Sains Malaysiana 51(11)(2022): 3731-3739
http://doi.org/10.17576/jsm-2022-5111-17
Determination of Non-Organ Specific
Autoantibodies in Patients with Chronic Hepatitis C and
Association with HLA DRΒ1 (*04) Allele
(Penentuan Autoantibodi Khusus Bukan Organ pada Pesakit Hepatitis C Kronik dan Perkaitan dengan Alel HLA DRΒ1 (*04))
FATIMA AYUB1, ROMEEZA TAHIR1,*, MUHAMMAD KASHIF1,2, KHURSHEED
JAVAID1, FAHEEM SHAHZAD1, SHAH JAHAN1 &
NADEEM AFZAL1
1Department of Immunology, University of Health
Sciences, Khyaban-e-Jamia Punjab, 54000, Lahore, Pakistan
2Department of Oral Pathology, Bakhtawar Amin Medical & Dental College, Multan, Pakistan
Diserahkan: 24 Mei 2021/Diterima: 28 Jun 2022
Abstract
The regulation of immune
mechanisms is controlled by major histocompatibility complex/human leukocyte
antigen (MHC/HLA). Polymorphisms of the HLA region have an impact on
susceptibility to complex infectious and autoimmune diseases. The present study was carried out to determine the frequencies of
ASMA, AMA, ANA, dsDNA, and anti-LKM-1 auto-antibodies in hepatitis
C patients and to determine their association with the HLA DRβ1
(*04) locus. It was a cross-sectional,
analytical study, and 86 patients with chronic HCV were recruited. The
presence of auto-antibodies (ASMA, AMA, ANA, dsDNA, and anti-LKM-1) was determined by indirect immunofluorescence and ELISA,
while the HLA DRβ1 (*04) allele was assessed by
sequence-specific conventional PCR. ANA was detected in 41%, ASMA in 17.4%, AMA
in 7%, LKM-1 in 5.8% dsDNA in 4.6% of CHC patients while HLA-DRβ1
(*04) was present in 3.5% of patients, but this was not significantly
associated with these auto-antibodies.
Keywords:
Auto-antibodies; HCV; hepatitis C; HLA DRβ1; immunofluorescence
Abstrak
Pengawalaturan mekanisme imun dikawal oleh kompleks histoserasian utama/antigen leukosit manusia (MHC/HLA). Polimorfisme rantau HLA mempunyai kesan ke atas kerentanan kepada penyakit berjangkit dan autoimun yang kompleks. Kajian ini dijalankan untuk menentukan kekerapan ASMA, AMA, ANA, dsDNA dan anti-LKM-1 auto-antibodi pada pesakit hepatitis C dan untuk menentukan hubungan mereka dengan lokus HLA DRβ1 (*04). Ia adalah kajian keratan rentas, analisis dan 86 pesakit dengan HCV kronik telah diambil. Kehadiran auto-antibodi (ASMA,
AMA, ANA, dsDNA dan anti-LKM-1) ditentukan oleh imunofluoresensi tidak langsung dan ELISA, manakala alel HLA DRβ1 (* 04) dinilai oleh urutan khusus PCR konvensional. ANA dikesan pada 41%, ASMA pada 17.4%, AMA pada 7%, LKM-1 dalam 5.8% dsDNA pada 4.6% pesakit CHC manakala HLA-DRβ1 (*04) hadir pada 3.5% pesakit, tetapi ini tidak secara signifikan dikaitkan dengan auto-antibodi ini.
Kata kunci: Auto-antibodi; HCV; hepatitis C; HLA DRβ1; imunopendafluor
RUJUKAN
Aslam,
R., Raza, S.M., Naeemi, H., Mubarak, B., Afzal, N.
& Khaliq, S. 2016. SOCS3 mRNA expression and
polymorphisms as pretreatment predictor of response to HCV genotype 3a
IFN-based treatment. Springer Plus 5(1): 1-9.
Arshad, A. & Ashfaq, U.A. 2017. Epidemiology of hepatitis C infection in
Pakistan: Current estimate and major risk factors. Critical Reviews in
Eukaryotic Gene Expression 27(1):
63-77.
Baharlou, R., Faghihi-Kashani,
A., Faraji, F., Najafi-Samei,
M., Setareh, M., Zamani, F.
& Tajik, N. 2016. HLA-DRB1 alleles of susceptibility and protection in
Iranians with autoimmune hepatitis. Human Immunology 77(4):
330-335.
Barker
Phenol-Chloroform Isoamyl Alcohol (PCI) DNA
Extraction. 1998.
Béland, K., Lapierre,
P. & Alvarez, F. 2009. Influence of genes, sex, age and environment on the
onset of autoimmune hepatitis. World Journal of Gastroenterology 15(9): 1025-1034.
Bogdanos, D.P., Mieli-Vergani, G. & Vergani,
D. 2005. Non-organ-specific autoantibodies in hepatitis C virus infection: Do
they matter? Clinical Infectious Diseases 40(4): 508-510.
