Bibliographic updates

The Monthly choice - October 2015
Claude MOLINA* & Jacques GAYRAUD**

1.    Gluten-related disorders
2.    Celiac disease in collision with Asthma: role of Leukotrienes
3.    Food   Allergy  and  Celiac Disease                  
4.    Allergic multi-organ diseases induced by Wheat–Flour                                
5.    Emerging therapeutic options for the treatment of Asthma

1.    Gluten-related disorders:
M.F.Martinez-Munoz et al : Ped.All.Immunol  2015 Sept. on line*
Theme: Food allergy – Wheat.
Key words: Gluten – IgE – Celiac disease – Gluten sensitivity

Gluten, the main structural protein complex of wheat, is responsible for 3 different immune responses with various clinical, pathogenic and epidemiologic expression:
1) IgE-mediated Wheat allergy with typical manifestations of Th2 response: dermatologic, respiratory, intestinal anaphylactic  reactions.  
2) Celiac disease CD, auto-immune, gliadin-specific Th1 cell response, with intestinal (diarrhea) or extra-intestinal (weight loss, anemia) symptomatic or latent form discovered by serological or genetic screening.  
3) Gluten sensitivity, possibly immune-mediated, with intestinal symptoms after absorption of gluten or cereals, in non allergic, non-celiac patients and source of popularity and  often excessive gluten-free diet.                                   
(A recent state of art review on CD is published in BMJ  5 october 2015 351;h4347 B.Lebwohl et al )

2.    Celiac disease in collision with Asthma: role of Leukotrienes
F.Tang et al Journal of Exp.Medicine 2015  212 10 1487-1495 and J. Groojans et al  idem 1485.
Theme: Food allergy – Wheat.
Key words: Celiac disease – Asthma – Leukotrienes.

Inflammatory T cell response to dietary gluten in genetically susceptible host, Celiac disease is characterized by injury to intestinal epithelial cells, atrophy of the villi, caused by infiltrating cytotoxic C D8 cells. Antigen Gluten, elimination of which is a recognized therapy, promotes IL15 which in turn recruits additional toxic cells responsible for up-regulation of cysteinyl-leukotrienes (CystLts), demonstrable in active celiac but not in healthy or on gluten-free patients. These CystLts are metabolites of Arachidonic acid, linked to allergic disorders including Asthma. Moreover, Montelukast, inhibitor of CystLts is beneficial in Asthmatics and pre-treatment of  intestinal toxic cells decrease their cytolytic capacity. So, this drug may be a potent therapeutic target for celiac disease.

3.    Food Allergy and Celiac Disease (CD)            
R.Pillon et al Allergy 2015 701346-1349  **                              
Theme: Food allergy – Wheat.
Key words: Celiac disease - IgE

The Spanish authors*  report the first case of wheat allergy associated with latent celiac disease in a 19 months – old boy, suffering atopic dermatitis and bronchospasm; the diagnosis of CD was made by family history and genetic results (HLA –DQA1 05 cis DQB 02); wheat allergy occurred  at 5 years and grass pollen allergy at 11.                     
In the second patient, a girl (17 months), CD diagnosed  by serum IgA anti-transglutaminase and anti-endomysium and intestinal biopsy. Grass pollen allergy occurred at 6 years and wheat allergy (IgE +) at 12, revealed by inadvertent ingestion of wheat.
Italian pediatricians **screening for CD 319 patients with severe food allergy observed a prevalence of 5% (1% among healthy school children) and recommend routine genetic and serological markers in case of severe reactions against food proteins with elevated IgE levels.  

4.    Allergic multi-organ diseases induced by Wheat–Flour
E.Gomez-Torrijos et al :JACI 2015 October  1114-1116        
I.Sanders et al : JACI 2015135 1529-1537
Theme: Food allergy – Wheat.
Key words: Rhinitis – Asthma – Anaphylaxis - Eosinophilic Esophagitis – Albumin – Globulins – Gliadins – Glutenins.

Clinical profiles of WF allergy and component resolved diagnosis revealed high degree of heterogeneity in the recognized allergens (more than 19 recombinant proteins and 2 carbohydrate determinants). It appears that mainly salt-soluble proteins fractions (albumin, globulins) are associated with baker’s Asthma and Rhino-sinusitis, and prolamine (gliadins,glutenins) with wheat-dependant Anaphylaxis induced by exercise.  Both fractions, salt soluble and insoluble,   are incriminated in Food allergy. In fact Gliadins may be also causative in baker’s Asthma.                                                        
And now, it has been recently reported the case of a 31 years old  young woman exposed since birth in the bakery of her family, where she  subsequently worked,  who successively suffered Rhino-sinusitis with Ocular symptoms  and Asthma  then Eosinophilic Esophagitis induced by inhalable wheat flour, without gastro-intestinal symptoms by ingestion of cereals products. It is the first case of Occupational Allergic Eosinophilic Esophagitis triggered by inhalation. All these disorders went into remission when the patient was removed from the workplace.

5.    Emerging therapeutic options for the treatment of Asthma
R.A.McIvor  Annals of Allergy, Asthma, Immunol.2015 115 4 265-271
Theme: Respiratory allergy – Asthma – Allergy treatment .
Key words: Monoclonal antibodies – Phosphodiesterase – Muscarinic antagonists

Despite treatment according to guidelines, approximately 40% of patients remain symptomatic. A search, restricted to the previous ten years was performed by this Canadian author about emerging therapies in phase 2 or 3 development. They include monoclonal antibodies (anti-interleukin 5 or anti-IL 13 agents) a chemoattractant molecule expressed on a Th2–lymphocyte antagonist (OC000459), a phosphodiesterase 4: Roflumilast and Long-Acting Muscarinic–Antagonists. The most advanced drug  is  inhaled Thiotropium. In 3 randomized trials, including more than 1000 patients, this LAMA appears to be well tolerated, and efficacious as an addition to maintenance treatment with ICS + LABA in adolescents or adults  with moderate to severe asthma, once daily at 0,2µg dose .            
(G.J.Rodrigo Annals of A.A.I  2015  115  3  211-216)         
Nevertheless, the authors remind us that it should be considered that clinical trial efficacy is often distinct from real-life effectiveness.

*All the references may be found in PubMed or sent on demand to:
Claude Molina                    
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Jacques Gayraud
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Last updated 17 November 2015