scholarly journals Missing Insight Into T and B Cell Responses in Dermatitis Herpetiformis

2021 ◽  
Vol 12 ◽  
Author(s):  
Esko Kemppainen ◽  
Teea Salmi ◽  
Katri Lindfors

Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion of gluten-containing cereals and characterized by granular deposits of immunoglobulin A in the papillary dermis. These antibodies target transglutaminase (TG) 3 and in the majority of patients they are also found in circulation. The circulating antibodies disappear and skin symptoms resolve as a result of gluten-free diet but the cutaneous anti-TG3 IgA deposits may persist for several years. In dermatitis herpetiformis, plasma cells secreting antibodies against TG3 are located in the intestinal mucosa similarly to those producing TG2 antibodies characteristic for celiac disease. In fact, both TG2- and TG3-specific plasma cells and gluten responsive T cells are found in dermatitis herpetiformis patients but the interplay between these cell populations is unknown. The small bowel mucosal damage in celiac disease is believed to be mediated by co-operation of cytotoxic intraepithelial T cells and the inflammatory milieu contributed by gluten-reactive CD4+ T cells, whereas the skin lesions in dermatitis herpetiformis appear to be devoid of gluten reactive T cells. Thus, how celiac disease-type intestinal T and B cell responses develop into an autoimmune condition affecting the skin is still incompletely understood. Finally, the skin and small bowel lesions may reappear upon reintroduction of gluten in patients treated with gluten-free diet but virtually nothing is known about the long-lived B cell and memory T cell populations activating in response to dietary gluten in dermatitis herpetiformis.

2015 ◽  
Vol 33 (2) ◽  
pp. 244-251 ◽  
Author(s):  
Emanuele Rondonotti ◽  
Silvia Paggi

Background: Because of its technical characteristics (i.e. 8-fold magnification, capability to inspect the entire small bowel) and minimal invasiveness, videocapsule endoscopy (VCE) has been proposed as a useful tool for managing patients with celiac disease (CD). Key Messages: Although VCE has been found to be highly sensitive and specific in identifying CD endoscopic markers, it is still inadequate to replace esophagogastroduodenoscopy (EGD) with biopsies in the diagnosis of CD. Nevertheless, it represents a reliable alternative in patients unable or unwilling to undergo EGD. Up to now, available studies have failed to identify any correlation between the length of small bowel involvement and the severity of symptoms. The available evidence on the use of VCE in diagnosing CD in equivocal cases (patients with positive serology and negative or nonspecific histology or those with negative serology and histologically proven villous atrophy) is limited, and its role is still under discussion. In CD patients not improving on gluten-free diet, a complete workup is necessary. In patients with nonresponsive (NRCD) or refractory CD (RCD), VCE has been shown to be able not only to detect significant findings, driving further management, but also to rule out major complications. Nevertheless, in this setting, the inability of VCE to take tissue samples and the risk of capsule retention can represent major limitations. Conclusions: At the present time, for diagnostic purposes, VCE can be proposed only in patients unable or unwilling to undergo EGD, whereas it could be useful in some equivocal cases. Conversely, there is no room for VCE either to estimate the length of the small bowel affected by villous atrophy or to follow up patients improving on gluten-free diet. In patients with NRCD or RCD, VCE can play a role, but it should be combined with other diagnostic techniques.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1665-1665
Author(s):  
R.K. Marwaha ◽  
Deepak Bansal ◽  
Amita Trehan ◽  
Akash Patel

