondary structure and possessed a remarkable thermal stability and refolding capacity, a property that was greatly reduced after calcium depletion. Circular dichroism analysis of the calcium-bound and apo form of rAln g 4 indicated that calcium-induced modulation of IgE binding could be due to changes in the protein conformation. Purified rAln g 4 elicited dose-dependent basophil histamine release and immediate type skin reactions in sensitized patients. It may hence be useful for allergy diagnosis and for specific immunotherapy.

Allergens↗

PubMed1998

Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma.

In the present study, we investigated whether allergen immunotherapy is effective in a murine model with immunologic and pathophysiologic features reminiscent of allergic asthma. Ovalbumin-sensitized mice received increasing (1 microgram to 1 mg) subcutaneous doses of ovalbumin twice a week for 8 wk according to a semirush immunotherapy protocol as used in allergic patients. During immunotherapy, an initial rise in serum levels of ovalbumin-specific antibodies (immunoglobulin [Ig]G1, IgE, IgG2a) occurred, after which IgE levels decreased sharply concomitant with an increase in IgG2a levels. The increase in IgG2a levels, with the decline in IgE levels, suggests that during immunotherapy interferon-gamma production is increased or interleukin (IL)-4 production is decreased. After immunotherapy, inhalation challenge of the mice with ovalbumin revealed almost complete inhibition (98%, P < 0.01) of eosinophil infiltration into bronchoalveolar lavage and airway hyperresponsiveness (100% at 320 microgram/kg methacholine, P < 0.05) compared with sham-treated animals. In addition, IL-4 production of thoracic lymph node cells stimulated with ovalbumin in vitro was largely reduced (60%, P < 0.05) after immunotherapy. Thus, effective immunotherapy in this animal model appears to be due to modulation of antigen-specific T cells. Similar effects on airway symptoms and IL-4 production can be obtained within 1 wk by three injections of the highest dose of ovalbumin (1 mg). This animal model will be used as a preclinical model to improve allergen immunotherapy and to gain more insight into the mechanisms involved.

Alveolitis, Extrinsic Allergic↗

PubMed1998

Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization.

For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose, 66 children with seasonal asthma, rhinitis, and conjunctivitis due to sensitization to olive pollen were enrolled in a double-blind, randomized, placebo-controlled study between October 1994 and October 1996 in Greece. Thirty-four patients were randomly allocated to the active group, and 32 received placebo. Immunotherapy consisted of olive-allergen extracts (Stallergènes SA) administered sublingually pre- and coseasonally from January to July for 2 consecutive years. Serial concentrations from 1 to 300 IR. were used up to the maintenance dose of 20 drops of 300 IR daily. The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy, and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years. The patients were assessed by clinical parameters (symptom and medication scores from patients' daily diaries) and immunologic measurements (specific IgE, IgG4, eosinophil cationic protein [ECP]) were performed. The actively treated patients had a significantly lower score for dyspnea (P<0.04 during the first season; P<0.03 during the second season). At the pollinic peak during the second year, a lower score of conjunctivitis was recorded (P<0.05) in the actively treated patients. The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo, whereas there was no symptomatic peak for the same period in the group under active treatment. However, the difference between the groups was not significant. The medication score did not differ significantly between the groups. Oral steroids were the only variables with a P value near the significance level (P=0.06) in favor of the actively treated group. A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment. No significant variation in specific IgE and IgG4 was detected. A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season (P=0.01), but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings. Tolerance was excellent with only a few minor side-effects reported. In conclusion, high-dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive-pollen sensitization.

Administration, Sublingual↗

PubMed2001

Allergen-specific sublingual immunotherapy for respiratory allergy.

Present knowledge regarding the clinical efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of respiratory allergy is reviewed. Allergen-specific immunotherapy is presently considered a 'biological response modifier' for the treatment of respiratory allergy, to be used in association with drug therapy and allergen avoidance. Its value in the treatment of these conditions has been established in position papers from the World Health Organization and the European Academy of Allergology and Clinical Immunology. Immunotherapy is usually administered subcutaneously (SCIT), and with this route several severe adverse events and fatalities have been described. Therefore, in the last 15 years, novel and safer routes of administration (local routes) have been developed. SLIT, in particular, has been investigated in 18 randomised controlled clinical trials. SLIT's clinical efficacy (improvement in symptoms and reduction in drug intake) in both asthma and rhinitis has been clearly assessed in 16 of these studies and for the most common allergens. SLIT's safety profile, derived from the clinical trials and from post-marketing surveillance studies, was shown to be satisfactory in both adults and children. The most frequently reported adverse events are gastrointestinal complaints, which can be avoided through appropriate dosage adjustment. For these reasons, SLIT has been accepted as a viable alternative to SCIT in recent position papers. The main advantages of SLIT are its safety (no severe systemic adverse event has ever been described) and good patient acceptance, especially in children; in addition, SLIT is a self-administered treatment that can be carried out at home by the patient. In contrast to injection immunotherapy, knowledge of the mechanisms of action of SLIT is still developing, albeit rapidly, although interesting data about its pharmacokinetics in humans are available. Data are also required concerning the possible preventive and long-lasting effects. SLIT is a viable alternative to SCIT, with the same rationale and indications. It is intended to be used in association with proper pharmacological treatment, at the earliest stages of the disease, for optimal management of respiratory allergy.

