Molecular dissection of the tissue transglutaminase autoantibody response in celiac disease.
Celiac disease (CD) is an intestinal malabsorption characterized by intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and tissue transglutaminase, an autoantigen located in the endomysium. Tissue transglutaminase belongs to the family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. The role of gliadins in eliciting the immune response in CD and how transglutaminase is linked to the primary reaction are still unclear. In this work, we report the production and analysis of six phage Ab libraries from the peripheral and intestinal lymphocytes of three CD patients. We were able to isolate Abs to transglutaminase from all intestinal lymphocytes libraries but not from those obtained from peripheral lymphocytes. This is in contrast to Abs against gliadin, which could be obtained from all libraries, indicating that the humoral response against transglutaminase occurs at the local level, whereas that against gliadin occurs both peripherally and centrally. Abs from all three patients recognized the same transglutaminase epitopes with a bias toward the use of the V(H)5 Ab variable region family. The possible role of these anti-transglutaminase Abs in the onset of CD and associated autoimmune pathologies is discussed.
Dipartimento di Biologia, Università di Trieste, Trieste, Italy. marzari@icyeb.trieste.it
R
R
Marzari
D
D
Sblattero
F
F
Florian
E
E
Tongiorgi
T
T
Not
A
A
Tommasini
A
A
Ventura
A
A
Bradbury
D000328:Adult; D000595:Amino Acid Sequence; D000915:Antibody Affinity; D001323:Autoantibodies / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D002446:Celiac Disease / Q000201:enzymology* / Q000276:immunology*; D002999:Clone Cells; D018604:Epitope Mapping; D005312:Fetal Blood / Q000276:immunology; D019085:Fluorescent Antibody Technique, Direct; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D015723:Gene Library; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017912:Inovirus / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000276:immunology; D009154:Mutation; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012995:Solubility; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D001324:Autoantigens; D007106:Immune Sera; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins