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 have sp100 Abs. The sera of these patients exhibit a characteristic "nuclear dots" pattern in indirect immunofluorescence (IIF) on Hep-2 cells.
(Bolded areas represent the core epitope.) [2]
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.
Antinuclear antibodies are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some individuals, antibodies to human antigens are produced.
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. For example, the epitope is the specific piece of the antigen to which an antibody binds. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.
Autoimmune hepatitis, formerly called lupoid hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liver to be inflamed. Common initial symptoms include fatigue or muscle aches or signs of acute liver inflammation including fever, jaundice, and right upper quadrant abdominal pain. Individuals with autoimmune hepatitis often have no initial symptoms and the disease is detected by abnormal liver function tests.
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis.
Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts which normally allow bile to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease such as yellow discoloration of the skin and eyes, itching, and abdominal pain.
An autoantibody is an antibody produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases are caused by such autoantibodies.
Anti-mitochondrial antibodies (AMA) are autoantibodies, consisting of immunoglobulins formed against mitochondria, primarily the mitochondria in cells of the liver.
Dihydrolipoyl transacetylase is an enzyme component of the multienzyme pyruvate dehydrogenase complex. The pyruvate dehydrogenase complex is responsible for the pyruvate decarboxylation step that links glycolysis to the citric acid cycle. This involves the transformation of pyruvate from glycolysis into acetyl-CoA which is then used in the citric acid cycle to carry out cellular respiration.
Nuclear pore glycoprotein-210 (gp210) is an essential trafficking regulator in the eukaryotic nuclear pore complex. Gp-210 anchors the pore complex to the nuclear membrane. and protein tagging reveals its primarily located on the luminal side of double layer membrane at the pore. A single polypeptide motif of gp210 is responsible for sorting to nuclear membrane, and indicate the carboxyl tail of the protein is oriented toward the cytoplasmic side of the membrane.
Anti-glycoprotein-210 antibodies are directed at gp210 and are found within primary biliary cirrhosis (PBC) patients in high frequency. AGPA recognize the cytoplasmic-oriented carboxyl terminus (tail) of the protein. While AGPA is found as a prognostic marker in only a minority of PBC patients, those that did had higher mortality and were predicted a poor outcome. In addition, patients that responded to ursodeoxycholic acid (UDCA) therapy and, therefore, had AGPA reductions failed to develop end-stage liver disease relative to untreated cohort with anti-gp210 Ab. PBC patients with potentially destructive AGPA have increased expression of Nup210 in the bile duct, a potential immune tolerance-escaping factor.
Anti-p62 antibodies (AP62A) are found in a primary biliary cirrhosis. The p62 protein is also more frequent in Stage IV primary biliary cirrhosis and is prognostic for severe disease. The autoantigen is the nucleoporin 62kDA protein.
Sp100 nuclear antigen is an interferon stimulated antigen found in the cell nuclei of many human and higher animal cells. Autoantibodies directed against Sp100 are often found in patients with primary biliary cirrhosis. Histologically Sp100 'dots' regions of the cell nucleus. Viral infection and mitogens affect the expression of the Sp100 autoantigen. Cells grown in the presence of interferons revealed an increase both in size and number of the Sp100 protein-containing nuclear dots and increase the protein concentration. This raises "the question whether cytokine-mediated increase of Sp100 protein expression plays a role in induction of anti-Sp100 autoantibodies."
Nuclear bodies (also known as nuclear domains, or nuclear dots, are membraneless structures found in the cell nuclei of eukaryotic cells. Nuclear bodies include Cajal bodies, the nucleolus, and promyelocytic leukemia protein nuclear bodies. Nuclear bodies also include ND10s. ND stands for nuclear domain, and 10 refers to the number of dots seen.
HLA-DR53 is an HLA-DR serotype that recognizes gene products of HLA-DRB4 locus. There are 13 alleles at this locus that encode 7 proteins.
HLA-DR2 (DR2) of the HLA-DR serotype system, is a broad antigen serotype that is now preferentially covered by HLA-DR15 and HLA-DR16 serotype group. This serotype primarily recognizes gene products of the HLA-DRB1*15 and HLA-DRB1*16 allele groups.
HLA-DR4 (DR4) is an HLA-DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world.
Cancer/testis antigen 1 also known as LAGE2 or LAGE2B is a protein that in humans is encoded by the CTAG1B gene. It is most often referenced by its alias NY-ESO-1.
HLA A1-B8 is a multigene haplotype that covers the MHC Class I region of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles; common multigene haplotypes are generally the result of identity by descent from a common ancestor. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.
Anti-SSA autoantibodies are a type of anti-nuclear autoantibodies that are associated with many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus (SCLE), neonatal lupus and primary biliary cirrhosis. They are often present in Sjögren's syndrome (SS). Additionally, Anti-Ro/SSA can be found in other autoimmune diseases such as systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), rheumatoid arthritis (RA), and mixed connective tissue disease (MCTD), and are also associated with heart arrhythmia.