Celiac Disease: Presentation of 109 Children

Purpose

The clinical features of patients with celiac disease (CD) are variable. In the present study, clinical and laboratory features of 109 patients with CD were retrospectively evaluated.

Materials and Methods

In all cases, diagnosis of CD was made by European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria and clinical and laboratory findings, including hematological and biochemical analyses, immunoglobulin levels, autoantibodies [antinucler antibody (ANA), antidouble stranded DNA (dsDNA), antimitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA), liver kidney antibody (LKM-1), anti thyroid peroxidase (TPO), anti thyroglobulin (Tg)], bone mineral density (BMD), and electroencephalogram were evaluated. The type of CD was recorded.

Results

Of 109 patients with CD, 66 (60.6%) were classical type, 41 (37.6%) were atypical type and 2 (1.8%) were silent type. The mean age was 8.81 ± 4.63 years and the most common symptom was diarrhea (53.2%) followed by failure to thrive, short stature, and abdominal pain. Paleness (40.4%), underweight (34.8%), and short stature (31.2%) were the most common findings. Iron deficinecy anemia (81.6%), zinc deficiency (64.1%), prolonged prothrombin time (35.8%), and elevated transaminase levels (24.7%) were the most common laboratory findings. Eight percent of patients had at least 1 autoantibody, and 28 of 52 patients had low BMD. Four of 38 patients had abnormalty in electroencephalograms. The prevalance of selective immunoglobulin (Ig) A deficiency was 9.1%. Histocompatibility antigen HLA-DQ and/or DQ8 genotypes were found in 91% of patients. Abdominal distention, iron deficiency, prolonged prothrombine time, hypoalbuminemia, and elevated transaminase levels were more significantly frequent in the classical type than atypical type (p < 0.005).

Conclusion

Although classical CD was seen in most patients in the present study, clinical variability of the condition should be kept in mind.     

Serological Responses to Microbial Antigens in Celiac Disease Patients During a Gluten-Free Diet

Background  Immunoglobulin A (IgA) autoantibodies to tissue transglutaminase (tTG) are commonly used for screening and diagnosing of celiac disease (CD). Seroreactivity for anti-Saccharomyces cerevisiae antibody (ASCA) and bacterial antigens have also been detected in CD patients. The aim of this study was to examine prospectively serologic responses to microbial targets in adult CD patients at the time of diagnosis and during a gluten-free diet (GFD). Further, we wanted to evaluate whether these serologic specificities could provide new tools for the follow-up of CD patients. Methods  Data on 55 adult biopsy-proven CD patients were available for follow-up study. Upper gastrointestinal endoscopy was performed on all patients. Sera from patients were tested for antibodies to tTG and ASCA and additionally analyzed with IgA enzyme-linked immunosorbent assays to Pseudomonas fluorescens-associated sequence, I2, and to a Bacteroides caccae TonB-linked outer membrane protein, OmpW. Results  At the time of diagnosis, 91% of CD cases were positive for tTG and 49% for ASCA; positive seroreactivity to I2 was found in 86% and to OmpW in 60% of CD patients at the time of diagnosis. The frequency of seropositivity and serum levels of these antibodies decreased during GFD. Moreover, we found that the decline in the serum levels was significant in all of these markers (p < 0.005). Interestingly, we also found that serum levels of ASCA correlated with the grade of mucosal morphology (p = 0.021), as the ASCA serum levels declined in accordance with mucosal healing. Conclusions  Commensal enteric bacteria seem to play a role in the small intestinal mucosal damage in CD. This was proven by the serological responses to different microbial antigens shown in this study. Serum levels of ASCA, anti-I2, and anti-OmpW antibodies decreased significantly during GFD, indicating that these serologic markers are gluten dependent in CD patients. These specificities could provide new tools in the follow-up of CD patients.     

Autoantibody Frequency in Celiac Disease

AIM:

In our study, we investigated the levels of glutamic acid decarboxylase antibody (anti-GAD), islet cell antibody (ICA), thyroperoxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), antinuclear antibodies (FANA), antibodies to double-stranded DNA (anti-ds DNA), antibody to Sjögren syndrome A antigen (anti-SSA), antibody to Sjögren syndrome B antigen (anti-SSB), Smith antibody (anti-Sm), smooth muscle antibodies (ASMA), and antimitochondrial antibody liver-kidney microsome (AMA-LKM) in patients with celiac disease as compared to healthy controls and autoimmune hypothyroid patients.

