Diagnostic Significance of Positive Anti-endomysium Antibodies in the Culture Medium of the Intestinal Biopsies in Not-Celiac Wheat Sensitivity (NCWS)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Changes in the intestinal histology of NCWS patients who tested positives for EmAs in the culture medium of the intestinal biopsies, at the time of the first evaluation.
研究概览
简要总结
The most frequent diseases caused by wheat ingestion are T cell-mediated disorders, i.e. celiac disease and immunoglobulin E (IgE)-mediated allergic reactions. However, besides celiac disease and wheat allergy, there are cases of gluten reactions in which neither autoimmune nor IgE-mediated allergic mechanisms are involved. These are generally defined as GS or Not-celiac wheat sensitivity (NCWS). Typically, NCWS diagnosis is made by exclusion, and an elimination diet and an "open challenge" (i.e., the monitored reintroduction of gluten-containing foods) are most often used to evaluate whether health improves or worsen with the elimination or reintroduction of gluten in the diet, respectively. In some circumstances, it is very difficult to distinguish between NCWS and celiac disease. The presence of positive celiac disease specific serum antibodies (anti-tissue transglutaminase (anti-tTG), and anti-endomysium (EmAs) antibodies) is of paramount importance to pose the diagnosis. However, it is well known that the frequency of a positive serology is dependent by the severity of the intestinal damage. Consequently, patients with less severe histology damage (Marsh 1) can have negative serum antibodies. Previous studies had demonstrated that EmAs are produced by the intestinal lymphocytes and previous data from our group showed that EmAs assay in the culture medium of the intestinal biopsies has higher diagnostic accuracy than serum EmAs in diagnosis. Therefore, the aims of our study are to evaluate the clinical-serologic-histology course of NCWS patients, showing positive EmAs assay in the culture medium of the duodenal biopsies at the time of the first evaluation, and the adherence to a gluten-free diet in NCWS patients after a previous full evaluation and a NCWS diagnosis based on double-blinded placebo-controlled (DBPC) challenge.
详细描述
Gluten is the most important protein component of some grains, notably wheat, rye, and barley, which are the basis for a variety of wheat-derived alimentary products consumed throughout the world (bread, pasta, pizza etc). However the "engineering" of gluten-containing grains created the conditions for human diseases related to gluten exposure. These forms of gluten intolerance represent a heterogeneous set of conditions, including celiac disease, wheat allergy and gluten sensitivity (GS), that, combined, seems to affect about 10% of the general population.
The immune responsiveness to wheat antigens represents a complex process, and its establishment and maintenance are not completely elucidated. The most frequent diseases caused by wheat ingestion are T cell-mediated disorders, i.e. celiac disease and IgE-mediated allergic reactions. However, besides celiac disease and wheat allergy, there are cases of gluten reactions in which neither autoimmune nor IgE-mediated allergic mechanisms are involved. These are generally defined as GS or Not-celiac wheat sensitivity (NCWS), because it is not known what component of the cereals causes the symptoms. Some subjects, who experience symptoms when eating gluten-containing products and show improvement when following a gluten-free diet (GFD) may have NCWS instead of celiac disease or wheat allergy. NCWS patients are unable to tolerate gluten and develop an adverse reaction when eating gluten, that, usually, and differently from celiac disease, does not lead to small intestinal damage. Gastrointestinal symptoms in NCWS patients may resemble those associated with celiac disease, but the overall clinical picture is generally less severe.
Typically, NCWS diagnosis is made by exclusion, and an elimination diet and an "open challenge" (i.e., the monitored reintroduction of gluten-containing foods) are most often used to evaluate whether health improves or worsen with the elimination or reintroduction of gluten in the diet, respectively.
The frequency of NCWS is however still unknown, even though some studies indicated that it is higher than that of celiac disease; consequently, it is very probable that this condition have been undiagnosed and under-diagnosed by the physicians for a long time. However, it is very difficult, in some circumstances, to distinguish between NCWS and celiac disease. In fact, NCWS patients can show an intestinal histology characterized by intra-epithelial lymphocytosis (Marsh 1), a finding considered compatible with a celiac disease diagnosis. In this difficult, possible, celiac disease diagnosis, the presence of positive specific serum antibodies (anti-tTG and EmAs) is of paramount importance to pose the diagnosis. However, it is well known that the frequency of a positive serology is dependent by the severity of the intestinal damage. Consequently, celiac disease patients with less severe histology damage (Marsh 1) can have negative serum antibodies. Previous studies had demonstrated that EmAs are produced by the intestinal lymphocytes and previous data from our group showed that EmAs assay in the culture medium of the intestinal biopsies has higher diagnostic accuracy than serum EmAs in celiac disease diagnosis.
Therefore, this study has one major aim: 1. Evaluation of the clinical-serologic-histology course of NCWS patients showing positive EmAs assay in the culture medium of the duodenal biopsies at the time of the first evaluation; and one secondary aim: 2. Evaluation of the adherence to a GFD in NCWS patients after a previous full evaluation and a NCWS diagnosis based on double-blinded placebo-controlled (DBPC) challenge.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients, both genders, with age between 18-65 years, that has been previously diagnosed as NCWS, according to a DBPC method
- •Patients testing negative for celiac disease ( anti-tTG and EMA negative, and with biopsy Marsh 0-1) and wheat allergy (serum specific igE for wheat negative)
- •Patients showed positive EmAs in the culture medium of the duodenal biopsies
排除标准
- •Subjects diagnosed with celiac disease (positive anti-tTG and/or EMA, and positive histology, with Marsh 2 or above)
- •Subjects diagnosed with wheat allergy (positive serum specific IgE for wheat)
- •Subjects with Type 1 Diabetes
- •Subjects with Inflammatory Bowel Diseases (Crohn's disease or ulcerative colitis)
- •Subjects with Helicobacter pylori infection and other gastrointestinal infection
- •Pregnancy
结局指标
主要结局
Changes in the intestinal histology of NCWS patients who tested positives for EmAs in the culture medium of the intestinal biopsies, at the time of the first evaluation.
时间窗: At baseline and after at least one year since the initial NCWS diagnosis was posed.
Intestinal histology re-evaluation after at least one year since the initial NCWS diagnosis was posed. Marsh classification will be adopted: change from baseline (1st evaluation) to 2nd evaluation. The above parameter will be evaluated taking into account whether the patients adhered or not to a wheat-free diet.
次要结局
- Serum AGA evaluation.(At baseline and after at least one year since the initial NCWS diagnosis was posed.)
- Serum anti-tTG antibodies evaluation.(At baseline and after at least one year since the initial NCWS diagnosis was posed.)
- Adherence to a wheat-free diet(At baseline and after at least one year since the initial NCWS diagnosis was posed.)
- Symptoms/signs evaluation.(At baseline and after at least one year since the initial NCWS diagnosis was posed.)
- Serum DPG antibodies evaluation.(At baseline and after at least one year since the initial NCWS diagnosis was posed.)
研究者
Pasquale Mansueto
Researcher
University of Palermo