Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B-cell response in seasonal allergic rhinitis patients.

BACKGROUND: Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol. METHODS: In a prospective, dose-escalation study, 61 grass pollen-allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4 and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8). RESULTS: No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG4 levels were higher at V6 (8.1-fold, P < .001) and V8 (12.2-fold, P < .001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (-54.6%, P < .001) and V8 (-71.6%, P < .001) compared to V1. The absolute decrease in IgE-facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8. CONCLUSION: Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.

[Modern Diagnosis and Therapy of the rhinitis allergica]. / Moderne Diagnostik und Therapie der Rhinitis allergica.

The prevalence of allergic diseases is increasing worldwide. The highest increase rate is observed in rhinitis allergica. Apart from the anamnesis, the diagnosis relies mainly on skin tests, laboratory analyses and if necessary provocation tests. Symptomatic and causal therapy with abstention and specific immunotherapy are available as therapeutic means. Specific immunotherapy should be aspired as the method of choice. It is comprised of subcutane and sublingular immunity therapy. Usually native allergens and allergoids are used as therapeutics. Recombinant allergens are currently under development. Modern therapy procedures involving these drugs consist of year-round or pre- and co-seasonal treatment which spans at least 3-4 years. In cases of polyvalent allergy, different types of drugs and therapy procedures can be combined. The future of rhinitis allergica treatment lies in further development of specific immunotherapy.

Reflection of bounce phenomenon in TEOAE in humans: dependence upon test-stimulus parameters.

The bounce phenomenon signifies an alteration of hearing after presentation of low-frequency loud tones. Generally, it implies an initial improvement and a following reduction in auditory sensitivity that reaching peaks at 1- and 3-min intervals of the post-exposure time, respectively. The dependence of the bounce upon test-stimulus parameters has been investigated in the present study. Normally hearing subjects were tested and transiently evoked otoacoustic emissions, TEOAEs, were utilized for an objective assessment of the event. Clicks and tone-pips served for test-stimuli, i.e. for TEOAE registrations, while a tone of 250-Hz frequency and of 95-dB SPL intensity has been exposed during 3 min for the bounce initiation. Post-exposure TEOAE changes were more prominent at lower than at higher test-stimulus intensity, 15 vs. 35 dB nHL. The differences concerned both phases of the bounce, augmentations and reductions. On the other hand, under different test-stimulus frequencies, 250, 500, and 2000 Hz, the bounce, particularly augmentations, owned similar magnitudes. It has been concluded thus that the mechanism of the bounce, particularly of its augmentation phase, is global and covers all cochlear regions, tuned to different sound frequencies.