House dust mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes.
BACKGROUND
Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT.


METHODS
Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG(4), nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples.


RESULTS
Decreased wheal sizes and VAS scores, negative challenges and increased sIgG(4) levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered.


CONCLUSIONS
Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal expression of FOXP3.
Clinical Hospital Sveti Duh, Zagreb, Croatia. branko.pevec @ gmail.com
Branko
B
Pevec
Mira
M
Radulovic Pevec
Asja
A
Stipic Markovic
Irena
I
Batista
Matija
M
Rijavec
Mira
M
Silar
Mitja
M
Kosnik
Peter
P
Korosec
D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D016022:Case-Control Studies; D045424:Complex Mixtures / Q000008:administration & dosage / Q000276:immunology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy; D000072181:Inositol Polyphosphate 5-Phosphatases; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008297:Male; D009299:Nasal Provocation Tests; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D012882:Skin Tests; D000072377:Syk Kinase; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D000098815:T-bet Transcription Factor
D000485:Allergens; D045424:Complex Mixtures; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D017455:Receptors, IgE; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases