Nutrition Guide

A deficiency in any of the enzymes of this complex as well as an inhibition of the complex as a whole is responsible for maple syrup urine disease.

This enzyme is an autoantigen recognized in primary biliary cirrhosis, a form of acute liver failure. These antibodies appear to recognize oxidized protein that has resulted from inflammatory immune responses. Some of these inflammatory responses are explained by gluten sensitivity.[1]. Other mitochondrial autoantigens include pyruvate dehydrogenase and branched chain oxoglutarate dehydrogenase, which are antigens recognized by anti-mitochondrial antibodies.

This complex is also analogous to the alpha-ketoglutarate dehydrogenase complex in the citric acid cycle and the pyruvate dehydrogenase complex creating acetyl-CoA prior to the citric acid cycle.

This complex requires the following 5 cofactors:
Thiamine diphosphate
FAD
NAD+
Lipoate
Coenzyme A

The branched-chain ?-keto acid dehydrogenase complex is a combination of enzymes responsible for the degradation of the branched chain amino acids. Examples of these include valine, isoleucine, and leucine.

Anti-thrombin antibodies are autoantibodies directed against thrombin that may constitute a fraction of lupus anticoagulant and are seen an increased levels in systemic lupus erythematosus.

crystal structure of thrombin.

In mammals, there is normally occurring anti-thrombin activity (antithrombin III), which can be distinguished from autoimmune anti-thrombin. Anti-thrombin antibodies can react with both types of thrombin in the antithrombin-thrombin complex.[1] Antibodies (IgG) against thrombin can strongly inhibit its activity.[2] Inhibitory anti-thrombin antibodies can be divided into 2 groups, those that inhibit coagulation activity and those the inhibit coagulation and amidase activity.[3] Autoimmune anti-thrombin was also found to inhibit the binding of antithrombin III to thrombin.[4] Such activities are more often found with primary biliary cirrhosis.[4][5] Multiple studies have shown, however, that despite autoimmune anti-thrombin thrombin inhibitory activity, these antibodies correlate with thrombotic events, so that they may also perturb the regulation of coagalatory factors.

Other than antibodies to thrombin, antibodies to vascular heparin sulfate appear to interfere with antithrombin-thrombin interaction.[6]

antigenic region 1 - positions 296-311 - Sequence (I K K E K P F S N S K V E C Q A)
antigenic region 2 - positions 332-351 - Sequence (E G S T D V D E P L E V F I S A P R S E)

(Bolded areas represent the core epitope)[2]

Anti-sp100 antibodies are found in association with primary biliary cirrhosis.[1] The autoimmune target of anti-sp100 is the sp100 nuclear antigen which was identified by its association with primary biliary cirrhosis. 20-30% of patients suffering from primary biliary cirrhosis sp100 Abs.

Anti-Tissue Transglutaminase (tTG) Antibodies Also Found in Inflammatory Bowel Disease
Tg6 Antibody Plays a Key Role in Celiac-Related Neurological Disorders Celiac.com 09/02/2008

Genetics of coeliac disease is the common genetic factor for ATA. However studies of children with coeliac disease reveals that patients with DR7 have higher titers to ATA [21]. The DR7 is commonly found with HLA-DR5-DQ7/DR7-DQ2 phenotype in celiac disease. DR7-DQ2 homozygotes are also found.

The antibodies to tissue transglutaminase follow a complex pathway of generation. For most antigens, T-cells specific to those antigens develop, for autoimmunity autoreactive T-cells are not suppressed or antigens escape the protective process. T-cells are stimulated by antigen, presented by MHC molecules (HLA in humans) and surface IgM on antigen reactive B-cells. These T-helper cells then stimulate B-cells to multiply and mature into plasma cells that make IgG to that protein.

For tTG autoimmunity (CD), T-cells are generated against wheat gliadin and similar gluten proteins of the trib Triticeae. The T-cells are defined by the ability to react to HLA-DQ8 and DQ2.5 restricted antigens and gliadin is one of the antigens. Gliadin is a favored dietary substrate for transglutaminase because of many enzyme reaction sites on gliadin. In disease, transglutaminase reacts with gliadin forming a linkage[18]. In forming this bond transglutaminase becomes linked to T-cell epitopes on gliadin. B-cells with surface IgM that react to transglutaminase can present it with bound gliadin peptides to T-cells which stimulate B-cell maturation and proliferation to plasma cells making IgA or IgM.

ATA correlates with severity of CD. A recent study of children demonstrates that the level of ATA in correlates with the scalar Marsh score for the disease in the same patient.[19]

ATA changes the behavior of tTG. Some studies have revealed that antibodies increase the activity of tTG, instead of inhibiting activity as is commonly encountered with function alterning antibodies. A recent study has shown that ATA also modify and increase replication in intestinal epithileal cells, by apparently interacting with cell-surface transglutaminase.[20]