• Logo
  • SBMUJournals

Primary biliary cholangitis with contemporary presence of anti-mithocondrial and anti-rods and rings autoantibodies: literature first case

Roberto Assandri
54

Views

PDF

Abstract

Primary biliary cholangitis , previously known as primary biliary cirrhosis (PBC), is the most common autoimmune diseases of the liver (ALD). Patients with PBC may present with typical biliary pattern symptoms. Also the presence of anti mitochondrial autoantibodies (AMAs) is the laboratory hallmark of PBC, which molecular target antigens are members of 2-oxoacid dehydrogenase complex of enzymes.

In recent years, autoantibodies (Aab) targeting subcellular structures described as the rods and rings (R&R) pattern in HEp-2 ANA have been presented as a unique and particular case of Aab generation. These R&R structures are composed of inosine monophosphate dehydrogenase type 2 (IMPDH2), and their formation can be induced in vitro by several small-molecule inhibitors.

Aab targeting these relatively unknown structures have been almost exclusively observed in hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferon-a/ribavirin (IFN/RBV) therapy. Literature showed that anti-RR Aab have not been found in treatment-naïve HCV patients or in patients from any other disease.

Now We present and characterized a case patient with contemporary presence of AMAs and R&R Aab in PBC, without any laboratory evidences of HCV and/or other hepatic virus infection.

For our knowledge this is the first case described in the Literature.

R&R Aab in patients without any clinical/laboratory signs or symptoms of Hepatitis virus and without pharmacological therapy open the window to the alternative scenario: the association of these Aab to ALD. The AMA-negative cases are an intriguing diagnostic problem. Our work demonstrated that R&R Aab can be present in PBC case.  The interesting idea suggesting suggested that R&R Aab may be present also in AMA-negative PBC and they can considered a new diagnostic tool in this specific clinical condition.

Other study and cases are needed but the presence of R&R Aab linked with AMAs and PBC may be explained by alterations in immune regulation caused by autoimmunity in a particular genetic background.


Keywords

Primary biliary cholangitis , rods and rings Autoantibodies, Anti-Mithocondrial antibodies, Autoimmune liver diseas

References

References

Koulentaki M, Mantaka A, Sifaki-Pistolla D, Thalassinos E, Tzanakis N, Kouroumalis E. Geoepidemiology and space-time analysis of primary biliary cirrhosis in Crete, Greece. Liver Int. 2014;34(7):e200–e207.

Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. Hepatology. 2009;50(1): 291–308

Yamagiwa S, Kamimura H, Takamura M, Aoyagi Y. Autoantibodies in primary biliary cirrhosis: recent progress in research on

the pathogenetic and clinical significance. World J Gastroenterol. 2014;20(10):2606–2612.

Benson GD, Kikuchi K, Miyakawa H, Tanaka A, Watnik MR, Gershwin ME. Serial analysis of antimitochondrial antibody in patients with primary biliary cirrhosis. Clin Dev Immunol. 2004;11(2):129–133.

Calise, S. J., Carcamo,W. C., Ceribelli, A., Dominguez, Y., Satoh, M. Chan, E. K. (2014a). Antibodies to rods and rings. In Autoantibodies (ed. Y. Shoenfeld, P. L. Meroni and M. E. Gershwin), pp. 161-168. Elsevier Science.

Carcamo, W. C., Ceribelli, A., Calise, S. J., Krueger, C., Liu, C., Daves, M., Villalta, D., Bizzaro, N., Satoh, M. and Chan, E. K. L. (2013). Differential reactivity to IMPDH2 by anti-rods/rings autoantibodies and unresponsiveness to pegylated interferon-alpha/ribavirin therapy in US and Italian HCV patients. J. Clin. Immunol. 33, 420-426

Keppeke, G. D., Satoh, M., Ferraz, M. L., Chan, E. K. and Andrade, L. E. (2014). Temporal evolution of human autoantibody response to cytoplasmic rods and rings structure during anti-HCV therapy with ribavirin and interferon-alpha. Immunol. Res. 60, 38-49.

