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36 COELIAC DISEASE IN THE SAHARAWI were instead 95.6% in comparison with 41.6% of the controls. Finally, all but one patient (98.6%) and 42.5% of the controls were found to be positive for the DQB1*0201 allele. The CD associations observed in the Saharawi population were then contrasted with 5 those observed in other populations . While the (DR3)DQA1*0501- DQB1*0201/(DR3) DQA1*0501-DQB1*0201 genotype seems to be strongly and GENOTYPES DQA1 DQB1 DQA1 DQB1 Patients Controls N N OR 95% C.I. P
COELIAC DISEASE IN THE SAHARAWI 37 confirmation of the reliability of the CD diagnosis (based on both the serum EMA testing and the small intestinal biopsy) in these North African children. Most importantly, these results are also clear evidence that CD has a similar HLA association in distantly related populations. The aetiological mechanism of the class II association involves binding and T cell recognition of gluten derived peptides deaminated in the 25 small intestine by the enzyme tissue transglutaminase , and these properties of class II molecules are very likely conserved among different ethnic groups. In a manner consistent with the high disease prevalence, the main CD susceptibility haplotype DQA1*0501-DQB1*0201, detected nearly always within a DR3 haplotype, exhibited one of the highest frequencies in the world in the general background Saharawi population. This could partially explain the very high CD prevalence observed in the Saharawi population. However, it should be noted that a similar frequency of DQA1*0501-DQB1*0201 has been found also in other populations, such 26 as the Sardinians where the disease is around 5 times less frequent (1%) . Our results therefore suggest that other non-DQ genes or environmental factors are also operative in determining the high CD prevalence observed in the Saharawi. From an evolutionary perspective, such disease frequency might be related to the high prevalence of genes such as the Dq2, that have been selectively neutral or even beneficial for several hundred generations, that became disadvantageous following quick and dramatic changes of the environmental context in which the Saharawis lived. In the traditional Saharawi diet, the intake of gluten was very low and its introduction usually occurred after the second or third year of life. During the last century, in a span of few generations, wheat-based products, especially bread, have become the staple food after the Spanish colonization. Nowadays, gluten is introduced early in the Saharawi infant's diet, occasionally as early as the first month of life. Since in CD the 27 degree of intestinal mucosal damage is related to the amount of ingested gluten , the enteropathy of the “ancestral” CD-prone individuals was presumably milder. As such, in terms of genetic fitness, it did not represent a major selective disadvantage or might have even exerted some protective effect against intestinal infections because a moderately atrophic jejunal mucosa partially lacks the membrane receptors required 28 for microorganisms adhesion . Moreover, a mild CD and the accompanying small degree of inflammation of the jejunal mucosa, can also provide a source of reactive lymphomonocytes, thus further increasing the protective effect against intestinal infections. In contrast, the severe celiac enteropathy currently found in Saharawi children is associated with an early and high gluten intake and it is no longer neutral or “protective” but instead harmful, as it causes early intestinal malabsorption and 29 malnutrition, potentially leading to death . From these data a more general theory can be proposed. High disease frequency of a complex trait in a given population might be related to the high prevalence of genes that have been selectively neutral or even beneficial for several hundred generations, but became disadvantageous following quick changes of the environment. According to this interpretation, complex traits can be regarded as “residual traits“ caused by dramatic transformations of the environmental context in which a given population used to live across evolutionary time periods. Some environmental transformations can occur too quickly to be accompanied by changes in the genetic structure of the human populations. Indeed, the evolutionary time periods necessary to modify the genetic
Page 1: Perspectives on Coeliac Disease Vol
Page 4: The AIC Meeting was held in the Aul
Page 8 and 9: Italian Coeliac Society, Via Picott
Page 11 and 12: Preface Coeliac disease (CD) is a u
Page 13: Contents Current understanding of t
Page 16 and 17: 2 THE BASIS OF COELIAC DISEASE hapl
Page 18 and 19: 4 THE BASIS OF COELIAC DISEASE 1 pr
Page 20 and 21: 6 THE BASIS OF COELIAC DISEASE spre
Page 22 and 23: 8 THE BASIS OF COELIAC DISEASE Ackn
Page 24 and 25: 10 THE BASIS OF COELIAC DISEASE glu
Page 27 and 28: Catassi C, Fasano A, Corazza GR (ed
Page 29: T CELL RESPONSES TO GLUTEN PEPTIDES
Page 32 and 33: 18 A DOMINANT EPITOPE IN GLUTEN PEP
Page 42 and 43: 28 ROLE OF A-GLIADIN 31-49 PEPTIDE
Page 47 and 48: COELIAC DISEASE IN THE SAHARAWI 33
Page 49: COELIAC DISEASE IN THE SAHARAWI 35
Page 53 and 54: COELIAC DISEASE IN THE SAHARAWI 39
Page 55: COELIAC DISEASE IN THE SAHARAWI 41
Page 58 and 59: 44 INFANT FEEDING PRACTICES AND COE
Page 66 and 67: Age (years) 52 INFANT FEEDING PRACT
Page 76 and 77: 62 MECHANISMS OF ORAL TOLERANCE the
Page 78 and 79: 64 MECHANISMS OF ORAL TOLERANCE pot
Page 80 and 81: 66 MECHANISMS OF ORAL TOLERANCE Epi
Page 82 and 83: 68 MECHANISMS OF ORAL TOLERANCE typ
Page 84 and 85: 70 MECHANISMS OF ORAL TOLERANCE 51
Page 86 and 87: 72 MECHANISMS OF ORAL TOLERANCE 23.
Page 91 and 92: GENETICALLY DETOXIFIED GRAINS 77 to
Page 93 and 94: • • GENETICALLY DETOXIFIED GRAI
Page 95 and 96: GENETICALLY DETOXIFIED GRAINS 81 3.
Page 99 and 100: IMMUNOTHERAPY OF COELIAC DISEASE 85
Page 101 and 102:
IMMUNOTHERAPY OF COELIAC DISEASE 87
Page 103 and 104:
Catassi C, Fasano A, Corazza GR (ed
Page 105 and 106:
RECENT ADVANCES ON GLUTEN TOXICITY
Page 107 and 108:
Index A Antiendomysium antibodies (
Page 109:
INDEX 95 W Wheat, 7, 23, 27, 31, 53
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