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Celiac disease screening in southern and East Asia

Makharia GK

Dig Dis, 2015;33(2):167-174.
PMID: 25925919 DOI: 10.1159/000369537

Until 1970s, celiac disease (CD) was considered to be an uncommon disease except in Western Europe. The global epidemiology of CD continues to evolve with improvement in the diagnostic tests, simplification of the diagnostic criteria and increase in awareness about the disease. The Asian region is currently at the crossroads of the frontier of knowledge and awareness of CD. In many Asian nations, CD is still considered to be either nonexistent or very rare. A notable exception is India, where CD has been well recognized, especially in the northern part, and 2 population-based studies have revealed a prevalence of 0.3-1.04%. Initial reports from Malaysia, China, Japan and Singapore suggest the existence of CD in these countries. Furthermore, a meta-analysis of the predisposing factors predicts a high probability of occurrence of CD in fair numbers in China. There are no formal reports on CD from Malaysia, Indonesia, Korea, Taiwan and many other nations in this region. With the impending CD epidemic in Asia, there are many challenges. Some of the efforts which are required include determination of prevalence of CD across the region, spreading of awareness among physicians and patients, training of dieticians for proper counseling and supervision of patients, creation of gluten-free food infrastructure in the food supply and creation of patient advocacy organizations. Although the absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years/decades. It is thus appropriate that the medical community across Asia define the extent of the problem and get prepared to handle the impending CD epidemic.

Matched MeSH terms: Celiac Disease/diagnosis*; Celiac Disease/genetics; Celiac Disease/therapy
The clinical significance of immunoglobulin A deficiency

Latiff AH, Kerr MA

Ann. Clin. Biochem., 2007 Mar;44(Pt 2):131-9.
PMID: 17362578 DOI: 10.1258/000456307780117993

IgA deficiency is the most common primary immunoglobulin deficiency. The prevalence in Caucasians is around one in 500, whereas in some Asian populations it is very uncommon. Most individuals with IgA deficiency are clinically asymptomatic. Those with symptoms of immunodeficiency have predominantly sinopulmonary or gastrointestinal infections, which are more severe when associated with IgG2, IgG4 or specific antibody deficiency. IgA deficiency is believed to be one end of a spectrum of immunodeficiency with common variable immunodeficiency at the most severe end. Although primary IgA deficiency is the most commonly encountered form, secondary deficiencies due to drugs or viral infections are recognized. IgA deficiencies can be partial or transient. Primary IgA deficiency is caused by a defect of terminal lymphocyte differentiation, which leads to underproduction of serum and mucosal IgA; affected individuals have normal IgA genes. A number of non-immunoglobulin genes have been implicated in IgA deficiency. There have been many diseases reported in association with IgA deficiency, particularly autoimmune diseases. The most common association is with coeliac disease (CD), which has special significance since CD is usually diagnosed by detection of specific IgA antibodies that are obviously lacking in IgA deficiency. There is no specific treatment for patients with symptomatic IgA deficiency. Antibiotics are prescribed in those with acute infections. A significant proportion of IgA-deficient individuals are reported to have anti-IgA antibodies in their serum. Although blood or blood products given to IgA-deficient individuals can lead to severe, even fatal, transfusion reactions, such reactions are rare.

Matched MeSH terms: Celiac Disease/complications; Celiac Disease/immunology; Celiac Disease/metabolism
Fulltext Prevalence of serum celiac antibodies in a multiracial Asian population--a first study in the young Asian adult population of Malaysia

Yap TW, Chan WK, Leow AH, Azmi AN, Loke MF, Vadivelu J, et al.

