Anti-glycoprotein-210 antibodies explained

Anti-glycoprotein-210 antibodies (AGPA, anti-gp210, anti-nup210, anti-np210) are directed at gp210^[1] and are found within primary biliary cirrhosis (PBC) patients in high frequency. AGPA recognize the cytoplasmic-oriented carboxyl terminus (tail) of the protein.^[2] 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.^[3] 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.^[4] PBC patients with potentially destructive AGPA have increased expression of Nup210 in the bile duct, a potential immune tolerance-escaping factor.^[5]

Anti-mitochondrial, anti-centromere^[6] and anti-p62 antibodies are also found in (PBC). While patients with AGPA progress toward end-stage liver failure, patients with anti-centromere antibodies often progress toward portal hypertension, further indicating a specific role of the AGPA in PBC.

Notes

The glycoprotein gp210 is commonly used in the literature. The gene, NUP210, encodes the nuclear pore (nuclear porin) glycoprotein-210 that is a major component of the human nuclear pore complex.

Notes and References

1. Courvalin JC, Lassoued K, Worman HJ, Blobel G . Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis . J. Exp. Med. . 172 . 3 . 961–7 . 1990 . 2167346 . 10.1084/jem.172.3.961 . 2188537 .
2. Nickowitz RE, Worman HJ . Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein Gp210 . J. Exp. Med. . 178 . 6 . 2237–42 . 1993 . 7504063 . 10.1084/jem.178.6.2237 . 2191303 .
3. Itoh S, Ichida T, Yoshida T . Autoantibodies against a 210 kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis . J. Gastroenterol. Hepatol. . 13 . 3 . 257–65 . 1998 . 9570238 . 10.1111/j.1440-1746.1998.01553.x . etal.
4. Nakamura M, Shimizu-Yoshida Y, Takii Y . Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis . J. Hepatol. . 42 . 3 . 386–92 . 2005 . 15710222 . 10.1016/j.jhep.2004.11.016. etal.
5. Nakamura M, Takii Y, Ito M . Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis . J. Autoimmun. . 26 . 2 . 138–45 . 2006 . 16337775 . 10.1016/j.jaut.2005.10.007. etal.
6. Nakamura M, Kondo H, Mori T . Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis . Hepatology . 45 . 1 . 118–27 . 2007 . 17187436 . 10.1002/hep.21472. etal. free .