Abstract Celiac disease (CD) is a malabsorptive disorder wherein the proximal small bowel mucosa is damaged as a result of dietary exposure to gluten. Children with intractable diarrhea and failure to thrive are diagnosed with relative ease. Diagnosis can however be challenging and is often delayed when children present with ‘difficult to treat anemia’, without overt gastrointestinal manifestations. The case records of 77 patients with CD were scrutinized retrospectively. Diagnosis was established with serology (tissue transglutaminase-IgA assay) in 46 (59.7%), serology along with small bowel mucosal biopsy in 23 (29.9%) and with biopsy alone in the remaining 8 (10.4%). All children belonged to the predominantly wheat consuming northern Indian states. The mean age at presentation was 99.1±34.8 months (median: 102, range: 22–168). Males outnumbered females in a ratio of 1.96:1. The mean duration of symptoms was 41±31.2 months (median: 36, range: 1–132). The overwhelming majority, i.e., 75 (97.4%) children had anemia (Hemoglobin <11 g/dL). Mean hemoglobin (Hb) was 7.0±2.2 g/dL (median: 7.2, range: 2.3–12.5). 52 (67.5%) had received iron supplements for sufficient lengths, without benefit. The red cell morphology was microcytic hypochromic in 37 (48%) and dimorphic in 33 (42.9%). A history of diarrhea was not forthcoming in 32 (41.6%) cases. 59 (76.6%) were malnourished, with a weight less than 80 % of expected for the age and 30 (39 %) were stunted, with a height falling below the 90% of expected. Two children had skin bleeds secondary to coagulopathy, due to Vitamin K malabsorption. In another 2, recurrent anemia was attributed to pulmonary hemosiderosis; further investigations for secondary causes unearthed CD. All children were initiated on an austere gluten free diet, along with iron and folic acid supplements for the initial 6–9 months. Mean duration of follow was 17.7±20.9 months. Improvement was perceptible within days of initiating gluten free diet. Of the 38 (49.4%) children who had a follow up of a year or longer, the mean Hb at the last visit had risen to 12.9±1.2 g/dL. Conclusions: Hematologists need to be aware of the mono-symptomatic presentation of CD with anemia. The typical period of presentation of CD is described to be between 6 mo and 2 yr of age. Prolonged duration of symptoms and a diagnosis at a relatively older age is striking in the index study. In a suggestive clinical background, identification of CD with serodiagnosis alone, without resorting to small bowel biopsy is increasingly gaining acceptance, as the specificity of newer serological assays is 95–98%. This is particularly true in tropical countries, where some degree of flattening of villi may be attributed to malnutrition and or infections, such as rotavirus enteritis, Giardia lamblia, or tropical sprue. A biopsy may be misleading in such cases. Heightened awareness is essential to identify CD at an early age, especially, in children in whom anemia is the dominant manifestation. The benefits of gluten free diet are apparent with the rise in hemoglobin and the improvement in growth parameters are gratifying both for physicians and the caretakers.


2014 ◽  
Vol 306 (6) ◽  
pp. G526-G534 ◽  
Author(s):  
Tobias L. Freitag ◽  
Jussi Loponen ◽  
Marcel Messing ◽  
Victor Zevallos ◽  
Leif C. Andersson ◽  
...  

The current treatment for celiac disease is strict gluten-free diet. Technical processing may render gluten-containing foods safe for consumption by celiac patients, but so far in vivo safety testing can only be performed on patients. We modified a celiac disease mouse model to test antigenicity and inflammatory effects of germinated rye sourdough, a food product characterized by extensive prolamin hydrolysis. Lymphopenic Rag1−/− or nude mice were injected with splenic CD4+CD62L−CD44high-memory T cells from gliadin- or secalin-immunized wild-type donor mice. We found that: 1) Rag1−/− recipients challenged with wheat or rye gluten lost more body weight and developed more severe histological duodenitis than mice on gluten-free diet. This correlated with increased secretion of IFNγ, IL-2, and IL-17 by secalin-restimulated splenocytes. 2) In vitro gluten testing using competitive R5 ELISA demonstrated extensive degradation of the gluten R5 epitope in germinated rye sourdough. 3) However, in nude recipients challenged with germinated rye sourdough (vs. native rye sourdough), serum anti-secalin IgG/CD4+ T helper 1-associated IgG2c titers were only reduced, but not eliminated. In addition, there were no reductions in body weight loss, histological duodenitis, or T cell cytokine secretion in Rag1−/− recipients challenged accordingly. In conclusion: 1) prolamin-primed CD4+CD62L−CD44high-memory T cells induce gluten-sensitive enteropathy in Rag1−/− mice. 2) Hydrolysis of secalins in germinated rye sourdough remains incomplete. Secalin peptides retain B and T cell stimulatory capacity and remain harmful to the intestinal mucosa in this celiac disease model. 3) Current antibody-based prolamin detection methods may fail to detect antigenic gluten fragments in processed cereal food products.


