Three-year follow-up study of allergen-induced in vitro cytokine and signalling lymphocytic activation molecule mRNA responses in peripheral blood mononuclear cells of allergic rhinitis patients undergoing specific immunotherapy.
BACKGROUND
Allergen-specific immunotherapy (SIT) is known to affect the allergen-specific T helper cell (Th2/Th1) balance and to induce T regulatory (Treg) cells. These observations have usually been made during the first treatment year and often without symptom monitoring. This study was performed to investigate allergen-induced Th2 (IL-4, IL-5)-, Th1 [IFN-gamma, IL-18, signalling lymphocytic activation molecule (SLAM)]- and Treg (IL-10)-type immune responses in peripheral blood mononuclear cells (PBMC) and their association with symptom improvement in allergic rhinitis patients after 3 years of SIT.


METHODS
Twenty patients were treated with SIT and 8 patients were studied as untreated controls. PBMC were collected before and after 1 and 3 years of SIT and stimulated with specific allergen. Cytokine and SLAM mRNA expression was determined by TaqMan(R) RT-PCR. Symptoms were recorded yearly using visual analogue scale (VAS) scoring.


RESULTS
IL-18, SLAM and IL-10 mRNA expression increased after 3 years of SIT, with a peak at 1 year, whereas IL-5 mRNA expression transiently decreased and IFN-gamma mRNA expression transiently increased after 1 year of SIT. The increases in IL-18 and SLAM expression were not associated with symptom improvement, whereas decreases in both IL-4 expression and the IL-4/IFN-gamma ratio after 1 year of SIT were found in patients with a good therapeutic outcome (>40 percentage unit reduction in VAS).


CONCLUSIONS
SIT has long-term effects on allergen-specific immune responses. The induced Treg- and Th1-type responses persist over 3 years of SIT, whereas Th2-type responses are transiently decreased only during early therapy.
Nieminen
K
K
Department of Pulmonary Diseases and Clinical Allergology, University of Turku, FI-20520 Turku, Finland.
Laaksonen
K
K
Savolainen
J
J
D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003888:Desensitization, Immunologic; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D015703:Antigens, CD; D016207:Cytokines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1