Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease.

Mäki, Markku; Holm, K; Collin, Pekka; Savilahti, Erkki

doi:10.1136/gut.32.11.1412

Cited by 170 publications

(86 citation statements)

References 23 publications

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“…These features include an increased number of intraepithelial lymphocytes (IELs) (with an overexpression of c/d Tcell receptor lymphocytes); the presence of IgA and IgM gliadin antibodies (AGA) in the intestinal juices; and the presence of serum IgA antiendomysial antibodies (EmA), usually at low titer (,1 : 40). 73,74 The potential form of the disease is considered the first step toward the flat mucosa characteristic of CD, and when the disease develops with the typical atrophy of small intestine mucosa, the condition is renamed 'latent CD'. Potential celiacs are frequently asymptomatic or may suffer from mild intestinal symptoms, such as abdominal pain, resembling those of irritable bowel syndrome.…”

Section: Introductionmentioning

confidence: 99%

Celiac disease: diagnostic criteria in progress

2011

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Until a few years ago, celiac disease (CD) was thought to be a rare food intolerance that was confined to childhood and characterized by severe malabsorption and flat intestinal mucosa. Currently, CD is regarded as an autoimmune disorder that is common in the general population (affecting 1 in 100 individuals), with possible onset at any age and with many possible presentations. The identification of CD is challenging because it can begin not only with diarrhea and weight loss but also with atypical gastrointestinal (constipation and recurrent abdominal pain) and extra-intestinal symptoms (anemia, raised transaminases, osteoporosis, recurrent miscarriages, aphthous stomatitis and associated autoimmune disorders), or it could be completely symptomless. Over the last 20 years, the diagnostic accuracy of serology for CD has progressively increased with the development of highly reliable tests, such as the detection of IgA tissue transglutaminase and antiendomysial and IgG antideamidated gliadin peptide antibodies. The routine use of antibody markers has allowed researchers to discover a very high number of 'borderline' cases, characterized by positive serology and mild intestinal lesions or normal small intestine architecture, which can be classified as potential CD. Therefore, it is evident that the 'old celiac disease' with flat mucosa is only a part of the spectrum of CD. It is possible that serology could identify CD in its early stages, before the appearance of severe intestinal damage. In cases with a positive serology but with mild or absent intestinal lesions, the detection of HLA-DQ2 and HLA-DQ8 can help reinforce or exclude the diagnosis of gluten sensitivity.

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Section: Introductionmentioning

confidence: 99%

Celiac disease: diagnostic criteria in progress

2011

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“…Increased numbers and an increased proportion of / relative to / IEL in the small intestinal mucosa are a hallmark of coeliac disease, whether disease is active or in remission [15][16][17]. In addition, healthy first degree relatives of coeliac disease patients have increased numbers of / IEL in the small intestinal mucosa, and this correlates with whether or not those subjects express the HLA class II coeliac disease susceptibility alleles [20].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, T cells that express the / form of the TCR are abundant in the lamina propria and intraepithelial region. In addition to active coeliac disease, patients with treated coeliac disease are reported to have an increased proportion of / IEL to / IEL, and this finding has been used as a diagnostic adjunct for latent coeliac disease [15][16][17][18][19]. Furthermore, increased numbers of mucosal / T cells have been noted in otherwise healthy, first degree relatives of coeliac disease patients who carry the disease-associated HLA class II susceptibility alleles [20].…”