Joan Climent, Francisco Morandeira, José Castellote, Javier Xiol, Jordi Niubó, Laura Calatayud, Mariona Mestre & Jordi Bas (2015): Clinical correlates of the “rods and rings” antinuclear antibody pattern, Autoimmunity, DOI: 10.3109/08916934.2015.1118762

McNally RJ, James PW, Ducker S, Norman PD, James OF. No rise in incidence but geographical heterogeneity in the occurrence of primary biliary cirrhosis in North East England. Am J Epidemiol 2014; 179: 492–98

Invernizzi P, Battezzati PM, Crosignani A, et al. Peculiar HLA polymorphisms in Italian patients with primary biliary cirrhosis. J Hepatol 2003; 38: 401–06

Carey EJ, Ali AH, Lindor KD. Primary biliary cirrhosis. Lancet. 2015;386(10003):1565–1575

Han E, Joa SJ, Lee H, et al. Clinical relevance of combined antimitochondrial M2 detection assays for primary biliary cirrhosis. Clin Chim Acta. 2017;464:113–117

Carcamo, W. C., Calise, S. J., von Mü hlen, C. A., Satoh, M. and Chan, E. K. L. (2014). Molecular cell biology and immunobiology of mammalian rod/ring structures. Int. Rev. Cell Mol. Biol. 308, 35-74.

Probst, C., C. Radzimski, I. M. Blo¨cker, et al. 2013. Development of a recombinant cell-based indirect immunofluorescence assay (RC-IFA) for the determination of autoantibodies against ‘‘rings and rods’’-associated inosine 5’-monophosphate dehydrogenase 2 in viral hepatitis C. Clin. Chim. Acta418: 91–96.

Keppeke, G. D., E. Nunes, M. L. G. Gomes Ferraz, et al. 2012. Longitudinal study of a human drug-induced model of autoantibody to cytoplasmic rods/rings following HCV therapy with ribavirin and interferon-a. PLoS One 7: e45392. 5.

Shaikh, Y., A. Krantz, and Y. El-Farra. 2013. Anti-rods and rings autoantibodies can occur in the hepatitis c-naı¨ve population. J. Prev. Hyg. 54: 175–180.

Allisona, A. C., and E. M. Euguia. 2000. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47: 85–118.

Seeling, H. P., H. Appelhans, O. Bauer, et al. 2011. Autoantibodies against inosine-50 monophosphate dehydrogenase 2—characteristics and prevalence in patients with HCV-infection. Clin. Lab. 57: 753–765.

Chan, E. S., and B.N. Cronstein. 2002. Molecular action bof methotrexate in inflammatory diseases. Arthritis Res. 4: 266–273

Climent, J. , Morandeira, F, Castellote, J ., Xiol,J., Niubó,J., Calatayud, L.,Mariona (2015): Clinical correlates of the “rods and rings” antinuclear antibody pattern, Autoimmunity

Granito A, Muratori P, Quarneti C, Pappas G, Cicola R, Muratori L. Antinuclear antibodies as ancillary markers in primary biliary cirrhosis. Expert Rev Mol Diagn. 2012;12(1):65–74

Assandri R, Monari M, Montanelli A. Development of systemic sclerosis in patients with autoimmune hepatitis: an emerging overlap syndrome. Gastroenterol Hepatol Bed Bench 2016;9:211-9.

Valaperta S, Alpini C, Bottone MG, Monari M, Assandri R, Montanelli A. Autoanticorpi anti-Golgi: anche l’occhio vuole la sua parte. Recenti Prog Med 2011;102:11-3

Assandri R, Serana F, Montanelli A. Development of PBC/SSc overlap syndrome in chronic GVHD patient: Immunological implications in the presence of mitochondrial, nucleolar and spindle midzone autoantigens. Gastroenterol Hepatol Bed Bench 2017;10(4):323-331




DOI: https://doi.org/10.22037/ghfbb.v0i0.1433