Kinetics and dynamic evaluation of specific immunotherapy.
Specific immunotherapy (SIT) is frequently used in the treatment of allergic diseases. However, the mechanisms by which SIT achieves clinical improvement remained unclear. We decided to study the in vivo kinetics of this therapy, using a nuclear medicine approach (leukocytes labelled with 99mTc-HMPAO) in patients on maintenance doses of specific immunotherapy with confirmed clinical efficacy.


METHODS
We studied 13 allergic patients grouped according to different treatment schedules: subcutaneous aqueous allergenic extract (3 latex and 2 hymenoptera venom), subcutaneous depot extract (2 house dust mite and 2 pollens), subcutaneous modified allergens (2 pollens), sublingual extract (2 house dust mites). The control group included two allergic patients submitted to subcutaneous injections of bacterial extract (1 patient--positive control), and aqueous solution (1 patient). At the same time that the therapeutic allergen was administered subcutaneously, the autologous labelled white cells were injected intravenously in a peripheral vein in the contralateral arm. A thoracic dynamic acquisition of 60 mins, 64x64 matrix, 2 frame/min, in anterior view was performed. Static acquisition for 256x256 matrix, during 5 mins each at 60, 90, 120, 180, 240, 300 and 360 mins after the administration of the radiolabelled leukocytes, in thoracic (anterior and posterior), and abdominal view were performed. During the examination, the local erythema was monitored. A similar procedure was undertaken for Sublingual administration of immunotherapy.


RESULTS
The inflammatory activity at the site of SIT injection (aqueous depot extract) started in the first hour and the increase was time related. For modified allergen extract and sublingual SIT the activity was present since the beginning of the administration. The ascendant lymphatic drainage, which was directed to the homolateral axillary region, to the lymphoid tissue of the upper mediastinum and to the anterior region of the neck began earlier. Thoracic focalisations were present for all the patients, whereas bowel focalisations were only observed for the subcutaneous route of administration. Sublingual SIT did not induce axillary or intestinal inflammatory focalisations, even though the patients had swallowed the allergenic extract. The uptake coefficient in individualized areas corrected to the uptake coefficient background was also studied.


CONCLUSIONS
For the subcutaneous route of administration, except for glutaraldehyde-modified allergen, the local inflammatory activity at the allergenic injection site was significantly higher in depth and was time dependent, maintaining activity even after complete disappearance of the erythema and/or wheal. These results express a prompt inflammatory involvement of the immune system with this allergenic therapy, which was unexpected until now. We also observed differences concerning allergic diseases, the type of allergenic extracts and routes of administration.
Pereira
C
C
Immunoallergology Department, Coimbra University Hospital, Pneumology Center, Coimbra University, Portugal.
Botelho
F
F
Tavares
B
B
Lourenço
C
C
Baeta
C
C
Palma-Carlos
A G
AG
Lima
J
J
Chieira
C
C
D000286:Administration, Sublingual; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001514:Bee Venoms / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002634:Chemotaxis, Leukocyte; D003692:Delayed-Action Preparations; D003888:Desensitization, Immunologic / Q000379:methods; D004890:Erythema / Q000209:etiology; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000000981:diagnostic imaging / Q000628:therapy; D007279:Injections, Subcutaneous; D007422:Intestines / Q000000981:diagnostic imaging / Q000276:immunology; D007700:Kinetics; D007840:Latex / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D020315:Latex Hypersensitivity / Q000000981:diagnostic imaging / Q000628:therapy; D017708:Leukocyte Transfusion; D008221:Lymphoid Tissue / Q000000981:diagnostic imaging / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011058:Pollen / Q000009:adverse effects; D039981:Pyroglyphidae; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime; D014018:Tissue Distribution; D014862:Wasp Venoms / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D000485:Allergens; D001514:Bee Venoms; D003692:Delayed-Action Preparations; D007840:Latex; D019275:Radiopharmaceuticals; D014862:Wasp Venoms; D019690:Technetium Tc 99m Exametazime