Search

Celiac disease (CD) follows an autoimmune course in which both genetic and environmental factors contribute to its development. A strong association with HLA class II molecules, predominantly HLA-DQ2, has been reported in most ethnic groups with CD. The aim of this study was to determine if genetic polymorphisms in L-selectin, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) have any correlation with CD. We investigated 5 mutations, namely F206L in L-selectin, S128R and L554F in E-selectin, and G241R and K469E in ICAM-1, in 37 North Indian pediatric patients with CD. A significant increase in allele frequencies of 128R of E-selectin and the associated genotype SR was observed in patients. No significant differences were observed in the F206L polymorphism of L-selectin, or the G241R and E469K polymorphisms in the ICAM-1 gene in CD. This study illustrates that selectin gene polymorphism might contribute to the genetic background of CD and invites further investigation relevant to understanding the mechanisms underlying the immunopathogenesis of this autoimmune disease.

The role of human leukocyte antigen (HLA) DQ2 heterodimer (DQA1*0501-DQB1*0201) in presenting gluten peptides to effector T cells in celiac disease (CD) has been well documented. Because HLA-DQ2 is carried on DR3 haplotypes due to linkage disequilibrium, such haplotypes are encountered more frequently in patients with autoimmune disease. This study analyzed 35 North Indian children below 15 years of age and diagnosed to have CD as per the ESPGAN criteria, which included histopathologic alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of antiendomysial antibodies. The HLA class I and class II alleles were determined by polymerase chain reaction-sequence-specific primers, sequence-specific oligonucleotide probe, and reverse line strip molecular techniques. A statistically significant positive association of the disease with HLA-DRB1*03 (94.2% versus 22.1% in controls, chi(2) = 73.4, p = 7.54E-11), and a negative association with DRB1*15 (chi(2) = 7.4, p = 6.5E-03) and DRB1*13 alleles was observed. The HLA-DQB1*0201 was observed in all the 35 patients (100%), whereas the DQ2 heterodimer alpha(0)beta(0) occurred in 97.1% of CD patients (31.4% in double dose, 65.7% in single dose) and revealed significant deviation from healthy controls (chi(2) = 102.08, p = 7.56E-11). Further analysis revealed involvement of multiple DR3+ve haplotypes with CD in Indians, of which A26-B8-DR3 was the most common DR3 haplotype among patients (34.28%, chi(2) = 40.57, p = 2.65E-10) followed by Ax-B21-DR3 (11.4%) (chi(2) = 13.8, p = 2E-04) and the classical Caucasian haplotype A1-B8-DR3 (5.7%). The former two haplotypes are characteristic of Asian Indians and are involved in the development of CD. We conclude that the high risk DR3 haplotypes that play a crucial role in the development of CD are unique in Asian Indians. Detailed analysis of these haplotypes in Indian patients with autoimmune diseases may help understand the influence of other intervening genes within the major histocompatibility complex.

In developing countries like India, unlike in the West, diagnosis of celiac disease is a dilemma because the histological changes consistent with celiac disease may not be pathognomonic of the disease. We need clarity on how to use one or more of the serological antibodies, namely IgG and IgA anti-gliadin and IgA anti-endomysial antibodies as independent disease markers or as adjuncts to clinico-histological diagnosis. In this review, various possible algorithms have been discussed. The serological antibodies can be used as reliable screening tests to decide whom to biopsy and to interpret histological changes in our settings where malnutrition and intercurrent enteric infection are common.

Serum anti-gliadin antibody (AGA) titres were estimated by diffusion in a gel enzyme-linked immunosorbent assay in children with coeliac disease (n = 11), protracted diarrhoea of non-coeliac causes (n = 110), acute gastroenteritis (n = 20), protein energy malnutrition (n = 20), and asymptomatic, well-nourished children (n = 66). The mean IgG and IgA AGA titres were significantly higher (p less than 0.001) in children with coeliac disease than in any other groups. There was no significant difference (p greater than 0.01) in AGA titres in relation to age, nutritional status, or severity of villous injury. In patients with coeliac disease AGA titres showed a good correlation with disease activity. The specificity and sensitivity of the assay are discussed.

R-1 anti-reticulin antibodies (ARA) were present in sera of 10 of the 12 children who subsequently fulfilled the ESPGAN diagnostic criteria for celiac disease (CD), but was not found in any children in the age-matched control groups, viz., severely malnourished (n = 20), acute gastroenteritis (n = 23), normally nourished asymptomatic (n = 38), and 42 children with protracted diarrhoea and failure to thrive due to nonceliac causes. ARA was a highly specific (100%) and sensitive (83%) assay for the early diagnosis of CD. A positive ARA assay with an initial subtotal villous atrophy was seen to always suggest CD, and these together would provide a useful basis for instituting gluten-free diets in suspected cases of CD rather than histological findings alone, which may be often present in children in the third world with protracted diarrhoea and associated severe malnutrition.