PLoS One, 2015;10(3):e0121908.
PMID: 25799401 DOI: 10.1371/journal.pone.0121908

BACKGROUND: Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible persons. The prevalence of CD in Malaysia is unknown. We aim to determine the seroprevalence of CD antibodies and also investigate the correlation between H. pylori infection and CD in the young and healthy multiracial Malaysian population.
METHODS: Healthy young adult volunteers between the ages of 18-30 years were consecutively recruited from June 2012 to May 2014 at the University of Malaya Medical Centre (UMMC), Kuala Lumpur. Serum samples from all the participants were tested for anti-gliadin antibody immunoglobulin A/immunoglobulin G (IgA/IgG) and anti-tissue transglutaminase antibody (tTG) IgA/IgG. Samples positive for both anti-gliadin and anti-tTG were further validated for anti-human endomysial IgA antibodies (EmA). Serological diagnosis of CD was made when anti-gliadin, anti-tTG and anti-EmA were positive.
RESULTS: 562 qualified participants with mean age 24 ± 2.4 years old were recruited into our study. CD was found in 7 participants where most of them were asymptomatic and unaware of their CD status. The median of anti-gliadin and anti-tTG IgA/IgG value was 38.2 U/ml (interquartile range, 28.3-60.4 U/ml) and 49.2 U/ml (interquartile range, 41.1-65.9 U/ml), respectively. Seroprevalence of CD antibodies was 1.9% (6 out of 324) in female while only 0.4% (1 out of 238) in male. Seroprevalence among Malay was 0.8% (2 of 236), Chinese was 1.7% (3 of 177) and Indian was 1.3% (2 of 149). Overall, seroprevalence of CD antibodies in healthy asymptomatic adults in the Malaysian population was 1.25% (95% CI, 0.78%-1.72%). No significant relationship was discovered between CD and H. pylori infection.
CONCLUSIONS: The seroprevalence of CD antibodies in healthy young adults in the Malaysian population was 1.25% (1 in 100). CD is underdiagnosed and it could be a much greater problem in Malaysia than previously thought.

Matched MeSH terms: Celiac Disease/blood; Celiac Disease/immunology; Celiac Disease/microbiology*; Celiac Disease/epidemiology*
Fulltext Can Helminth Infection Reverse Microbial Dysbiosis?

Loke P, Lim YAL

Trends Parasitol, 2015 Nov;31(11):534-535.
PMID: 26604162 DOI: 10.1016/j.pt.2015.10.001

There is growing interest in treating inflammatory conditions with helminth infection. Recently, Loukas and colleagues have reported promising results from using experimental hookworm infection to reduce gluten sensitivity in celiac disease patients. Analysis of microbiota samples from the trial is contributing to our understanding of the complexity underlying helminth–microbiota–host relationships.

Matched MeSH terms: Celiac Disease/etiology*
Automated diagnosis of celiac disease by video capsule endoscopy using DAISY Descriptors

Vicnesh J, Wei JKE, Ciaccio EJ, Oh SL, Bhagat G, Lewis SK, et al.

J Med Syst, 2019 Apr 26;43(6):157.
PMID: 31028562 DOI: 10.1007/s10916-019-1285-6

Celiac disease is a genetically determined disorder of the small intestine, occurring due to an immune response to ingested gluten-containing food. The resulting damage to the small intestinal mucosa hampers nutrient absorption, and is characterized by diarrhea, abdominal pain, and a variety of extra-intestinal manifestations. Invasive and costly methods such as endoscopic biopsy are currently used to diagnose celiac disease. Detection of the disease by histopathologic analysis of biopsies can be challenging due to suboptimal sampling. Video capsule images were obtained from celiac patients and controls for comparison and classification. This study exploits the use of DAISY descriptors to project two-dimensional images onto one-dimensional vectors. Shannon entropy is then used to extract features, after which a particle swarm optimization algorithm coupled with normalization is employed to select the 30 best features for classification. Statistical measures of this paradigm were tabulated. The accuracy, positive predictive value, sensitivity and specificity obtained in distinguishing celiac versus control video capsule images were 89.82%, 89.17%, 94.35% and 83.20% respectively, using the 10-fold cross-validation technique. When employing manual methods rather than the automated means described in this study, technical limitations and inconclusive results may hamper diagnosis. Our findings suggest that the computer-aided detection system presented herein can render diagnostic information, and thus may provide clinicians with an important tool to validate a diagnosis of celiac disease.