Section: Introductionmentioning

confidence: 99%

Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Holtmeier

Rowell

Nyberg

et al. 1997

Clinical and Experimental Immunology

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SUMMARYOne of the hallmarks of coeliac disease, both active and treated, is an increased number and proportion of°/± intraepithelial T lymphocytes in the small intestinal mucosa, and an increased number of°/± T cells in the small intestinal mucosa of coeliac disease patients has been associated with the inheritance of specific HLA class II DQ alleles. Nonetheless, the contribution of genetic factors to the development of the T cell receptor (TCR) ± repertoire in coeliac disease is not known. We have assessed the contribution of genetic factors to development of the TCR ± repertoire in coeliac disease, by characterizing the junctional diversity of TCR ± transcripts expressed in the intestine and peripheral blood of a pair of monozygotic (MZ) twins concordant for coeliac disease. TCR V±1, V±2 and V±3 transcripts from small intestinal and colon biopsies, and from peripheral blood mononuclear cells, were amplified by polymerase chain reaction (PCR) and the complementarity determining region (CDR)3 domains of TCR ± transcripts were analysed by denaturing PAGE and direct nucleotide sequencing. The repertoire of TCR ± transcripts and CDR3 amino acid motifs in the intestine and peripheral blood of MZ twins concordant for coeliac disease exhibited no overlap. The TCR ± repertoire in each twin was oligoclonal, and complexity of the junctional regions of their TCR ± transcripts was typical of the repertoire in healthy adults. Thus, genetically identical individuals with coeliac disease have distinct, non-overlapping TCR ± repertoires. Moreover, genetic factors that determine disease susceptibility do not appear to select for specific TCR ± sequences or CDR3 amino acid motifs. Keywords ±T cell receptor coeliac disease monozygotic twins T cell receptor repertoire°/

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“…Moreover, there are reports of relatives of coeliac patients who have only an increased number of intraepithelial lymphocytes with negative antibodies, but who should also be considered potentials. [9].On the other hand, the same question regarding the sensitivity of coeliac antibodies in those CD cases without frank atrophy could be put the other way around: are minimal lesions seen on histology specific for CD? Such a question would make the discussion even more complex.…”

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confidence: 99%

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Histologic evidence for mild lesions in coeliac disease: the challenge is open

Biagi

2011

Intern Emerg Med

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Even though research on coeliac disease (CD) has already given us fundamental clinical and pathogenic clarifications, CD is a very complex disease that has not finished surprising us. In the last two decades, the attention of clinicians was focussed on the wide spectrum of clinical presentations of the disease. This has made it possible to diagnose many patients with minor and silent forms of CD, particularly in adulthood, patients who would not have received a diagnosis in the past [1]. In the meanwhile, the incidence and prevalence of CD in Western Countries have increased so greatly that awareness of CD has increased not only among clinicians, but also among the public and alternative medicine practitioners, often producing a great deal of confusion in the correct criteria for diagnosis [2,3].In this issue of Internal and Emergency Medicine, Licata and colleagues [4] report on a very hot topic, coeliac patients with only minimal intestinal lesions, and how to diagnose them. Other clinicians have investigated this point [5,6]. Among the first, Rostami [5] cast doubts about the great sensitivity of endomysium and gliadin antibodies in the diagnosis of CD in the cases with only mild lesions found on histology. The accuracy of antibody tests for CD was reviewed by Hill and colleagues [7], who found 95% mean sensitivity and 99% mean specificity for IgA endomysial antibodies, and 87 and 95%, respectively, for IgA tissue transglutaminase antibodies. Obviously, all the serology known for CD was developed using villous atrophy as the gold standard reference, and this can be considered a limit. It became clear that there were some subjects with stigmata of CD, who present positive antibodies many years before developing the enteropathy [8], and these patients were called potentials. Moreover, there are reports of relatives of coeliac patients who have only an increased number of intraepithelial lymphocytes with negative antibodies, but who should also be considered potentials. [9].On the other hand, the same question regarding the sensitivity of coeliac antibodies in those CD cases without frank atrophy could be put the other way around: are minimal lesions seen on histology specific for CD? Such a question would make the discussion even more complex. We cannot forget that Marsh himself, while classifying coeliac enteropathy histological findings by degree of severity, argues that none of the findings are specific for CD [10]. Many authors describe many alternative causes of intraepithelial lymphocytosis to CD [11][12][13][14]. Therefore, it is reasonable to argue that intraepithelial lymphocytosis, like inflammation, is a common pathological finding.The absence of genetic predisposition can help to exclude CD in borderline case, and a so-called gene-dose effect of HLA-DQ2 in the severity of intestinal atrophy and in the prognosis of refractory CD has been described. Nevertheless, researchers estimate that the genetic effect attributable to HLA is 53%, agreeing that other non-HLA regions must be involved. Moreover, DQ2...

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Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease.

Cited by 170 publications

References 23 publications

Celiac disease: diagnostic criteria in progress

Celiac disease: diagnostic criteria in progress

Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Histologic evidence for mild lesions in coeliac disease: the challenge is open

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