背景与目的 肠易激综合征（IBS）的发病机制包括脑-肠互动异常、内脏高敏感、肠道动力异常、炎症免疫激活、肠道菌群失调等。IBS患者血清中存在自身抗体、肠黏膜存在免疫活化状态，提示自身免疫因素可能对IBS发生、发展产生影响。本研究通过分析IBS患者血清中差异性抗体与临床症状的关系，为挑选有研究价值血清差异性抗体进行病理生理学研究，评估免疫因素对IBS发生发展的影响提供证据。

方法  针对本中心前期应用HuProt^TM芯片鉴定发现的IBS患者血清中与健康对照者有显著差异的14种IgG型和IgA型差异性抗体，检索Gene数据库和PubMed数据库靶抗原生物基因信息和对应靶抗原功能相关研究论文，汇总分析，计算255例IBS患者血清差异性抗体阳性数目，并进行对应靶抗原的功能分群，提取IBS患者症状发作规律调查问卷的临床数据，通过独立样本检验、Mann-Whitney U检验、²检验或Fisher精确检验，分析血清差异性抗体阳性患者和阴性患者临床表现的异同。

结果 血清中差异性IgG型抗体种类多（＞3种）的IBS患者病程显著长于血清差异性IgG抗体少（≤3）的IBS患者（11.6±9.9年比6.7±6.3年，P=0.004）。血清差异性IgA型抗体种类多的IBS患者症状发作时排水样便的患者百分比显著高于血清差异性IgA抗体种类少的IBS患者（27.3%比11.1%，P=0.028）。

血清差异性抗体对应靶抗原功能为促细胞凋亡类的IBS患者平时腹痛/腹部不适频率、平时腹痛程度为重度的患者百分比显著低于相关抗体阴性组。血清差异性抗体对应靶抗原功能为抑制细胞凋亡类的IBS患者排便后症状完全缓解的患者百分比显著低于相关抗体阴性组。血清差异性抗体对应靶抗原与炎症免疫相关的IBS患者排便前出现腹痛的患者百分比显著低于相关抗体阴性组。血清差异性抗体对应靶抗原功能与神经递质传递相关的IBS患者平时腹痛/腹部不适频率显著低于相关抗体阴性组。

IBS患者血清中IgG 型ELAVL4抗体阳性者病程较对应抗体阴性组更长（P=0.046）。IBS患者血清IgA型ANXA1抗体阳性组发作时排水样便患者百分比显著低于对应抗体阴性组（P=0.042）。血清IgA型EXOSC5抗体阳性者排便前腹痛、腹部不适比例、平时腹痛/腹部不适频率、平时每日有腹痛/腹部不适比例均显著低于对应抗体阴性组（P=0.001、P=0.028、P=0.023、P=0.046）。血清IgA型PTRH2抗体阳性者IBS肠道主要症状计分、排便前腹痛/腹部不适为中重度患者百分比显著低于对应抗体阴性组（P=0.023、P=0.046）。血清IgA型RIOK1抗体阳性者肠道主要症状计分高于对应抗体阴性组（P=0.004），血清IgA型RIOK1抗体阳性者发作时排水样便患者百分比、血清IgG型RIOK1抗体阳性者排便前腹痛患者百分比均显著低于对应抗体阴性组（P=0.000、P=0.001）。IBS患者血清IgA型ZNF667抗体阳性者排便前腹痛患者百分比显著低于对应抗体阴性组（P=0.001）。IBS患者血清IgA型ZNF667抗体阳性者平时腹痛频率低于对应抗体阴性组（P=0.042）。