MATERIALS AND METHODS:

A total of 31 patients with celiac disease, 34 patients with autoimmune hypothyroidism and 29 healthy subjects were included in this study. Anti-SSA, anti-SSB, anti-Sm, anti-ds DNA, anti-GAD, anti-TPO and anti-TG were studied by Enzyme-Linked Immunosorbent Assay (ELISA), and AMA-LKM, ASMA, ANA and ICA were studied by immunofluorescence. Clinical data and the results of free thyroxine-thyroid stimulating hormone (FT4-TSH) were collected from the patients’ files by retrospective analysis. SPSS ver 13.0 was used for data analysis, and the χ² method was used for comparisons within groups.

RESULTS:

The frequency of anti-SSA, anti-SSB, anti-GAD, anti-Sm, anti-ds DNA, AMA-LKM, ASMA, ANA and ICA were not significantly different between the groups. Levels of anti-TPO and anti-TG antibodies were found to be significantly higher (<0.001) in autoimmune hypothyroid patients when compared with other groups.

CONCLUSION:

In previous studies, an increased frequency of autoimmune diseases of other systems has been reported in patients with celiac disease. We found that the frequency of autoimmune antibodies specific for other autoimmune diseases was not higher in celiac disease.     

Pathogenesis and Clinical Significance of Liver Injury in Celiac Disease

Abnormalities of liver function are one of the manifold extraintestinal manifestations of celiac disease. Although the spectrum of liver manifestations associated with celiac disease is particularly wide, two main forms of liver damage namely, cryptogenic and autoimmune, appear to be strictly related to gluten-sensitive enteropathy. The most frequent finding is represented by a cryptogenic hypertransaminasemia, observed in about a half of untreated celiac patients, as an expression of a mild liver dysfunction with a histological picture of nonspecific reactive hepatitis (celiac hepatitis) reverting to normal after 6–12 months of a strict gluten-free diet. In a few cases, when celiac disease is diagnosed, a more severe liver injury, characterized by a cryptogenic chronic hepatitis or liver cirrhosis, is present. In these patients, liver damage can still improve after a gluten-free diet institution. Moreover, a close association between celiac disease and autoimmune liver disorders has been widely demonstrated. Indeed, celiac disease has been found in 3–7% of patients with primary biliary cirrhosis, in 3–6% with autoimmune hepatitis, and in 2–3% with primary sclerosing cholangitis. Differently from cryptogenic liver injury, autoimmune liver dysfunction, found in celiac disease, does not usually improve after a gluten-free diet. Presently, it is difficult to establish if the two main kinds of liver injury found in celiac disease (cryptogenic and autoimmune) are discrete entities with a different pathogenesis or if they are an expression of the same disorder where genetic factors and the duration of gluten exposure may determine the severity and the pattern of liver injury.     

先天性心脏病患儿的全血粘弹特性

本文采用Low Shear-30流变测定仪,测定了52例青紫型先天性心脏病(CCHD)患儿,51例非青紫型先天性心脏病(ACHD)患儿)以及CCHD组中3例有严重并发症患儿的全血粘弹性参数。按年龄和性别分别与相应对照组比较。结果表明:(1)CCHD组的Hb、RBC、HCT、η_(0.512)、η_(5.96)、η_(51.2)、η、η″G、AI明显增高;OD明显降低,而Fib、ηp则无明显变化。(2)ACHD组仅有Hb、OD明显增高,其余全血粘弹性参数无明显变化。(3)3例有严重并发症的CCHD患儿的全血粘弹参数,除ηp、Fib、OD明显降低外,其余指标均明显增高。其升高幅度明显大于无并发症的CCHD患儿。本文所提出的CCHD并发症患儿全血粘弹性参数变化的临界值,可为临床早期诊断和防治并发症提供参考资料。     

Important Lessons Derived from Animal Models of Celiac Disease

Several animal models have been recently developed to recapitulate various components of the complex process that is celiac disease. In addition to the increasing diversity of murine models there are now monkey models of celiac disease. Mouse strains and protocols have been developed that are now just beginning to address the complex interactions among the innate and adaptive immune responses to gluten, as well as gluten-dependent autoimmunity in celiac disease. The most important conclusion that these models have provided us with so far is that while all three components (innate gluten sensitivity, adaptive gluten sensitivity, and autoimmunity) are independent phenomena, all are necessary for celiac disease to develop.     