Matched MeSH terms: Celiac Disease/diagnosis*; Celiac Disease/pathology
Fulltext Coeliac disease: immunogenicity studies of barley hordein and rye secalin-derived peptides

Wahab WA, Šuligoj T, Ellis J, Côrtez-Real B, Ciclitira PJ

Int J Exp Pathol, 2016 Aug;97(4):303-309.
PMID: 27659035 DOI: 10.1111/iep.12199

Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A ω-gliadin/C-hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T-cell lines obtained from CD small intestinal biopsies. We also sought to investigate the potential cross-reactivity of wheat gluten-sensitive T-cell lines with peptic-tryptic digested barley hordein (PTH) and rye secalin (PTS). Synthesised candidate peptides were deamidated with tissue transglutaminase (tTG). Gluten-sensitive T-cell lines were generated by culturing small intestinal biopsies from CD patients with peptic-tryptic gluten (PTG), PTH or PTS, along with autologous PBMCs for antigen presentation. The stimulation indices were determined by measuring the relative cellular proliferation via incorporation of (3) H-thymidine. The majority of T-cell lines reacted to the peptides studied. There was also cross-reactivity between wheat gluten-sensitive T-cell lines and the hordein, gliadin and secalin peptides. PTH, PTS, barley hordein and rye secalin-derived CD antigen-sensitive T-cell lines showed positive stimulation with PTG. ω-gliadin/C-hordein peptide and rye-derived peptide are immunogenic to gluten-sensitive T-cell lines and potentially present in wheat, rye and barley. Additional CD toxic peptides may be shared.

Matched MeSH terms: Celiac Disease/immunology*; Celiac Disease/pathology
Multiphasic disseminated encephalomyelitis followed by optic neuritis in a child with gluten sensitivity

Ching BH, Mohamed AR, Khoo TB, Ismail HI

Mult Scler, 2015 Aug;21(9):1209-11.
PMID: 26199345 DOI: 10.1177/1352458515593404

Multiphasic disseminated encephalomyelitis (MDEM) followed by optic neuritis (ON) has been described as a new entity in recent years. Gluten encephalopathy has also been recognized as a neurological manifestation of celiac disease. Accurate diagnosis of both is important due to the therapeutic implications. We report a girl presenting with recurrent encephalopathic polyfocal demyelinating episodes followed by optic neuritis, and a clinical history suggestive of gluten sensitivity. She had persistently high ESR, neutrophilia, and tested positive for anti-MOG (myelin oligodendrocyte glycoprotein) antibody. She responded well to methylprednisolone in each relapse, and achieved remission for a year after azathioprine was added.

Matched MeSH terms: Celiac Disease/complications*
Fulltext Detailed assessment of nutritional status and eating patterns in children with gastrointestinal diseases attending an outpatients clinic and contemporary healthy controls

Tsiountsioura M, Wong JE, Upton J, McIntyre K, Dimakou D, Buchanan E, et al.

Eur J Clin Nutr, 2014 Jun;68(6):700-6.
PMID: 24424079 DOI: 10.1038/ejcn.2013.286

BACKGROUND/OBJECTIVES: In the era of modern multidisciplinary clinical management, very little is known about the prevalence and presentation of malnutrition in children with gastrointestinal disorders (GastroD) particularly employing composite, global measures of nutritional status.
SUBJECTS/METHODS: Anthropometry, body composition, dietary intake, eating habits and grip strength were assessed with bedside methods in 168 patients from outpatient gastroenterology clinics (n, median (IQR) years; Crohn's disease (CD): n=53, 14.2 (11.6:15.4); ulcerative colitis (UC): n=27, 12.2 (10.7:14.2); coeliac disease: n=31, 9.3 (7.5:13.6); other GastroD: n=57, 9.8 (7.2:13.8)) and compared with 62 contemporary healthy controls (n, median (IQR): 9.8 (6.9:13.8)) and the results of the recent UK, National Diet and Nutritional Survey (NDNS).
RESULTS: Children with CD had lower BMI z-scores than controls (median (IQR): -0.3 (-0.9:0.4) vs 0.3 (-0.6:1.4); P=0.02) but only 2% were classified as thin (BMI z-score

Matched MeSH terms: Celiac Disease/complications
Fulltext Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W, et al.

Cancer Res, 2020 Sep 15;80(18):4004-4013.
PMID: 32641412 DOI: 10.1158/0008-5472.CAN-20-0447

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

Matched MeSH terms: Celiac Disease/genetics
Fulltext The Human Gut Microbiome - A Potential Controller of Wellness and Disease

Kho ZY, Lal SK

Front Microbiol, 2018;9:1835.
PMID: 30154767 DOI: 10.3389/fmicb.2018.01835

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.