Chrétien, P., Chousterman, M., Alsamad, I.A., Ozenne, V., Rosa, I., Barrault,
C., Lons, T. & Hagège,
H. 2009. Non-organ-specific autoantibodies in chronic hepatitis C patients:
association with histological activity and fibrosis. Journal of Autoimmunity 32(3-4): 201-205.
Clifford,
B.D., Donahue, D., Smith, L., Cable, E., Luttig, B., Manns, M. & Bonkovsky, H.L.
1995. High prevalence of serological markers of autoimmunity in patients with
chronic hepatitis C. Hepatology (Baltimore, Md.) 21(3): 613-619.
Czaja, A.J. & Carpenter, H.A. 2006.
Distinctive clinical phenotype and treatment outcome of type 1 autoimmune
hepatitis in the elderly. Hepatology (Baltimore,
Md.) 43(3): 532-538.
Czaja, A.J., Carpenter, H.A. & Moore,
S.B. 2006. Clinical and HLA phenotypes of type 1 autoimmune hepatitis in North
American patients outside DR3 and DR4. Liver International 26(5):
552-558.
Falleti, E., Fabris,
C., Toniutto, P., Fontanini, E., Cussigh,
A., Bitetto, D., Fornasiere,
E., Avellini, C., Minisini, R. & Pirisi, M. 2008. TGF-β1 genotypes in cirrhosis:
Relationship with the occurrence of liver cancer. Cytokine 44(2):
256-261.
Hamid,
S., Qureshi, A.R. & Kiyani, A. 1995. Is a liver
biopsy mandatoty prior to treatment for chronic
hepatitis C. In XI Annual Congress of Pak
Society Gastroenterology and GI Endoscopy. Peshawar. pp. 28-31.
Hassan,
N., Siddiqui, A.R., Abbas, Z., Hassan, S.M., Soomro,
G.B., Mubarak, M., Anis, S., Muzaffar,
R. & Zafar, M.N. 2013. Clinical profile and HLA typing of autoimmune
hepatitis from Pakistan. Hepatitis Monthly 13(12): e13598.
Hill-Burns,
E.M., Factor, S.A., Zabetian, C.P., Thomson, G. & Payami, H. 2011. Evidence for more than one
Parkinson's disease-associated variant within the HLA region. PLoS ONE 6(11): e27109.
Himoto, T. & Nishioka, M. 2013. Autoantibodies in liver disease: Important
clues for the diagnosis, disease activity and prognosis. Autoimmunity
Highlights 4(2): 39-53.
Janeway Jr., C.A., Travers, P., Walport, M. & Shlomchik, M.J.
2001. The major histocompatibility complex and its functions. In Immunobiology: The Immune System in Health and
Disease. 5th
ed. New York: Garland Science.
Kaur,
N., Minz, R.W., Anand, S., Saikia, B., Aggarwal, R., Ashim Babu, D., Thapa, R. & Chawla,
Y.K. 2014. HLA DRB1 alleles discriminate the manifestation of autoimmune
hepatitis as type 1 or type 2 in North Indian population. Journal of
Clinical and Experimental Hepatology 4(1): 14-18.
Kirdar, S., Sener,
A.G., Cengiz, M. & Aydin, N. 2016. The prevalence
of autoantibody and its relationship with genotypes of hepatitis C virus in
patients with chronic hepatitis C virus infection. APMIS 124(11): 979-984.
Kumar,
T., Ahmad, N., Hayat, M.K., Gao, B., Faisal, S., Ilahi,
N., Ali, B., Zada, S. & Sajjad,
W. 2017. Prevalence and genotypic distribution of hepatitis C Virus in Peshawar
KPK, Pakistan. HAYATI Journal of Biosciences 24(1): 22-25.
Kuniholm, M.H., Kovacs, A., Gao,
X., Xue, X., Marti, D., Thio,
C.L., Peters, M.G., Terrault, N.A., Greenblatt, R.M., Goedert, J.J., Cohen, M.H., Minkoff,
H., Gange, S.J., Anastos,
K., Fazzari, M., Harris, T.G., Young, M.A., Strickler, H.D. & Carrington, M. 2010. Specific human
leukocyte antigen class I and II alleles associated with hepatitis C virus
viremia. Hepatology (Baltimore, Md.) 51(5): 1514-1522.
Ma,
J., Liu, Y.C., Fang, Y., Cao, Y. & Liu, Z.L. 2015. TGF-β1 polymorphism
509 C>T is associated with an increased risk for hepatocellular carcinoma in
HCV-infected patients. Genetics and
Molecular Research 14(2): 4461-4468.
Metwally, K., Abdo, S.A., Badr, S., Abdurrhman, M.A., Saafan, N.K.,
Abdel-Bary, A.M. & Abbas, M.H. 2012. Serum autoantibodies
in chronic hepatitis C: Comparison with hepatitis C/Autoimmune hepatitis
overlap syndrome in Egypt. Life Science Journal 9: 1086-1091.
