Study On The Impact Of Streptococcal Infection On Generalized Pustular Psoriasis

Objectives : To figure out the relationship of phenotypes of generalized pustular psoriasis(GPP)in IL36 RN gene mutations;study on the level of serum IL36 Ra and IL36 gamma of pedigrees for GPP of different IL36 RN genotypes to illustrate the reasons why those normal people carrying IL36 RN gene mutations with no incidence of GPP;to clarify the impact of Group A beta-hemolytic streptococci(GAS)infection on GPP pedigrees and different IL36 RN genotypes of GPP patients.Methods:30 GPP patients and their parents were collected.The clinical data was recorded.Sanger sequencing was used on IL36 RN gene of the study group.In vivo,the peripheral blood of GPP pedigree was collected for ELISA,testing the level of serum IL36 Ra and IL36 gamma;in vitro,the peripheral blood mononuclear cells(PBMCs)of GPP pedigree were isolated,testing the proliferation of PBMCs mediated by streptococcal antigen with CCK8 method.Results:(1)In 30 cases of GPP patients and 32 cases of GPP parents,60% and 66% carried IL36 RN gene mutations.c.115+6T>C mutation rate was 48.3% and 31.25%,among which two GPP parents were normal people carring c.115+6T>C homozygous mutation.(2)Systemic inflammation(SI)was strong in GPP patients carrying IL36 RN mutation than that without mutations(P < 0.05),and so was the high proportion of geographic tongue(GT)(P < 0.05).The GT ratio was significantly higher in GPP patients with two mutations than that with one gene mutation.(P < 0.01);In 32 cases of GPP parents,the GT ratio of IL36RN-positive group was significantly higher than that of IL36RN-negative group(P < 0.05).(3)The proliferation of PBMCs in GPP patients was significantly higher than in GPP parents and healthy individuals on whole streptococcal antigen(SA)stimulation(P < 0.05),but this increased proliferation was attenuated after administration of whole SA treated with DNase-I(P > 0.05);non-NASA treatment significantly attenuated the enhanced PBMCs proliferation mediated by SA(P < 0.05);there was no significant difference of PBMCs proliferation among different IL36 RN genotype of GPP patients stimulated by SA and non-NASA(P > 0.05).(4)The serum IL36 Ra level was significantly lower in GPP patients than in GPP parents but higher than in healthy individuals(P < 0.05).IL36Ra/IL36 gamma was significantly higher in GPP patients than in healthy individuals(P < 0.05)and relatively lower than in GPP parents(P > 0.05).IL36Ra/IL36 gamma was significantly higher in GPP parents than in healthy individuals(P < 0.05);Compared IL36RN-positive GPP pedigree with IL36 RNnegative healthy individuals,the IL36 Ra level in GPP group was significantly lower than in GPP parents but significantly higher than in control group(P < 0.05);the IL36 Ra level of mutant type aa group in GPP was significantly lower than that of wild type AA group but significantly higher than that of control group(P < 0.05).Conclusions:(1)GPP patients carrying IL36 RN gene mutation had strong systemic inflammation(SI);(2)GPP IL36 RN mutation status and count were strongly associated with geographic tongue(GT);(3)Streptococcus infection could induce GPP and cells proliferation in immune responses was not associated with IL36 RN genotype;(4)Serum IL36 Ra and IL36Ra/IL36 gamma were strongly associated with GPP onset.The high level of IL36 Ra in GPP parents with IL36 RN mutation may be one of the reasons for no incidence of GPP.The serum IL36 Ra level was consistent with GPP genotype.