 结论  IBS患者血清中IgG型抗体数量与IBS病程有关，IBS患者血清中IgA型抗体数量与IBS肠道症状严重程度相关。IBS患者血清中促凋亡靶抗原对应的差异性抗体与患者肠道症状有一定相关性。血清IgG型ELAVL4、IgA型ANXA1抗体、IgA型EXOSC5、IgA型PTRH2抗体、IgA型和IgG型RIOK1抗体、IgA型ZNF667等抗体与IBS患者临床症状有一定相关性。

background & ive the pathogeneses of irritable bowel syndrome (ibs) include disorders of gut-brain interaction, visceral hypersensitivity, gastrointestinal motility disorders, altered inflammatory activities and immune status, dysbiosis. autoantibodies existing in the sera and the activation of intestinal mucosal immune in ibs patients suggest that autoimmunity may play a role in the onset and progression of ibs. the aim of this study is to analyze the association of the sera autoantibodies with clinical manifestations of ibs patients and to identify the candidate antibodies for further study to reveal the possible immune pathogenesis.

material and methods in the previous studies, 14 different kinds of igg and 14 different kinds of iga antibodies were identified from sera of ibs patients while comparing with hcs by huprot^tmmicroarray. we searched for the genetic information and functions of corresponding target antigens in gene database and pubmed database, counted the numbers of positive sera antibodies in ibs patients and classified the antibodies as functional clusters according to the corresponding target antigens. clinical data of ibs patients were extracted from the database. we compared the clinical manifestations between the ibs patients with and without sera differential antibodies using independent sample test, mann-whitney u test, χ2 test or fisher exact test. 

results ibs patients having 3 or more kinds of sera igg differential antibodies present longer disease course than those having less types of sera igg antibodies (11.6±9.9 vs 6.7±6.3 years, p=0.004). in group of patients having more kinds of sera iga differential antibodies, more proportion of ibs patients pass watery stools while ibs onset comparing to those patients having less types of sera iga antibodies (27.3% vs 11.1%, p=0.028). 

the ibs patients having sera differential antibodies and the corresponding target antigens clustering as pro-apoptotic antigens present lower frequency of abdominal pain/ discomfort and less proportion of patients reported severe abdominal pain than those without this kind of antibodies. among ibs patients having sera antibodies with corresponding target antigens clustering as inhibitory apoptosis, the proportion of patients reported complete remission of abdominal pain /discomfort after defecation are lower than those without this kind of antibodies. in ibs patients having differential antibodies and the corresponding target antigen clustering as inflammatory immunity, lower proportion of patients reported defecation-associated abdominal pain than those without this kind of antibodies. ibs patients with antibody of target antigens associated to neurotransmitters transmission present significant lower frequency of abdominal pain/ discomfort than those without this kind of antibodies.

the disease course of ibs in patients with sera elavl4-igg antibody is significant longer than those patients with this antibody (p=0.046). ibs patients with anxa1-iga antibody present significant lower proportion of watery stools while ibs onset than those without this antibody (p=0.042). in cases with sera exosc5-iga antibody, the proportion of patients with defecation-associated abdominal pain, proportion of patients with defecation-associated abdominal discomfort, frequency of ordinaryabdominal pain/discomfort and proportion of patients with daily ordinaryabdominal pain/discomfort are lower than those without this antibody (p=0.001, p=0.028, p=0.023, p=0.046). patients with ptrh2-iga antibody have significant lower score of bowel symptoms and lower proportion of patients with moderate-severe abdominal pain than those without this antibody (p=0.023, p=0.046). patients with sere riok1-iga antibody have significant higher score of bowel symptoms than those without this antibody(p=0.004), the proportion of patients with passing watery stools while ibs onset in riok1-iga positive patients and the proportion of defecation associated abdominal pain in riok1-igg positive patients are much lower than those without these antibodies (p=0.00003, p=0.001). lower proportion of ibs patients with znf667-iga antibody reported defecation-associated abdominal pain/ discomfort (p=0.001), and less frequency of ordinaryabdominal pain/ discomfort in patients with znf667-iga antibody (p=0.042) than those without corresponding antibodies.

conclusions the amounts of sera igg autoantibodies in ibs patients are associated with disease course, while the amounts of sera iga antibodies are correlated to the severity of intestinal symptoms. the antibodies in sera of ibs patients with apoptosis-associated target antigens are more relevant to the bowel symptoms. there are correlations between the sera antibodies of elavl4-igg, exosc5-iga, ptrh2-iga, anxa1-iga, riok1-iga, riok1-igg, znf667-iga and bowel symptoms in ibs patients.