Preliminary Study Of Clinical Phenotypes In Patients With Ankylosing Spondylitis

Research Background and Objective:Ankylosing spondylitis(AS)is a chronic inflammatory disease involving the spine and pelvis associated with autoimmunity,which is an important subtype of spondyloarthropathy 1.Although its etiology has not been found yet,a large number of studies have shown that genetic and environmental factors play an important role in the incidence and development of the disease,of which genetic factors are considered to be a major part.Genetic factors,gender,and early environmental factors are considered to affect AS susceptibility.HLA-B27 is considered to be a gene closely related to AS,and most patients with AS express HLA-B27(90%).However,the positive rate of HLA-B27 is less than 8%in the population 2.In addition to its diagnostic value,HLA-B27 is likely to be an important factor affecting the clinical phenotype of AS and disease susceptibility.Many studies indicate that AS patients in HLA-B27 positive have more severe clinical symptoms and imaging features than patients in HLA-B27 negative 3.Many reports have reported differences in the clinical phenotypes between HLA-B27 positive and negative patients.Some studies suggest that male patients in HLA-B27 positive are more than female patients 4.HLA-B27 positive patients are younger than HLA-B27 negative patients 5.Late-onset AS patients have a lower rate of HLA-B27 positive and a lower level of inflammatory cytokines,with fewer agents such as biologics or methotrexate 6.Studies in families and twins suggested that AS is genetically predisposed.And studies show that families with AS family history also have a more hereditary HLA-B27 positive than HLA-B27 negative 7.In a large study,it suggests that HLA-B27(+)AS patients have more symptoms of spinal,hip and peripheral involvement than HLA-B27(-)AS patients 8.In addition,AS is more common in young male patients,which has become a consensus.Epidemiological surveys show that the incidence of men and women is close to3:1~9.It indicates that sex plays an important role in the onset and prognosis of AS.Environmental factors are important factors in the pathogenesis of AS.In recent years,intestinal flora as an important factor in the establishment and development of immune function is widely studied.Many studies also suggest that factors such as birth ways,feeding methods and other factors lead to different types and compositions of bacteria in the early intestinal flora,which affects the earliest establishment of the immune system in the body.Studies have shown that breastfeeding can be a protective factor in the pathogenesis of AS 11.However,people know little about whether the mode of birth affects the risk of AS development.This paper is aimed to analyze the difference of clinical features in HLA-B27 and genders that affect the susceptibility to AS patients by analyzing the clinical data of patients with AS and using appropriate statistical methods.We explore the effect of delivery mode on the risk of AS by comparing other data,such as the mode of delivery in normal persons and AS patients.Therefore,on the one hand,we make retrospective studies to analyze the epidemiological characteristics of clinical phenotype of patients with AS.On the other hand,AS cases and control groups are foremed.Questionnaire is used to collect early environmental factors such as the mode of birth,pregnant weeks,etc.We also explore the effect of delivery mode on the incidence of AS.Methods:Part 1 Retrospective study of clinical phenotypes in patients with ASIn this study,we randomly selected 323 patients with AS who were admitted to the Department of Rheumatology and Immunization of Shanghai Changzheng Hospital from2008 to 2017 and conducted a cross-sectional retrospective study.Clinical data included age,gender,family history,past history of allergy,smoking history,HLA-B27,diagnosed intestinal inflammatory disease,diagnosed eye-related complications,treatment with NSAIDs,treatment with hormones,TNF-?antagonists using and so on.The differences of clinical data between patients with positive and negative HLA-B27 and other clinical data of patients with different gender were analyzed,respectively.Part 2 Delivery mode on the incidence of the risk of ASThrough the outpatient department and inpatient department,we included 116 cases of HLA-B27 positive AS patients from the Rheumatology and Immunology Department of Changzheng Hospital.A total of 207 persons,these patients'siblings who had not AS,were included as control group A rather than those with other rheumatic autoimmune diseases.Another 110 healthy people were included in the control group B.We collected the data of age,sex,height,weight,BMI,birth pattern,place of birth,pregnant months,birth months,and maternal age at delivery in case group and control group by telephone follow-up and questionnaire surveys.Sample T test analysis was used to explore the relevance between the incidence of AS and birth weight,birth months,gestational age,maternal age at delivery,birth patterns and other factors.Results:Part 1 Retrospective study of clinical phenotypes in patients with ASThe clinical data of 323 patients with AS who met 1984 Modified New York Criteria for AS were collected.First,patients were divided into two groups based on HLA-B27positive or negative.There was no significant difference in clinical features of AS family history,smoking,AS patients with intestinal complications or ocular complications rate,the use of NSAIDs and hormone drug ratio for two groups.The statistical analysis of the data showed that the positive rate of HLA-B27 in male patients(92.37%)was higher than that in female patients(81.61%)(?2=7.820,p<0.05).Patients with HLA-B27 positive had a lower rate of allergy than HLA-B27 negative patients(?2=9.500,p<0.001),but higher use rates of TNF antagonist(?2=9.500,p<0.001).The age of HLA-B27 positive patients(average age 39)was smaller than that of HLA-B27-negative patients(average age 46),p<0.05.On the other hand,there was no significant difference in AS family history,smoking history and the use of NSAIDs among different sexes according to sex grouping.Male patients had a lower rate of allergy than female patients(?2=6.773,p<0.05);Male AS patients(average age 39)were younger than female AS patients(average age 44),T=-2.483,p<0.05.The rate of use of TNF antagonist in male patients was higher than that of female patients(?2=21.056,p<0.001).However,hormone usage in female patients was higher than that of male patients(?2=8.094,p<0.05).There was no significant difference in the rates of intestinal complications between male and female AS patients,but the higher rate of eye complications in female AS patients than male AS patients(?2=5.495,p<0.05).Part 2 Delivery mode on the incidence of the risk of ASCompared with control group A,the cesarean section rate(6.90%)of 116 patients in the case group was higher than that of their siblings(0.97%),p<0.05.Compared with control group B,the cesarean section rate(6.90%)of 116 patients in the case group was also higher(0.91%)than that in unrelated healthy people(p<0.05).There was no significant difference in gender,body weight,height,BMI,birth weight and pregnant months between case group and control group B.However,by the independent sample t-test,the age of the case group was higher than that of the control group B,p<0.05.In addition,multivariate logistic regression analysis of the variables of sex,age stratification,BMI,birth pattern,birth weight,birth place,birth month,pregnant months in case group and control group B showed the following conclusions:The age in case group is larger than control group B;cesarean section and the occurrence of AS were related with each other;cesarean section rate in patients with AS were higher than control group B.Conclusion:Epidemiological surveys of clinical phenotypes suggest:1.HLA-B27 positive rate is closely related to gender,and male patients have a higher positive rate than female patients.2.Patients with AS HLA-B27 positive are younger than patients with AS HLA-B27negative.3.Male patients have higher rates in TNF antagonist usage than female patients,and TNF antagonist usage are more widely in HLA-B27-positive patients than negative patients.4.In the course of AS treatment,a small number of patients receive hormone therapy,which is more common in women than men.Our results suggest that caesarean section is a risk factor for AS,but further larger studies and experiments are needed to prove and explain this conclusion.