Administration, Sublingual↗

PubMed1998

Bee sting allergy in beekeepers.

BACKGROUND: Beekeepers are strongly exposed to honey bee stings and therefore at an increased risk to develop IgE-mediated allergy to bee venom. OBJECTIVE: We wondered whether bee venom-allergic beekeepers were different from normally exposed bee venom-allergic patients with regard to clinical and immunological parameters as well as their response to venom immunotherapy. METHOD: Among the 459 bee venom-allergic patients seen over the 5 year period 1987-91, 62 (14%) were beekeepers and 44 (10%) family members of beekeepers. These two groups were compared with 101 normally exposed bee venom-allergic patients matched with the allergic beekeepers for age and sex, regarding clinical parameters, skin sensitivity, specific IgE and IgG antibodies to bee venom as well as safety and efficacy of venom immunotherapy. RESULTS: As expected, allergic beekeepers had been stung most frequently before the first allergic reaction. The three groups showed a similar severity of allergic symptoms following bee stings and had an equal incidence of atopic diseases. Allergic beekeepers showed higher levels of bee venom-specific serum IgG, lower skin sensitivity and lower levels of bee venom specific serum IgE than bee venom-allergic control patients. A negative correlation between number of stings and skin sensitivity as well as specific IgE was found in allergic beekeepers and their family members, while the number of stings was positively correlated with specific IgG in these two groups. Venom immunotherapy was equally effective in the three groups, but better tolerated by allergic beekeepers than the two other groups. The majority of allergic beekeepers continued bee-keeping successfully under the protection of venom immunotherapy. CONCLUSION: The lower level of sensitivity in diagnostic tests and the better tolerance of immunotherapy in allergic beekeepers is most likely related to the high level of specific IgG in this group.

Adult↗

PubMedDate not supplied

Oral tolerance in the control of experimental models of autoimmune disease.

Autoimmune inflammatory diseases, including many human arthritides, cause significant morbidity and mortality. The control of their immunological aspects is central to management of the diseases and usually involves drugs that are, in the immunological sense, non-specific in their effects. The efficacy of such drugs may be limited, and they may have side-effects so serious that if immunologically specific means were available to control these diseases, there would be significant benefits. Immunological specificity is carried only by antibodies, T cell receptors, MHC molecules and, of course, antigen. Based upon the experimental outcome of inducing systemic specific immunological unresponsiveness-the so-called oral tolerance effect-by feeding antigens, several groups have investigated the effects on experimental autoimmune diseases of delivering autoantigens across gastric and respiratory mucosal surfaces. Three forms of arthritis, those induced by type II collagen, adjuvant and oil, respectively, have been examined in this way, and the results from these studies show that disease can be specifically prevented or ameliorated. In parallel, examination of experimental encephalitis and uveitis, as examples of neurological diseases, and diabetes in the NOD mouse, have produced the same results. This review discusses the results of these experimental studies and draws out their common features. The uniform finding is that T cells are made hyporesponsive, and that the most likely mechanism is one of active suppression mediated through the selective activation of T cells, of either CD4+ or CD8+ phenotype, that make cytokines which in turn can suppress pathological T cells responsible for the disease lesions. There are many unanswered questions concerning optimal dosage regimes, routes and vehicles for antigen delivery and antigen pharmacokinetics that need to be answered if the promising results of early human trials are to be exploited with benefit. At the fundamental level, the full identity of the cell type, or types, responsible for the tolerance, most likely to be active peripheral suppression, is still elusive. Given the complexity of disease processes in the different situations that have been examined, it is likely that no one mechanism applies in all, and that therefore different therapeutic approaches will need to be tailored accordingly.

Administration, Oral↗

PubMed2006

Rush hymenoptera venom immunotherapy is efficacious and safe.