Muratori, L., Bogdanos,
D.P., Muratori, P., Lenzi,
M., Granito, A., Ma, Y., Mieli-Vergani,
G., Bianchi, F.B. & Vergani, D. 2005.
Susceptibility of thyroid disorder in hepatitis C. Clin. Gastroenterolog. Hepatol. 3(6):
595-603.
Pisetsky, D.S. 2016.
Anti-DNA antibodies - quintessential biomarkers of SLE. Nature Reviews
Rheumatology 12(2): 102-110.
Rao,
X., Hoof, I., van Baarle, D., Keşmir,
C. & Textor, J. 2015. HLA preferences for
conserved epitopes: A potential mechanism for hepatitis C clearance. Frontiers
in Immunology 6: 552.
Renou, C., Halfon,
P., Pol, S., Cacoub, P., Jouve,
E., Bronowicki, J.P., Arpurt,
J.P., Rifflet, H., Picon,
M., Causse, X., Canva, V.,
Denis, J., Tran, A., Bourliére, M., Ouzan, D., Pariente, A., Dantin, S., Alric, L., Cartier,
V., Reville, M. & Caillat-Zucman,
S. 2002. Histological features and HLA class II alleles in hepatitis C virus
chronically infected patients with persistently normal alanine aminotransferase
levels. Gut 51(4): 585-590.
Rosen,
H.R. 2011. Clinical practice. Chronic hepatitis C infection. The New England Journal of Medicine 364(25): 2429-2438.
Roughan, J.E., Reardon,
K.M., Cogburn, K.E., Quendler,
H., Pockros, P.J. & Law, M. 2012. Chronic
hepatitis C virus infection breaks tolerance and drives polyclonal expansion of
autoreactive B cells. Clinical and Vaccine Immunology 19(7): 1027-1037.
Scotto,
G., Fazio, V., D'Alessandro, G., Monno, L., Saracino, A., Palumbo, E. & Angarano,
G., 2003. Association between HLA class II antigens and hepatitis C virus
infection. Journal of Biological
Regulators and Homeostatic Agents 17(4): 316-321.
Shoenfeld, Y., Meroni, P.L. & Gershwin, M.E. 2013. Autoantibodies. 3rd
edition. Elsevier.
Song,
S.W., Miranda, C.J., Braun, L., Meyer, K., Frakes,
A.E., Ferraiuolo, L., Likhite,
S., Bevan, A.K., Foust, K.D., McConnell, M.J., Walker, C.M. & Kaspar, B.K. 2016. Major histocompatibility complex class I
molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic
lateral sclerosis. Nature Medicine 22(4): 397-403.
Stroffolini, T., Colloredo, G.,
Gaeta, G.B., Sonzogni, A., Angeletti,
S., Marignani, M., Pasquale, G., Venezia,
G., Craxì, A. & Almasio,
P. 2004. Does an ‘autoimmune’profile affect the
clinical profile of chronic hepatitis C? An Italian multicentre survey. Journal of Viral Hepatitis 11(3): 257-262.
Tarao, K., Rino,
Y., Ohkawa, S., Tamai, S., Miyakawa, K., Takakura, H., Endo, O., Yoshitsugu,
M., Watanabe, N. & Matsuzaki, S. 2002. Close
association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus-associated cirrhosis. Cancer 94(6): 1787-1795.
Thio, C.L., Gao, X., Goedert,
J.J., Vlahov, D., Nelson, K.E., Hilgartner,
M.W., O'Brien, S.J., Karacki, P., Astemborski,
J., Carrington, M. & Thomas, D.L. 2002. HLA-Cw*
04 and hepatitis C virus persistence. Journal of Virology 76(10):
4792-4797.
Tomer, S., Chawla, Y.K., Duseja, A. & Arora, S.K. 2016. Dominating expression of
negative regulatory factors downmodulates major
histocompatibility complex class-II expression on dendritic cells in chronic
hepatitis C infection. World Journal of Gastroenterology 22(22):
5173-5182.
Umemura, T., Katsuyama,
Y., Yoshizawa, K., Kimura, T., Joshita,
S., Komatsu, M., Matsumoto, A., Tanaka, E. & Ota, M. 2014. Human leukocyte
antigen class II haplotypes affect clinical characteristics and progression of
Type 1 autoimmune hepatitis in Japan. PLoS ONE 9(9): e109494.
Yamagiwa, S., Kamimura,
H., Takamura, M., Genda,
T., Ichida, T., Nomoto, M. & Aoyagi, Y. 2014.
Presence of antibodies against self human leukocyte
antigen class II molecules in autoimmune hepatitis. International Journal of Medical Sciences 11(9): 850-856.
*Pengarang untuk surat-menyurat;
email: romeeza.tahir@uhs.edu.pk