AARON LERNER
Carmel medical Center, Pediatric gastroenterology and nutrition unit, B. Rappaport School of Medicine, Technion-Israel Institute of Technology 7, Michal St. Haifa, 34362, Israel

Abstract

Celiac disease is an autoimmune condition affecting genetically susceptible individuals, following ingestion of wheat gluten, barley or-rye products. The only life long treatment is strict gluten free diet which is difficult personally and socially, affecting quality of life. Therefore, there is a need for alternative therapeutic modalities. New attractive potential therapies were starting to immerge: selecting, changing, degrading, manipulating or binding the dietary toxic environmental factors, decreasing intestinal permeability toward gluten or blocking the deamination of gluten by inhibiting tissue transglutaminase or the HLA-DQ presenting groove by carefully designed false peptide, shifting the typical Th1 to Th2 inflammatory reaction or antagonizing major proinflammatory cytokines, enhancing regulatory immune function or developing preventive vaccines, blocking adhesion molecule, inducing gluten oral or intranasal tolerance or applying epithelial repairing mitogens to oppose the mucosal destruction. The present alternative therapeutic strategies for celiac disease are reviewed.

INTRODUCTION

Celiac disease
Celiac disease (CD) is a life-long autoimmune condition (1) of the gastrointestinal tract, affecting the small intestine and extra-intestinal sites of genetically susceptible individuals. The worldwide mean incidence is 1:100. Gluten is the storage protein of wheat and its alcohol soluble gliadins are the offending toxic molecules of the disease together with structurally related components found in barley and rye. Tissue transglutaminase (tTG) is the auto antigen (2) and three main auto antibodies: anti endomysium, anti tTG and anti deaminated gliadin peptide are the most useful serological markers to screen for the disease (3). The genetic repertoire is expending, containing more then 50 non-HLA genes but HLA-DQ2 and HLA-DQ8 molecules are the most important, predisposing genetic factors.

Pathophysiology
The pathogenesis of the disease is being unraveled. Following is a stepwise description of the sequential chain of events operating in CD. After ingestion of gluten it is degraded to multiple segments. A 33 amino acid peptide, corresponding to amino acid 57-89 that is ...