BACKGROUND: Although rapid venom immunotherapy (VIT) protocols have been shown to be safe and effective, this issue has not yet been clarified in Turkey. OBJECTIVE: The aim of this study was to evaluate the side effects of rush VIT as well as early clinical and immunological responses in patients with a venom allergy. METHODS: Eighteen patients who had a history of severe systemic reactions after Hymenoptera sting were included in the study. The diagnosis was made on the basis of positive skin test reactivity and the presence of specific IgE in serum to either bee or vespid venoms. Fourteen patients underwent an average 7-day rush VIT regimen under careful monitoring in our clinic. Among them 7 patients were treated with Vespula species and 7 with Apis mellifera venom extracts. Four patients were followed up as a control group. Skin test response, specific IgE and IgG4 levels were determined before and after a year of VIT. Local and systemic reactions due to injections were monitored during the induction and maintenance phases of VIT. RESULTS: Specific IgG4 levels significantly increased after 1 year compared with levels before VIT (mean concentration before and after; 13.04 vs 21.85 mg/L, respectively; P < .05) whereas specific IgE levels did not change (11.54 vs. 13.32 kU/L). No significant differences were observed before and after one year of VIT in skin prick (2.34 vs 3.66 mm) and intradermal (0.12-0.11 microg/mL) test reactivities (P > .05). A single patient treated with bee venom developed 4 mild systemic reactions (4/469 injections, 0.85%) during the course of VIT. More local reactions occurred in patients receiving bee venom extract (3.33%) than in those receiving yellow jacket venom (1.33%). Two patients tolerated field stings without reactions. CONCLUSION: Our experience confirms that rush VIT is safe and has a low systemic reaction. It can be considered for patients requiring rapid protection.

Adolescent↗

PubMed2006

A hybrid expressing genetically engineered major allergens of the Parietaria pollen as a tool for specific allergy vaccination.

BACKGROUND: Allergy is an immunological disorder affecting about 25% of the population living in the industrialized countries. Specific immunotherapy is the only treatment with a long-lasting relief of allergic symptoms and able to reduce the risk of developing new allergic sensitizations and inhibiting the development of clinical asthma in children treated for allergic rhinitis. METHODS: By means of DNA recombinant technology, we were able to design a head to tail dimer expressing disulphide bond variants of the major allergen of the Parietaria pollen. IgE binding activity was studied by Western blot, ELISA inhibition assays and the skin prick test. T cell recognition was studied by peripheral blood mononuclear cell proliferation. The immunogenicity of the hybrid was studied in a mouse model of sensitization. RESULTS: In vitro and in vivo analysis showed that the disruption of specific cysteine residues in both allergens caused a strong reduction in IgE binding activity of the PjEDcys hybrid. In addition,we were able to show that a reduction in the IgE epitope content profoundly reduced the anaphylactic activity of the hybrid (from 100 to 1,000 times less than wild-type allergens) without interfering with the T cell recognition. Sera from BALB/c mice immunized with the hybrid were able to bind the natural Parietaria allergens and to inhibit the binding of human IgE to wild-type Par j 1 and Par j 2 allergens up to 90%. CONCLUSION: Our results demonstrate that hybrid-expressing disulphide bond variants of the major allergens of the Parietaria pollen displayed reduced allergenicity and maintained T cell reactivity for induction of protective antibodies.

Allergens↗

PubMed1999

Short-term preseasonal birch pollen allergoid immunotherapy influences symptoms, specific nasal provocation and cytokine levels in nasal secretions, but not peripheral T-cell responses, in patients with allergic rhinitis.

BACKGROUND: [corrected] Birch pollen allergic rhinitis can be sufficiently treated with specific subcutaneous allergoid immunotherapy (IT). However, little is known about the clinical and immunological effects of short-term therapy protocols. OBJECTIVE: To investigate the clinical efficacy of a birch pollen allergoid IT using seven preseasonal injections and to evaluate immunological parameters that might explain clinical findings. METHODS: Thirty-seven patients were included into the study and randomized to either a symptomatic treatment or allergoid IT plus symptomatic treatment. Patients were examined during the pre-IT season, at two extraseasonal visits both before and after IT and during the post-IT season. At each visit, nasal secretion samples were taken and analysed for levels of IL-4, IL-5 and IFNgamma. In addition, short-term birch-specific T-cell lines (TCLs) were cultured from peripheral blood mononuclear cells of 10 patients of the IT group, both before and after IT, and the ratios of lymphocyte subpopulations were determined. Cytokine production by TCLs (IL-4, IL-5, IFNgamma, IL-10) and proliferation of TCLs in response to stimulation with birch pollen allergen were measured. RESULTS: It was possible to evaluate 27 patients in accordance with the study protocol. Clinical symptoms and medication intake were reduced as a result of the IT as were nasal secretion levels of IL-5 (P = 0.007). IFNgamma was increased in nasal secretions (P = 0.01), while IL-4 was not measurable in most samples. No effect was found on proliferation of birch pollen-reactive TCLs, cytokine production by TCLs and the frequency and ratio of CD4+ and CD8bright or CD45RA+ and CD45RO+ cells in peripheral blood (all P > 0.05). Conclusion Preseasonal IT with a birch pollen allergoid is clinically effective in allergic rhinitis and influences cytokine production in the nose, but does not modulate the measured responses of peripheral blood T cells.

