Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy.
BACKGROUND
Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy.


METHODS
A total of 34 children (6-18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgG(Mite) and IgG4(Mite), by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3.


RESULTS
There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgG(Mite) (p < 0.001) and specific IgG4(Mite) (p < 0.001) significantly increased after 8 weeks, while it took 12 weeks in the classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups.


CONCLUSIONS
Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients.
Schubert
R
R
Paediatric Pulmonology and Allergology, Department of Internal Medicine III, J.W. Goethe University, Frankfurt am Main, Germany. ralf.schubert@kgu.de
Eickmeier
O
O
Garn
H
H
Baer
P C
PC
Mueller
T
T
Schulze
J
J
Rose
M A
MA
Rosewich
M
M
Renz
H
H
Zielen
S
S
D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D060829:Arthropod Proteins; D001249:Asthma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D001944:Breath Tests; D002648:Child; D003546:Cysteine Endopeptidases; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D047150:Eosinophil Cationic Protein / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D060149:Tetraspanin 30; D000098815:T-bet Transcription Factor
D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C554586:CD63 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D007074:Immunoglobulin G; D015289:Leukotrienes; D010980:Platelet Membrane Glycoproteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D060149:Tetraspanin 30; D009569:Nitric Oxide; D007073:Immunoglobulin E; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1