Study On The Relationship Between IL-31 And Pruritus Of Bullous Pemphigoid And Their Mechanism Of Action

Objective:To observe the expression of serum interleukin 31(IL-31),serum total immunoglobulin E(IgE)levels,and eosinophil levels in peripheral blood and skin lesions in patients with bullous pemphigiod(BP),and the degree of itching in patients;also observe the expression and distribution of IL-3l functional receptor A(IL-3IRA)in BP patients and normal skin,and explore IL-31 and BP itching,IgE,EOS The relationship and the possible mechanisms of action involved in BP itching.Methods:During the period from October 2016 to November 2018,64patients(BP group)who were diagnosed as bullous pemphigiod for the first time in the Department of Dermatology,the Fourth Hospital of Hebei Medical University,and the 60 elderly persons(NC group)who randomized physical examination in our hospital during the same period.Both of two groups Clinical general data and peripheral blood samples were collected.Meanwhile the clinical data of BP group were analyzed,including the number of eosinophils in peripheral blood and skin lesions,the degree of itching and the pruritus score and pathological data collection.The levels of serum IL-31 and total serum IgE in all specimens were detected by ELISA.At the same time,20cases of typical skin lesions(blister)in the above BP group and 20 cases of normal skin in outpatient surgery were collected.Immunohistochemistry was used to detect the expression and distribution of IL-3l receptor A(IL-3IRA)in skin lesions of BP patients and normal skin.The data were processed by SPSS21.0 software,and the correlation between IL-31 in serum of BP patients and BP itching,IgE,and EOS was obtained.The data of the two groups were compared by t test or rank sum test,and the data of multiple groups were analyzed by analysis of variance or rank sum test.Result:1 Clinical data analysis:1)General:Among the 64 BP patients,35 were male(54.69%),29 were female(45.31%),and the ratio of male to female was 1.2:1.The age range is29-94 years old and the mean is(73.11±10.96)years old.There were 56patients over the age of 60,accounting for 87.5%of the total.64 patients had varying degrees of itching and moderate to severe itching.2)The EOS levels in peripheral blood:Among 64 patients with BP,21patients(32.81%)had an increased absolute number of EOS(>0.52×10~9/L);There were 21 patients(32.81%)whose absolute number of EOS was in the normal range[(0.02-0.52)×10~9/L];There were 22 patients(34.38%)with a decrease in absolute number of EOS(<0.52×10~9/L).3)Peripheral blood EOS levels were positively correlated with pruritus(r_s=0.513,P<0.01).2 Experimental results:2.1 The results of serum IL-31 and total IgE levels in BP group and NC group were measured by ELISA.1)The serum IL-31 levels in the BP group(40.05±10.24 pg/ml)was higher than that in the NC group(18.89±1.72 pg/ml),the difference was statistically significant(P=0.037);The serum total IgE levels in the BP group(368.3±83.58 ng/ml)were significantly higher than those in the NC group(80.76±12.54 ng/ml),and the difference was statistically significant(P<0.01).2)Serum IL-31 levels in the BP group were associated with pruritus(P=0.033):There was a statistically significant difference in serum IL-31 levels between the mild pruritus group and the moderate pruritus group,and between the mild pruritus group and the severe pruritus group(The P values were 0.014and 0.008 respectively,and the serum IL-31 levels in the moderate and severe pruritus groups were significantly higher than those in the mild pruritus group.There was no significant difference in serum IL-31 levels between the moderate pruritus group and the severe pruritus group(P=0.057).3)There was no correlation between serum IL-31 expression and serum total IgE levels in BP patients(r_s=0.088,P=0.636).4)There was a correlation between serum IL-31 levels and peripheral blood EOS levels in BP patients(r_s=0.674,P<0.01);The serum IL-31 levels in BP patients with EOS infiltration in lesions were significantly higher than those without EOS infiltration in lesions.The difference was statistically significant(P=0.021).2.2 Immunohistochemistry resultsThe IL-3IRA was expressed in skin epidermal keratinocytes of both groups.The expression of IL-3IRA in BP lesions was significantly higher than that in normal subjects(P<0.01),and There was a strong expression of IL-3IRA in the EOS in the BP patients lesion.Conclusion:1.The bullous pemphigoid patients are more common in the elderly,no significant gender differences,often accompanied by itching symptoms.2.About 1/3 BP patients with elevated peripheral blood EOS levels,and the degree of pruritus in BP patients was positively correlated with EOS in peripheral blood3.The serum IL-31 levels in BP patients were associated with pruritus and no correlation with serum total IgE levels,suggesting that IL-31 may be an independent pruritic factor of BP and does not depend on serum total IgE levels.4.The serum IL-31 was positively correlated with EOS,and the serum IL-31 levels of BP patients with EOS infiltration in lesions was significantly higher than that without EOS infiltration,suggesting that EOS may be one of the sources of IL-31 in BP.