Anti-Saccharomyces cerevisiae Antibodies Associate with Phenotypes and Higher Risk for Surgery in Crohn’s Disease: A Meta-Analysis

Zhang, Zhaoxia; Li, Chen; Zhao, Xinmei; Lv, Chaolan; He, Qiong; Shan, Lei; Guo, Yandong; Zhi, Fachao

doi:10.1007/s10620-012-2244-y

Cited by 61 publications

(43 citation statements)

References 53 publications

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“…The best characterized of the serological markers of CD is ASCA, which can be used for differential diagnosis between CD and ulcerative colitis, and also for the prediction of disease course (19,20). Abs against several other commensals linked to CD were also found in APECED patients.…”

Section: Discussionmentioning

confidence: 99%

“…This is best characterized in Crohn's disease (CD), in which Abs against several species of gut normal flora have been used as a diagnostic aid and in the prediction of disease progression (19,20). Although the pathogenetic significance of these serological markers in CD remains controversial, large-scale genetic association studies have identified variants of innate pattern recognition receptors as risk factors (21), supporting the role of antimicrobial responses in the pathogenesis.…”

mentioning

confidence: 99%

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Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy Patients

Hetemäki

Jarva

Kluger

et al. 2016

The Journal of Immunology

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Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p < 0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti–IL-17 or –IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti–S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO+ population (ρ = −0.706; p < 0.01). APECED patients also had decreased numbers of FOXP3+ cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn’s disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy Patients

Hetemäki

Jarva

Kluger

et al. 2016

The Journal of Immunology

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“…Оказа-лось, что ASCA-положительный статус являлся фак-тором риска для начала БК в раннем возрасте, вовлечения подвздошной кишки, развития ослож-ненной формы болезни, перианальной БК и по-требности в хирургическом лечении [67].…”

Section: серологические маркерыunclassified

Prognostic Factors in Crohn’s Disease

Щукина¹

2016

Alʹm. klin. med.

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ВВЕДЕНИЕБолезнь Крона (БК) -многофакторное гетероген-ное заболевание с прогрессирующим течением, ха-рактеризующееся хроническим воспалением желу-дочно-кишечного тракта (ЖКТ) [1]. За десятилетний период наблюдения стриктурирующие или пене-трирующие осложнения развиваются у каждого второго пациента с БК, а частота рецидивирования достигает 90% [2].С появлением терапии, способной приостано-вить прогрессирование БК, оценка прогноза на ран-ней стадии приобретает большое значение для раз-работки плана лечения с учетом степени тяжести заболевания [3,4,5,6,7,8]. В проведенных исследо-ваниях предложено множество определений небла-гоприятного (прогрессирующего) или тяжелого (ин-валидизирующего, осложненного) течения БК, сформулированных на основании особенностей раз-вития болезни в процессе определенного периода наблюдения. При этом оценивалось изменение фе-нотипа БК, то есть переход воспалительной формы заболевания в стриктурирующую или пенетрирую-щую форму с развитием соответствующих этим фор-мам осложнений, которые могут способствовать не-обратимому повреждению ЖКТ. Определялась также потребность в госпитализации, в хирургиче-ском лечении, учитывались отсутствие ответа на те-рапию, непрерывное или часто рецидивирующее течение, наличие тяжелых внекишечных проявле-ний, развитие стероидозависимости или стероидо-резистентности, необходимость раннего назначения стероидов и иммуносупрессоров, низкое качество жизни и др. ГЕНДЕРНЫЕ РАЗЛИЧИЯ И ПРОГНОЗ БОЛЕЗНИ КРОНАВ нескольких источниках литературы содержатся данные, свидетельствующие о наличии связи меж-ду гендерными различиями и исходами БК. N. Gupta и соавт. показали повышенный риск хи-рургических вмешательств у больных БК женского пола в педиатрической практике [9], в то время как в двух других исследованиях фактором риска хи-рургического лечения [10,11] PROGNOSTIC FACTORS IN CROHN'S DISEASE Shchukina O.B.North-Western State Medical University named after I. I. Mechnikov; 41 Kirochnaya ul., Saint-Petersburg, 191015, Russian Federation The paper contains a review of the literature data concerning the demographic, clinical, laboratory, genetic, immunohistochemical, endoscopic, and imaging features with a potential role of prognostic factors for clinical management of patients with Crohn's disease.

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“…A number of systematic reviews and meta-analyses provide detailed information regarding the results of numerous studies conducted over the past 20 years to assess the clinical utility of serological markers, so we address this topic here only briefly. [11][12][13][14] The earliest described and best characterized serological markers for IBD are anti-Saccharomyces cervisiae antibody (ASCA) and atypical perinuclear anti-neutrophil Key points ■ Basic science advances herald an era in which IBD will be subcategorized on the basis of the involvement of specific molecular pathways ■ Knowledge of variation in IBD-susceptibility genes has expanded our understanding of the biological pathways relevant to disease susceptibility and to clinical phenomena including disease location and therapeutic response ■ Multimodal algorithms that combine clinical and genetic information will show utility in diagnostic panels and for predicting disease course and therapeutic response ■ Gene expression signatures and composite models that reflect the influence of environmental factors, such as the microbiome, show promise as tools for individualized risk stratification and treatment selection cytoplasmic antibody (pANCA). [15][16][17][18] ASCA is primarily associated with Crohn's disease and pANCA with ulcerative colitis.…”

Section: Serological Markersmentioning

confidence: 99%

“…[11][12][13][14] In brief, pANCA seropositivity is associated with treatment-resistant ulcerative colitis and the development of pouchitis following colectomy with ileal pouchanal anastomosis; chronic pouchitis is associated with high pANCA titres. 110,111 Complications such as strictures, fistulas, and abdominal surgery have been associated most consistently with seropositivity for ASCA but also with several of the other anti-glycan antibodies as well as antibodies to CBir1, OmpC, and I2.…”

Section: Predicting the Clinical Course Of Ibdmentioning

confidence: 99%

Towards personalized care in IBD

Gerich

McGovern

2013

Nat Rev Gastroenterol Hepatol

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The expanding knowledge of the role of genetic variants involved in the susceptibility to IBD heralds an era of disease categorization beyond Crohn's disease and ulcerative colitis. A more robust molecular definition of the spectrum of IBD subtypes is likely to be based on specific molecular pathways that determine not only disease susceptibility but also disease characteristics such as location, natural history and therapeutic response. Evolving diagnostic panels for IBD will include clinical variables and genetic markers as well as other indicators of gene function and interaction with environmental factors, such as the microbiome. Multimodal algorithms that combine clinical, serologic and genetic information are likely to be useful in predicting disease course. Variation in IBD-susceptibility and drug-related pathway genes seems to influence the response to anti-TNF therapy. Furthermore, gene expression signatures and composite models have both shown promise as predictors of therapeutic response. Ultimately, models based on combinations of genotype and gene expression data with clinical, biochemical, serological, and microbiome data for clinically meaningful subgroups of patients should permit the development of tools for individualized risk stratification and treatment selection.

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Anti-Saccharomyces cerevisiae Antibodies Associate with Phenotypes and Higher Risk for Surgery in Crohn’s Disease: A Meta-Analysis

Cited by 61 publications

References 53 publications

Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy Patients

Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy Patients

Prognostic Factors in Crohn’s Disease

Towards personalized care in IBD

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