Allergens↗

PubMed2006

Long-term immunologic effects of broad-spectrum aeroallergen immunotherapy.

BACKGROUND: Limited data exist regarding extended, long-term immunologic effects of immunotherapy in polysensitized individuals. To study possible long-term effects, skin tests and specific IgE levels were obtained from subjects who had previously received broad-spectrum aeroallergen immunotherapy years before. METHODS: Eighty-two subjects (78% male, mean age 23 years) previously enrolled in a randomized, placebo-controlled trial of immunotherapy for treatment of childhood allergic asthma were reevaluated in adulthood (mean follow-up interval, 10.8 years) by puncture skin tests and CAP-RAST levels for major aeroallergens. All completed at least 18 months (median 27 months) of maintenance active treatment or placebo injections without subsequent immunotherapy. RESULTS: At adult follow-up, 36% of all skin tests to treatment allergens among subjects who received immunotherapy (n = 41) had significantly reduced intensity versus 26% of skin tests among placebo recipients (n = 41; p = 0.03). No significant differences were noted for individual treatment allergens. No significant differences were observed in the long-term changes of serum-specific IgE antibody levels for all treatment allergens between immunotherapy treatment and placebo groups (p = 0.43). The treatment and placebo groups had a similar acquisition of new skin test sensitivities from time of randomization in the original childhood trial to debriefing (15 vs. 20%; p = 0.28) and to adult follow-up (30 vs. 31%; p = 0.75). CONCLUSIONS: Immunotherapy suppresses skin test sensitivity 8-16 years after discontinuation of treatment, but long-term effects on specific IgE levels in serum are not observed. Broad-spectrum immunotherapy does not appear to affect the acquisition of new inhalant sensitivities.

Adolescent↗

PubMed2006

Phoenix sylvestris Roxb pollen allergy: a 2-year randomized controlled trial and follow-up study of immunotherapy in patients with seasonal allergy in an agricultural area of West Bengal, India.

BACKGROUND: Although the efficacy of allergen immunotherapy has been demonstrated in seasonal pollen allergy, there is no report of a double-blind placebo-controlled trial with standardized pollen extract in seasonal respiratory allergy from India. In the agricultural area of eastern India, Phoenix sylvestris Roxb or date sugar palm is grown or cultivated and seasonal allergic rhinitis is common during the pollen season. OBJECTIVE: The objective of the present study was to observe the clinical and immunological changes during a 2-year double-blind placebo-controlled trial of immunotherapy with standardized P sylvestris pollen extract in respiratory patients sensitive to pollen from this wild date palm. Thirty-five subjects with typical seasonal allergic rhinitis with or without bronchial asthma were selected. A symptom-medication score (based on a questionnaire and diary) was correlated with pollen counts as recorded in a Burkard sampler. Eighteen subjects were randomized to a specific immunotherapy (SIT) group receiving regular injections containing standardized allergen extract and 17 to a placebo control group. Changes in the level of specific immunoglobulin (Ig) E, IgG1, and IgG4 were recorded at 3-month intervals. Measurement of wheal diameter, total IgE level and forced expiratory volume in 1 second (FEV1) were performed before starting and a month after finishing therapy. RESULTS: The SIT group showed decreases of 33.5% and 57% from the baseline symptom-medication scores during the first and second treatment season, respectively. This group showed significant decreases in skin-reactivity to P sylvestris pollen extract and in specific IgE levels, and significant increases in FEV,, specific IgGI (1.95-3.2 times higher) and IgG4 (21.24-30.83 times higher). There were no significant changes in total IgE levels. The control group showed no significant changes for any parameter except the development of new sensitization in 2 cases (to Saccharum officinarum pollen grain and Alternaria species spores). The rate of local adverse reactions was 0.024%. CONCLUSION: After a 2-year study, allergen immunotherapy with standardized P sylvestris pollen extract was found to be effective in seasonal respiratory allergic subjects susceptible to P sylvestris pollen with a narrow range of sensitization.

Adult↗