Celiac Disease

Celiac Disease is an autoimmune disorder that is becoming more recognized among the medical profession and is a disease that is being diagnosed on a more frequent basis based on the growing knowledge of the disease. Celiac disease is linked to interactions between gluten and immune, genetic, and environmental factors (1). One known cause of celiac disease is the ingestion of gluten in genetically predisposed people (1). Gluten is the protein storage for wheat, barley, and rye, a major food component ingested by most individuals. Celiac disease was once known as celiac sprue, a rare malabsorption syndrome of childhood and is now known as a common condition affecting many organ systems (1).

According to Green et. al., gluten is digested by luminal enzymes into amino acids and peptides. The main peptide used in the innate immune system is the gliadin peptides which cause a change in the epithelium. Gliadin peptides cause damage to the epithelial cells causing an over expression of Interleukin-15. When Interleukin 15 is expressed, intraepithelial lymphocytes are activated which causes the activated cells to become cytotoxic and kill the enterocytes marked with MIC-A (major-histocompatibility-complex class I chain-related A) (1). In the adaptive immune system gliadin causes changes in the lamina propria. Gliadin enters the lamina propria during infection, where gliadin is deamidated by tissue transglutaminase. The adaptive immune response is mediated by the glidian-reactive CD4+ T cells which are bound to HLA class II molecules on APCs (1). Interferon-γ cytokines are released by the T cells causing an inflammatory response.

CD8+ T lymphocytes represent one of the diagnostic hallmarks of Celiac disease (3). These CD8+ T lymphocytes recognize peptides in HLA Class I molecules which are found in patients with celiac disease. According to Gianfrani et. al., the peptide A-gliadin is selectively recognized by CD8+ T lymphocytes from HLA-DQ2 or HLA-DQ8 celiac patients. Studies have shown that gliadin-specific CD8+ T cells infiltrating celiac mucosa, along with CD4+ T cells may play an important role in CD pathogensis (3).

Genetic factors of the disease seem to be strongly linked in determining individuals who have a high risk of developing the disease. Because the disease is linked to the adaptive immune response, specific class II HLA genes play a specific role on the development of celiac disease. Persons with alleles that encode for HLA-DQ2 or HLA-DQ8 have a high risk of developing (2). Green et al. say that the presence of these HLA genes is necessary but not sufficient in the development of Celiac disease because there are many people who do not have Celiac Disease but carry these alleles. It is known that HLA-DQ2 is found in 90-95% of patients with celiac disease, while the HLA-DQ8 is identified in the rest of the patients (1). The presence of absence in these HLA genes is important in determining who should be tested for the disease if symptoms appear.

Diagnosing celiac disease has become increasingly easier with HLA assessment, biopsy, and serological testing. Antibody testing is used to diagnose celiac disease. The main antibodies used are the antigliadin antibodies, connective tissue antibodies, and antibodies that are directed against tissue transglutaminase (2). Patients who have celiac disease often have low IgA endomysial antibodies and IgA antitissue antibodies against tissue transglutaminase. If levels from serological testing indicate a possibility of disease, then a biopsy of the small intestine is performed.

It is interesting to note that both the innate and adaptive immune response is involved in Celiac disease. Many studies have shown that the activation of the innate immune response sets the stage for activation of the adaptive immune response, by the activating of dendritic cells (3). There are still many unanswered questions as to the true mechanisms behind this disease, but with the knowledge of the immune response pathways, there is a better understanding of the processes and roles that are actually occurring in Celiac’s Disease.

(1) Peter H.R. Green, M.D., and Christophe Cellier, M.D., Ph.D. Celiac Disease. N Engl. J Med. 2007 Oct 25;357(17):1731-43.

(2) Armin Alaedini, Haruka Okamoto, Chiara Briani, Kurt Wollenberg, Holly A. Shill, Khalafalla O. Bushara, Howard W. Sander, Peter H. R. Green, Mark Hallett, and Norman Latov. Immune Cross-Reactivity in Celiac Disease: Anti-Gliadin Antibodies Bind to Neuronal Synapsin I. Journal of Immunology. May 2007; 178: 6590 - 6595.

(3) Gianfrani C, Auricchio S, Troncone R. Adaptive and innate immune responses in celiac disease. Immunol Lett. 2005 Jul 15;99(2):141-5.