2015 ◽  
Vol 50 (4) ◽  
pp. 387-392 ◽  
Author(s):  
Teea T. Salmi ◽  
Kaisa Hervonen ◽  
Kalle Kurppa ◽  
Pekka Collin ◽  
Katri Kaukinen ◽  
...  

2019 ◽  
Vol 139 (10) ◽  
pp. 2108-2114 ◽  
Author(s):  
Eriika Mansikka ◽  
Kaisa Hervonen ◽  
Katri Kaukinen ◽  
Tuire Ilus ◽  
Pia Oksanen ◽  
...  

2017 ◽  
Vol 49 (4) ◽  
pp. 412-416 ◽  
Author(s):  
Konstantinos Efthymakis ◽  
Angelo Milano ◽  
Francesco Laterza ◽  
Mariaelena Serio ◽  
Matteo Neri

Gut ◽  
1998 ◽  
Vol 43 (4) ◽  
pp. 490-493 ◽  
Author(s):  
T Reunala ◽  
P Collin ◽  
K Holm ◽  
P Pikkarainen ◽  
A Miettinen ◽  
...  

Objectives—Recent studies on coeliac disease have shown that oats can be included in a gluten-free diet without adverse effects on the small bowel. The presence of a rash is also a sensitive indicator of gluten ingestion in dermatitis herpetiformis, and this was used to study whether patients with this disease could also tolerate oats.Patients/Methods—Eleven patients with dermatitis herpetiformis in remission on a gluten-free diet were challenged daily with 50 g oats for six months. Clinical symptoms were recorded, serum samples taken, and skin and small bowel biopsies performed before and after the oat challenge. A control group comprised of 11 patients with dermatitis herpetiformis on a conventional gluten-free diet was also studied.Results—Eight patients challenged with oats remained asymptomatic, two developed a transient rash, and one withdrew because of the appearance of a more persistent but mild rash. Three of the 11 controls also developed a transient rash. IgA endomysial antibodies remained negative in all patients. The small bowel villous architecture, the densities of intraepithelial CD3 and α/β and γ/δ T cell receptor positive lymphocytes and crypt epithelial cell DR expression remained unaltered during the oat challenge.Conclusions—The results confirm the absence of oat toxicity on the gluten sensitive small bowel mucosa and suggest that the rash in patients with dermatitis herpetiformis is not activated by eating oats.


2007 ◽  
Vol 22 (8) ◽  
pp. 1300-1305 ◽  
Author(s):  
Surender K Yachha ◽  
Anshu Srivastava ◽  
Samir Mohindra ◽  
Narendra Krishnani ◽  
Rakesh Aggarwal ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3993
Author(s):  
Bara Aljada ◽  
Ahmed Zohni ◽  
Wael El-Matary

The gluten-free diet (GFD) has gained popularity beyond its main medical indication as the treatment for gluten-induced immune-mediated disorders such as celiac disease (CD), dermatitis herpetiformis, gluten ataxia, wheat allergy, and non-celiac gluten sensitivity. However, the diet carries some disadvantages such as elevated costs, nutritional deficiencies, and social and psychological barriers. The present work aims to review indications, proven benefits, and adverse events of a gluten-free diet. Close follow-up with patients following the diet is recommended. More data is needed to assess the effectiveness of the diet in managing mental and cognitive disorders and to establish a connection between the brain and gluten.


Sign in / Sign up

Export Citation Format

Share Document