IL-10 And The SNPs In Promoter Are Associated With Specific Antibodies In Serum Of Penicillin Allergic Patients

To elucidate the underlying mechanism of allergic reaction to penicillins, we explored the relationship between IL-10 and specific antibodies in patients with penicillin allergy. We examined IL-10 level in serum of 102 patients and 86 control subjects by enzyme linked immunosorbent assay (ELISA), and two single nucleotide polymorphisms (SNPs) at positions -1082G/A, -819C/T in the promoter region of the IL-10 gene by sequence-specific primers polymerase chain reaction (SSP-PCR). And then, we analyzed the result comparing with the date of eight kinds of specific IgE and IgG antibodies of different antigenic determinants in serum (BPO-PLL, PVO-PLL, APO-PLL, AXO-PLL, BPA-PLL, PVA-PLL, APA-PLL, AXA-PLL) ourresearch group determined before..1. Associations between penicillin allergy and IL-101.1 Associations between penicillin allergy and IL-10 level in serumWe grouped 102 patients into positive group with skin test and patients groupwith allergic history. Among the patient group cases with anaphylactic shock, urticaria and other symptoms were 14,25 and 8. According to allergic reaction types, there were 25 patients with immediate hypersensitivity reaction and 22 with delayed hypersensitivity reaction. The level of IL-10 in serum is different in every groups and control group, but the difference is too little to show significant association between allergic symptoms and IL-10 production (P>0.05). 1.2 Associations between penicillin allergy and SNPs in promoter region of IL-10In our study, we found G/G, G/A, A/A and C/C, C/T, T/T genotype in promoter region -1082G/A and -819C/T position of the IL-10 gene. But the allele frequency and genotype distribution is not significantly different between every symptom groups and the control population (p>0.05). 2. Associations between specific IgE antibodies and IL-10 2.1 The relationship between IL-10 level and specific IgEThere were significantly lower IL-10 level in allergic patients with positive specific IgE antibodies compared to normal controls (P<0.01), and a same result was observed in allergic patients with positive specific IgE antibodies compared to allergic patients with negative specific IgE (P<0.01). The result showed that the decrease of IL-10 level might be associated with allergy of positive specific IgE antibodies.According to the different number of positive specific IgE antibodies, the allergic patients with positive specific IgE antibodies were divided into groups with 1, 2, 3 or more positive specific IgE antibodies. Patients with 3 or more positive specific IgE antibodies had significantly lower IL-10 levels than normal controls (P<0.01).2.2 The correlations between specific IgE and SNPs in promoter region of IL-10The significantly different distributions of -1082G/A SNPs genotype were observed between patients with positive specific IgE and normal controls (P<0.01). Similar results were observed between patients with positive specific IgE and patients with negative specific IgE (P<0.01).The significantly different frequencies of -1082 G/A allele were observed between patients with positive specific IgE and normal controls (P<0.01). Similar results were observed between patients with positive specific IgE and patients with negative specific IgE (p<0.01).These observations showed that the SNP at -1082 G/A position in promoter region of IL-10 gene was associated with the production of specific IgE antibodies. 3. Associations between specific IgG antibodies and IL-10 3.1 The relationship between IL-10 level and specific IgGThere were significantly lower IL-10 level in allergic patients with positive specific IgG antibodies compared to normal controls (P<0.05), and a same result was observed in allergic patients with positive specific IgG antibodies compared to allergic patients with negative specific IgE (P<0.05). The result showed that the decrease of IL-10 level might be associated with allergy of positive specific IgG antibodies.According to the different number of positive specific IgG antibodies, the allergic patients with positive specific IgG antibodies were divided into groups with 1, 2, 3 or more positive specific IgG antibodies. But there is nor significant differencebetween every group.3.2 The correlations between specific IgG and SNPs in promoter region of IL-10The significantly different distributions of -1082 G/A SNP genotype were observed between patients with positive specific IgG and normal controls (P<0.01). Similar results were observed between patients with positive specific IgG and patients with negative specific IgG (P<0.01).The significantly different frequencies of -082 G/A and -819 C/T allele were observed between patients with negative specific IgG and patients with positive specific IgG (P<0.01); while only -819 C/T allele were observed difference between patients with negative specific IgG and normal controls (P<0.01).These observations show that SNPs of both -1082G/A and -819C/T in promoter region of IL-10 were associated with the production of specific IgG antibodies. 4. Association between IL-10 and polymorphismsWe divided control and patients into three groups according to -1082 G/A genotypes GG GA AA. Both in control and in patients, the GG groups had the high levels of IL-10, and the differences had statistal signification. But in -819 C/T position, we could not confirm the existing of this difference.These observations showed that the genotype GG and GA at -1082 G/A in IL-10 promoter region were associated with high level of IL-10.Conclusion: This study shows that the type of positive specific IgE and IgG are associated with the decrease of IL-10 level in allergic reaction to penicillin. There is a declining trend in IL-10 serum level with the increase of number of positive specificIgE and IgG The decline of IL-10 level has significant correlations to the rise of four kinds specific IgE.Other observations about SNPs in promoter region of IL-10 gene suggest that the distribution of genotype and frequency of allele at -1082G/A position may be associated with the production of both specific IgE and IgG antibodies; while the distributions of genotype and frequency of allele at -819C/T position may have a correlation only to specific IgG antibodies. The GG and GA genotypes may relat with high level of IL-10.