Celiac disease in Tunisia: serological screening in healthy blood donors

BACKGROUND: Recent epidemiological studies in Europe and in USA using antigliadin antibodies and antiendomysium antibodies for initial screening have shown that the overall prevalence of celiac disease (CD) is about 1:200 (0.5%). AIM: To screen for CD in healthy blood donors in Tunisia. PATIENTS AND METHODS: Sera from 2500 healthy blood donors (median age: 21 years, 70% men and 30% women) were screened for IgG-antigliadin antibodies and IgA-antigliadin antibodies with an enzyme-linked immunosorbent assay. All sera with positive antigliadin antibodies were tested for antiendomysium antibodies using human umbilical cord cryosections as substrate. RESULTS: Seven healthy blood donors (median age: 21 years; four men, three women) have antiendomysium antibodies. The prevalence of antiendomysium antibodies in healthy blood donors in Tunisia is 1:355 (0.28%). CONCLUSIONS: On the basis of a high specificity of the antiendomysium antibodies, it is likely that the seven blood donors identified in this study have CD. These data suggest that CD is frequent in Tunisia.     

Isolation of Non-Activated Monocytes from Human Umbilical Cord Blood

Problem  Methods for monocyte purification are common but few work with umbilical cord monocytes that do not activate the cell for subsequent culture analysis.
Methods of study  The collection procedure avoids use of needles and procedures that variably activate blood clotting and uses a purification procedure that involves diluted Ficoll, autologous serum to remove platelets and 42% and 51% Percoll step gradients for the final purification. The resulting monocytes were stimulated with bacterial lipopolysaccharide and formalin-treated bacteria Escherichia coli and group B streptococci (GBS) to secrete TNF-α and IL-1β, measured by ELISA.
Results  The purification procedure results in non-active but stimulation-competent monocytes with high yields (2.3–9 × 10⁷ cells) and purity (from 70% to 98%).
Conclusion  We describe a procedure that is easy, uses common reagents and provides a uniformly high yield and purity of non-activated fetal monocytes for studies of innate defense responses.     

miR-144 在慢性阻塞性肺疾病患者外周血血清和单核细胞中的表达及其临床意义

目的 探究 miR-144 在慢性阻塞性肺疾病 ( chronic obstructive pulmonary disease, COPD) 患者外 周血血清和单核细胞中的表达及其临床意义。 方法 选取 2020 年 3 月至 2021 年 6 月内江市第二人民医院 收治的 58 例 COPD 稳定期患者为观察组, 另选取同期 45 例健康体检者为对照组。 收集所有患者的一般临 床资料。 采用实时荧光定量 PCR 法 (qRT-PCR) 检测所有患者外周血血清和单核细胞中 miR-144 的表达水 平。 分析 COPD 患者外周血血清及单核细胞中 miR-144 表达水平与肺功能的关系。 Pearson 相关性分析 COPD 患者外周血血清及单核细胞 miR-144 表达水平与一秒用力呼气容积 ( forced expiratory volume in first second, FEV1) 的相关关系。 ROC 曲线分析患者外周血血清和单核细胞 miR-144 水平对 COPD 的诊断价值。 结果 与对照组相比, COPD 患者外周血血清及单核细胞中 miR-144 的表达水平均明显升高, 其差异具有 统计学意义 (P< 0. 05)。 COPD 患者外周血血清及单核细胞中 miR-144 的表达水平均随着肺功能严重程度 的加重而依次升高, 其差异具有统计学意义 (P< 0. 05)。 Pearson 相关性分析结果显示, COPD 患者外周血 血清及单核细胞 miR-144 表达水平与 FEV1 均呈负相关关系 (r = - 0. 517, r = - 0. 463, P< 0. 05)。 ROC 曲 线分析结果显示, 外周血血清和单核细胞 miR-144 水平对 COPD 诊断价值的 ROC 曲线下面积 (AUC) 分别 为 0. 857、 0. 849, 截断值为 1. 371、 1. 890, 敏感度为 84. 50 % 、 84. 50 % , 特异性为 80. 00 % 、 88. 90 % 。 结论 COPD 患者外周血血清和单核细胞 miR-144 水平显著上调, 且参与调节疾病的发展程度, 对发生 COPD 具有一定的诊断价值。     

Mast Cells and Innate Cytokines are Associated with Susceptibility to Autoimmune Heart Disease Following Coxsackievirus B3 Infection

The development of autoimmune disease involves a combination of genetic and environmental factors. Many autoimmune diseases are believed to be triggered by viral infections. Since the early, natural immune response to infection can determine the later development of the adaptive immune response, innate immunity likely influences the progression from viral immunity to autoimmunity. To investigate the role of the innate immune response on susceptibility to autoimmune disease, we compared the early cytokine response of mice susceptible or resistant to the development of autoimmune heart disease following viral infection. We found that susceptible BALB/c mice produced elevated levels of TNF-α, IL-1β, and IL-4 within hours of Coxsackievirus B3 (CB3) infection. These cytokines are known to be critical for the development of autoimmune heart disease, and are also rapidly produced from activated mast cells (MC). Degranulating MC were observed as early as 6?h following CB3 infection in the heart, and significantly higher numbers of MC were found in the spleen of susceptible BALB/c mice at this time. Thus, susceptibility to autoimmune heart disease can be determined as early as 6?h following viral infection in susceptible strains of mice.     