Matched MeSH terms: Celiac Disease
Iron deficiency in the tropics

Fleming AF

Clin Haematol, 1982 Jun;11(2):365-88.
PMID: 7042157
Matched MeSH terms: Celiac Disease/blood
Current trends in morbidity and mortality of children in Malaysia

Lin, Hai Peng, Mohd Sham Kasim

Malaysian Journal of Child Health, 1997;9(2):104-132.
MyJurnal

Malaysia is a rapidly developing country with a very young population, about 36% of which are below the age of 15 years. The standard of child health has improved greatly. However, there are great changes in the morbidity and mortality patterns of childhood diseases relating mainly to an improved standard of living; availability of safe water supply and adequate sanitary latrines; a higher literacy rate; rapid industrialisation and urban migration. The infant mortality rate has droppedfrom 50.1 per 1,000 livebirths in 1986 to 10.4 in 1995, and similar trends apply also to neonatal, perinatal and toddler mortality rates. Nevertheless, current major child health problems are those relating to events in the perinatal period and to infections. Despite improvements in the standard of neonatal care with the use ofhigh technology, the commonest cause of certified deaths still occur in the neonatal period. A rapid and inexpensive screening test for G6PD deficiency, a disease present in 2-3% of the population, is now widely available and, together with the use of phototherapy is largely responsible for the declining incidence of kernicterus in the country. Infections remain an important cause of morbidity and mortality although their patterns have changed. The very high (>95%) WHO-EPI-vaccines coverage rate is linked to the great reduction in the incidence of diphtheria, pertussis, tetanus, poliomyelitis and measles. Childhood tuberculosis is less common now, with about 250 - 300 reported cases per year and TB meningitis is rare with about 30-40 reported cases/year. The hepatitis B carrier rate is high (5%) and the introduction of routine newborn hepatitis B vaccination in 1989 is expected to have a positive impact as is the immunisation of young girls against rubella introduced in 1985 in reducing the incidence of congenital rubella syndrome. The incidence of malaria has declined but remains prevalent in the interiors of PeninsularMalaysia and in Sabah and Sarawak. Filariasis is largely under control. Unfortunately, despite great efforts at mosquito control, dengue virus infection remains a major problem with thousands of cases reported every year. Children are most susceptible to dengue haemorrhagic fever with many dying from the shock syndrome. The incidence of acute gastroenteritis has also dropped with most cases being due to a viral aetiology. Acute respiratory infections, mostly viral in origin, account for most attendances at paediatric outpatient services. Although staphylococcal and streptococcal impetigo and pneumonia are common, the incidence of streptococcal related diseases like rheumatic fever and acute glomendonephritis is rapidly declining. The nutritional status of children has improved in tandem with the rise in the standard of living, but subclinical malnutrition is prevalent, particularly among urban squatters and the rural poor. There is a disturbing decline in breastfeeding among urban working mothers. Poor weaning practices and food habits are responsible for the common occurrence of nutritional anaemia (5%) among infants and young children. Greater prosperity, rapid industrialisation and urbanisation have resulted in changes in the childhood disease pattern where non-communicable diseases assume greater importance as the problems of malnutrition and infection are gradually overcome. Road traffic accidents are a major killer and home accidents, largely preventable, are an important cause of morbidity and mortality. Childhood cancer, with about 550 new cases a year, is an important cause of death beyond infancy. Major congenital malformations, with a 1% prevalence rate, cause much ill-health. Thalassaemia is a particularly common genetic disease with fl thalassaemia gene frequency of about 5%. The prevalence of asthma is increasing, with a rate of 13.9% in the Kiang Valley but the prevalence of asthma-related symptoms is much higher. Physical, sexual child abuse and neglect, abandoned babies, substance abuse are but signs of stress of modern city living and peoples inability to cope with it. Although the general standard of child health has greatly improved, there are several states where it is still not satisfactory. In Sabah where there is a large illegal immigrant population, the infant mortality and infection rates are relatively high. In Kelantan and Trengganu, it is common for parents to refuse permission for a lumbar puncture required to treat meningitis. Other still deeply entrenched, culturally-related adverse health practices include : a fatalistic attitude to illness; a preference for traditional practitioners of medicine resulting in late treatment; and 'doctor-hopping' with unrealistic expectations of 'instant cure'. Childhood illnesses that are uncommon in Malaysia include: cystic fibrosis, coeliac disease, ulcerative colitis, Crohns disease, Sudden Infant Death Syndrome, Encopresis, enuresis and epiglottitis due to Haemophilus Influen:ae.

Matched MeSH terms: Celiac Disease

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