Anti-Tissue Transglutaminase Can Lead to Hashimoto’s Thyroiditis
Celiac, gluten intolerance, causes intestinal inflammation and immunological presentation of the common intestinal protein, tissue transglutaminase (tTG). The result is anti-tTG autoantibodies that stimulate an immune attack on intestines and other tissues.
Heparan-Binding Proteins Involved in Autoimmunity and Allergy
Those familiar with my blog know that I am obsessed with heparin-binding protein domains. The reason that I am focused on these parts of proteins, is because most cells rapidly sweep heparan sulfate polysaccharides across their surfaces from sites of secretion to sites of internalization. During inflammation, proteins with strong heparin-binding domains, consisting of triplets of basic amino acids, e.g. KRK (lysine-arginine-lysine), are internalized along with the heparan sulfate. The result is an aberrant presentation of these internalized proteins to the immune system and production of inappropriate antibodies, e.g. autoantibodies.
Basic Triplets in Hasimoto’s AutoantigensOne of my hobbies is checking for the unusual occurrence of basic triplets in autoantigens and allergens. I have found dozens of examples. The most recent is associated with Hashimoto’s Thyroiditis. I knew that attack on the thyroid was common in celiacs, because the celiac autoantigen tTG (it has a basic triplet) is also present in the thyroid and the celiac autoantibodies to tTG also cause an attack on the thyroid. But the autoantigen for Hashimoto’s Thyroiditis is thyroid peroxidase (TPO).
I was momentarily perplexed, but then examined the TPO amino acid sequence and immediately found a couple of basic triplets (
KKR and
KRK).
MRALAVLSVTLVMACTEAFFPFISRGKELLWGKPEESRV
SSVLEESKRLVDTAMYATMQRNL
KKRGILSPAQLLSFSK
LPEPTSGVIARAAEIMETSIQAM
KRKVNLKTQQSQHPTD
ALSEDLLSIIANMSGCLPYMLPPK...
Hashimoto’ Thyroiditis Linked to CeliacThen, I did a PubMed search for “celiac and Hashimoto’s”. As expected, there is a recent paper (see below) that shows that celiac commonly leads to Hashimoto’s Thyroiditis.
An obvious explanation is that the initial attack on the thyroid by anti-tTG autoantibodies of celiac leads to thyroid inflammation and presentation of TPO, with a second round of autoantibodies produced to TPO resulting in Hashimoto’s Thyroiditis. Celiac may be the initial autoimmune trigger for many other autoimmune diseases and allergies.
Autism has been associated with maternal autoimmunity and placental abnormalities. Guess where tTG is found in high abundance?
reference:
Bardella MT, Elli L, Matteis SD, Floriani I, Torri V, Piodi L. Autoimmune disorders in patients affected by celiac sprue and inflammatory bowel disease. Ann Med. 2009;41(2):139-43.