Celiac disease-specific and inflammatory bowel disease-related antibodies in patients with recurrent aphthous stomatitis

The etiology of recurrent aphthous stomatitis (RAS) remains unknown. RAS can be presented as primary, idiopathic condition and as a secondary RAS, which is associated with a systemic disease. The aim of our study was to evaluate the presence and concentrations of antibodies specific for celiac disease (CeD) and antibodies related to inflammatory bowel diseases (IBD) in patients with RAS without gastrointestinal symptoms. Antibodies against tissue transglutaminase (anti-tTG), deaminated gliadin peptides (DGP), deaminated gliadin-analogous fragments (anti-GAF-3X) and Saccharomyces cerevisiae (ASCA) were determined by ELISA and antineutrophil cytoplasmic antibodies (ANCA) by indirect immunoflurescence (IIF) in 57 patients with RAS and 60 control subjects. The prevalence of CeD specific antibodies did not differ between RAS patients and controls. However, the concentrations of IgA anti-tTG, IgA anti-GAF-3X antibodies in patients with RAS were significantly higher compared to controls (p?=?0.002 and p?=?0.04 respectively). Histological changes consistent with CeD were confirmed by duodenal biopsy in one RAS patient with highly positive IgA anti-tTG, anti-GAF-3X and anti-DGP antibodies. Higher prevalence along with higher concentrations of IgG ASCA were found in RAS patients compared to controls (p?<?0.01). Patients with positive IgG ASCA in the absence of clinical symptoms decided not to pursue any further testing. Dysfunction of oral mucosa and the exposure to various antigens might be a reason for the loss of tolerance resulting in increased production of autoantibodies. It seems likely that antibodies are markers of aberrant immune response, rather than key effectors involved in the pathogenesis of the disease.     

血液透析联合血液灌流在终末期肾病患者治疗中的应用

目的 探究血液透析联合血液灌流在终末期肾病患者治疗中的应用效果。方法 选取我院2016年1月~2018年12月治疗的终末期肾病患者94例,其中47例接受血液透析治疗,为对照组;另外47例接受血液透析联合血液灌流治疗,为试验组。比较两组治疗前后的血清β2微球蛋白（β2-MG）、甲状旁腺激素（PTH）、血肌酐（Scr）、尿素氮（BUN）和临床疗效。结果 试验组β2-MG、PTH、Scr和BUN水平分别为（2.94±0.52）mg/L、（251.64±20.42）pg/L、（532.69±114.31）μmol/L和（10.58±2.68）mmol/L,均低于对照组的［（4.89±0.64）mg/L、（270.83±22.45）pg/L、（580.25±118.57）μmol/L和（13.44±3.59）mmol/L］,差异有统计学意义（P＜0.05）。试验组治疗总有效率高于对照组（93.62% vs 78.72%）,差异有统计学意义（P＜0.05）。结论 对终末期肾病患者采用血液透析联合血液灌流治疗,有利于改善患者的各项生理指标,提高临床疗效。     

冠心病患者血液粘度与HDL-C和HDL-C/TC的变化及其关系

本文观察了79例CHD患者和125例中老年对照者血液粘度中的ηb低切、ηb高切和ηP以及血脂中的HDL－C和HDL－C／TC。结果表明CHD患者血液粘度呈高粘滞状态，血脂呈低HDL－C状态；对照组仅HDL－C与ηb低切有较好的负相关，而CHD组的HDL－C和HDL－C／TC与ηb低切和ηb高切均有良好的负相关。结果提示在临床上同时检测这些指标并观察其负相关关系，对协助诊断CHD和预测心血管危险因子具有更大价值。     

Analysis of the Expression of MICA in Small Intestinal Mucosa of Patients with Celiac Disease

The MHC class I chain-related A gene (MICA) is expressed in gastrointestinal epithelium and functions as an immune activation signal under stress conditions. MICA protein binds to NKG2D, a receptor of gamma delta T cells containing the TCR variable region V(delta)1, which are the most abundant subset of T cells in the intestinal epithelium. Ingested gluten in patients with celiac disease (CD) may function as a stress signal for the epithelial cells, and could enhance MICA expression on their surface. In this study, we have analyzed MICA expression in intestinal biopsy specimens from newly diagnosed and treated CD patients and controls. Quantitative RT-PCR analysis did not show differences in MICA expression among the three groups. With these results, we conclude that overexpression of MICA does not seem to play an important role in the pathogenesis of CD, at least at the time of diagnosis.     

Innate immunity is a late event in the onset of gliadin-specific enteropathy in the HLA-DQ8 mice

Celiac disease (CD) is a food enteropathy that occurs in genetically susceptible individuals following the ingestion of gluten. Both gluten cytotoxicity and immunity activation play a role in CD pathogenesis; however, the chronological assessment of the different pathogenic mechanisms remains elusive. The models developed so far have only partially addressed this issue. Herein, Ab°DQ8 transgenic mice were administered wheat gliadin and indomethacin for 10 days to induce enteropathy. Gliadin-induced alteration of the small intestinal architecture was associated with increased expression of tissue transglutaminase in the lamina propria and a marked hypoxic environment. Enteropathic mice showed activation of innate immunity, featuring an increase of pro-inflammatory IFN-γ and IL-15 mRNAs, as well as CD11c⁺CD103⁺, CD11b⁺CD11c⁺, and CD11b⁺CD103⁺ dendritic cell subsets. However, the temporal assessment of examined parameters indicated that the induction of innate immunity during the generation of the mucosal lesion, occurred belatedly, highlighting a major role of gliadin intrinsic cytotoxicity in the pathogenic mechanism of this model. These results have important implications for the use of this model to test the impact of biotechnological interventions to reduce the cytotoxicity of gliadin.     

脑卒中病人的全血粘度与血液成份

３１例脑梗塞与３５例脑出血病人的全血粘度和血浆成份的测定结果表明，脑梗塞与脑出血病人的全血粘度、血球压积及纤维蛋白原含量都明显高于对照组，但在脑出血和脑梗塞病人之间却没有差异。血球压积和纤维蛋白原增高是脑卒中后的一种继发性改变。全血粘度增高不是引起脑卒中的原因，而是脑卒中的后果。     

老年冠心病患者血液流变学对比观察

本文就164例老年冠心病(CHD)患者血液流变学变化与100名健康老年人比较,发现老年CHD患者血液流变学改变是明显的,尤以全血低切粘度(?)20S~(-1)最为显著(t检验,P<0.002).从临床分型看,CHD越严重,血液流变学改变越明显.但隐匿型CHD患者与健康老年人的血液流变学指标比较,无明显差异.提示血液流变学检查不适用于CHD的早期诊断,但可以判断CHD的严重程度及其预后,对指导治疗及疗效观察有一定的参考价值.     

血脂异常与老年冠心病患者冠脉病变程度的相关性研究

目的 探讨血脂异常与老年冠心病患者冠脉病变程度的相关性。方法 选取2015年5月~2017年1月本院心内科住院的明确诊断为冠状动脉粥样硬化性心脏病（CHD）的150例老年患者设为CHD组。选取同期收治的150例非CHD患者为对照组。比较两组血清中总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平,并计算N-HDL-C、LDL-C/N-HDL-C、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C值。比较不同冠脉病变支数、不同病情严重程度的CHD患者的血脂及其比值。对血脂与冠脉病变支数、病情严重程度积分进行相关性分析。结果 CHD组患者LDL-C、TG、TC、N-HDL-C水平、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C值均高于对照组,HDL-C水平低于对照组,差异均有统计学意义（P＜0.05）;不同冠脉病变支数各亚组间的TC、TG、N-HDL-C水平、TC/HDL-C比值差异存在统计学意义（P＜0.05）;TC、TG、N-HDL-C水平、TC/HDL-C比值均与冠脉病变支数均呈正相关（P＜0.05）;不同病情严重程度亚组间的LDL-C、TC、TG、N-HDL-C水平、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C比值差异存在统计学意义（P＜0.05）;CHD患者LDL-C、TC、TG、N-HDL-C水平、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C比值与冠状动脉病变积分均呈正相关（P＜0.05）。结论 可以通过对血脂指标的监测,并计算N-HDL-C、TC/HDL-C、LDL-C/HDL-C、TC/HDL-C、TG/HDL-C值,来评估CHD病情的临床进展。     

血瘀型心脑血管疾病舌诊之初探

运用舌诊对５０例血瘀型心脑血管病患者进行研究，并与３１例健康者比较。发现：二组对比中，无论舌象异常与否，血瘀型患者的微循环障碍均极显著地高于对照组（Ｐ＜０．００１）。资料证明，血瘀证是与微循环障碍相联系的病理生理过程。但指出，相似年龄组有舌象异常，但无临床血瘀诸证，却显示出微循环障碍，此现象有待研究。