Celiac disease: quantity matters.
Celiac disease: quantity matters.
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DOI：
10.1007/s00281-012-0321-0
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发表时间：
2012-07
影响因子：
9
通讯作者：
Koning, Frits
中科院分区：
文献类型：
--
作者：
Koning, Frits
乳糜泻(CD)是由小麦和相关谷物中对面筋蛋白的免疫反应失控引起的。面筋是醇溶蛋白和谷蛋白的复杂混合物，大多数现代小麦品种含有多达100种高度相关但不同的面筋蛋白。这些醇溶蛋白和麦谷蛋白总是含有免疫原肽，特别是在这些肽被组织转谷氨酰胺酶(TG2)修饰后。这种修饰导致谷氨酰胺残基在面筋多肽中转化为带负电荷的谷氨酸。这会产生与疾病易感的HLA-DQ2.5或-DQ8分子强烈结合的多肽，这有助于诱导诱发疾病的CD4T细胞反应，这是CD的一个标志。众所周知，人类白细胞抗原-DQ基因决定了疾病发生的风险。此外，面筋蛋白中免疫原肽的丰富可能与观察到CD患者中经常发现多克隆T细胞对多种面筋多肽的反应有关。然而，并不是所有的患者对相同的一组多肽都有反应。在这里，我提出一个模型，整合这些观察结果，并将它们与CD相关的高度可变的临床症状谱联系起来。此外，我还讨论了改变小麦和/或面筋以使其适合CD患者食用的可行性。
Celiac disease (CD) is caused by uncontrolled immune responses to the gluten proteins in wheat and related cereals. Gluten is a complex mixture of gliadin and glutenin proteins and most modern wheat varieties contain up to 100 highly related, but distinct gluten proteins. Invariably, these gliadin and glutenin proteins contain immunogenic peptides, particularly so after the peptides have been modified by the enzyme tissue transglutaminase (TG2). This modification results in the conversion of glutamine residues in the gluten peptides into the negatively charged glutamic acid. This generates peptides that bind strongly to the disease predisposing HLA-DQ2.5 or -DQ8 molecules and this facilitates the induction of disease-inducing CD4 T cell responses, a hallmark of CD. It is well-known that the HLA-DQ genotype determines the risk of disease development. Moreover, the abundance of immunogenic peptides in the gluten proteins is likely linked to the observation that polyclonal T cell responses to multiple gluten peptides are usually found in patients with CD. However, not all patients respond to the same set of peptides. Here, I propose a model that integrates these observations and links them to the highly variable clinical spectrum of symptoms that are associated with CD. Moreover, I discuss whether it is feasible to alter wheat and/or gluten to make it suitable for consumption by CD patients.
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影响因子：
15.3
作者：
Arentz-Hansen, H;Korner, R;Molberg, O;Quarsten, H;Vader, W;Kooy, Y M;Lundin, K E;Koning, F;Roepstorff, P;Sollid, L M;McAdam, S N
通讯作者：
McAdam, S N
影响因子：
24.5
作者：
Mitea, C.;Havenaar, R.;Koning, F.
通讯作者：
Koning, F.
影响因子：
29.4
作者：
Gianfrani, Carmen;Siciliano, Rosa A.;Rossi, Mauro
通讯作者：
Rossi, Mauro
影响因子：
56.9
作者：
Shan, L;Molberg, O;Khosla, C
通讯作者：
Khosla, C
DOI：
10.1073/pnas.0306885101
发表时间：
2004-03-23
影响因子：
11.1
作者：
Kim, CY;Quarsten, H;Sollid, LM
通讯作者：
Sollid, LM