| Abstract: |
SUMMARY AND CONCLUSIONAtopic diseases are complex familial disorder with multiple manifestations. The aim of this work was to identify several immunological and biochemical markers in atopic asthma, atopic dermatitis, and atopic rhinitis and its relation to disease severity; and also to genotype R576 IL-4Rα allele and to clarify its segregation with atopic diseases and its usefulness as a clinical marker of atopic diseases. The immunological and biochemical markers had been planned to include serum interleukin-4 (IL-4), peripheral blood eosinophil cell count, serum eosinophil cationic protein (ECP) (as a marker of eosinophil activity), serum total immunoglobulin E (IgE) and specific IgE by skin testing. The genetic variation in IL-4 function aimed to provide a mean of assessing the genetic mechanisms that underlie the patho-physiology of atopy.The present study was carried out at the Medical Biochemistry Department and Chest Clinic, Dermatology Clinic, ENT Clinic, and the Allergy Clinic of Allergy and Immunology Unit of Chest Department, Faculty of Medicine, Zagazig University. Seventy five patients suffering from atopic disorders and 25 age-matched healthy unrelated volunteers taken as a control group. The atopic patients were planned to include nonsmoker patients with no parasitic infestation; 25 atopic asthmatics (asthma group), 25 patients with atopic dermatitis, and 25 patients with atopic rhinitis.Full history and clinical examination, laboratory investigations were done to all patients including: complete blood picture, stool and urine analysis, determination of total IgE and IL-4 by ELISA, determination of specific IgE by prick skin test, determination of R576 IL-4 α allele by PCR-based restriction fragment length polymorphism, determination of eosinophil cationic protein by chemoluminescence technique. For asthmatic patients, chest X-ray and pulmonary function tests were done.The results of this study showed that the most common allergens causing (+ve)skin test among atopic patients were mixed pollens (46.6%), hay dust (33.3%), smoke (21.3%), house dust mite (18.6%) and mixed fungus (16%), cotton and wool (9.3%), mixed feather (6.6%), and animals dander (5.3%).There was a statistically significant association between R576 allele and atopy as compared with control group (p < 0.001 in all atopic groups). There was also a significant association between homozygosity for the R/R576 allele and atopy (p was 0.02 in asthma group, 0.02 in atopic dermatitis group, and 0.03 in atopic rhinitis group). The relative risk of R576 allele in atopy was 4.2 in asthmatic group, 7.3 in atopic dermatitis group, and 4.8 in atopic rhinitis group. For homozygous R/R576, there was a statistically significance for the severe versus mild disease (p = 0.02 in asthma group, 0.03 in atopic dermatitis group, and 0.03 in atopic rhinitis group).There was a statistically significant increase level of serum IL-4 in atopic patients when compared with controls (p < 0.001 in all atopic groups), but there was no significant correlation between serum IL-4 levels and severity of atopic diseases. Also, there was no statistically significant difference between the serum IL-4 values and allelic variants in all atopic groups.There was a statistically significant increase level of serum ECP in atopic patients when compared with controls (p < 0.001 in all atopic groups), also there was a highly significant correlation between serum ECP levels and severity of atopic diseases (p < 0.001 in all atopic groups). There was a highly significant increase in the serum ECP levels towards homozygous in R576/R576 atopic patients, (p < 0.001 in all atopic groups)There was a statistically significant increase level of peripheral blood eosinophils cell count in atopic patients when compared with controls (p < 0.001 in all atopic groups), also there was a highly significant correlation between peripheral blood eosinophils cell count levels and severity of atopic diseases (p < 0.001 in all atopic groups). There was a highly significant increase in the peripheral blood eosinophils cell count levels towards homozygous in R576/R576 atopic patients, (p < 0.001 in all atopic groups).There was a statistically significant increase level of serum total IgE in atopic patients when compared with controls (p < 0.001 in all atopic groups), also there was a highly significant correlation between serum total IgE levels and severity of atopic diseases (p < 0.001 in all atopic groups). There was a highly significant increase in the serum total IgE levels towards homozygous in R576/R576 atopic patients, (p < 0.001 in all atopic groups).There was no statistically significant correlation between serum IL-4 and serum ECP, peripheral blood eosinophils cell count, or serum total IgE and there was there was no statistically significant difference between the serum IL-4 values and allelic variants in atopic patients. There was a significant positive correlation between serum ECP and peripheral blood eosinophil cell count, and serum total IgE; there was also a significant positive correlation between peripheral blood eosinophil cell count and serum total IgE in atopic patients. A highly significant increase towards homozygous R/R576 in atopic patients was found with serum ECP, peripheral blood eosinophil cell count, and serum total IgE.In conclusion, the current findings demonstrated that the presence of R576 allele correlates with atopic diseases severity and thus act as a disease modifier. One or two copies of R576 were associated with more severe disease. Thus the R576 allele is an atopy susceptibility gene that is strongly associated with atopy and a disease-modifying gene that is not causative but modify the phenotype of the disease and may be a useful genetic marker and may also, it acts as a drug-modifying gene that alter the response to pharmacologic agents in affected individual. This genetic study hoped that further studies will define new targets for the next generation of allergy therapeutic agents. Because there are conflicting results for the relation of peripheral blood eosinophils cell count and serum total IgE with atopy, ECP is the most useful biochemical marker for atopic disease activity. But IL-4 is a marker of TH2 activity but not correlated with disease severity, so new important therapeutic strategies for the treatment of atopic diseases is redirection the imbalance between TH2 and T regulatory cells; Tregs (Tr1 and TH3) to block TH2 differentiation is a new target of therapy.
|
|
|