THE HLA-G 14-BASE PAIR DELETION ALLELE AND THE DELETION/DELETION GENOTYPE ARE ASSOCIATED WITH PERSISTENT HBE ANTIGENEMIA IN CHRONIC HEPATIS B INFECTION

• Published in: Human immunology 2017-02, Vol.78 (2), p.166-171
• Main Authors: da Costa Ferreira, Sandro, Gama Florêncio Chachá, Silvana, Fernandes Souza, Fernanda, Corrêa Teixeira, Andreza, de Carvalho Santana, Rodrigo, Hassan Saloun Deghaide, Neifi, Rodrigues, Sandra, Marano, Leonardo A, Teixeira Mendes-Junior, Celso, Naira Zambelli Ramalho, Leandra, Zucoloto, Sérgio, Antônio Donadi, Eduardo, de Lourdes Candolo Martinelli, Ana
• Format: Article
• Language: English
• Subjects: 14 bp-insertion/deletion (I/D); Adolescent; Adult; Aged; Allergy and Immunology; Antigens, Viral - metabolism; Carrier State; Child; Chronic hepatitis B; Female; Follow-Up Studies; Gene Frequency; Genotype; HBeAg-positive; Hepatitis B virus - physiology; Hepatitis B, Chronic - genetics; HLA-G; HLA-G Antigens - genetics; Humans; INDEL Mutation - genetics; Male; Middle Aged; Polymorphism, Single Nucleotide; Viremia - genetics; Young Adult
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2016.12.011

Abstract Background and aims HLA-G has well-recognized immunomodulatory properties, and this molecule is frequently expressed in the livers of hepatitis B virus (HBV)-infected patients. Because the HLA-G 14 bp-insertion/deletion polymorphism (rs371194629) has been associated with the magnitude of HLA-G expression, we evaluated this polymorphism in the recognized evolutionary forms of chronic HBV infection . Methods : We studied 196 chronic HBV-infected patients (118 HBeAg-negative chronic hepatitis, 53 HBeAg-positive chronic hepatitis and 25 inactive carriers exhibiting low levels of serum HBVDNA and persistently normal ALT levels), and 202 healthy individuals. Chronic hepatitis HLA-G typing was performed using PCR-amplified DNA hybridized with specific primers. R esults: The frequencies of the insertion/deletion alleles and genotypes were very similar in patients and controls. After patient stratification according to the evolutionary form of the chronic HBV infection, the frequencies of the deletion allele ( P =0.0460; OR=1.26; 95%CI=1.01-1.45) and of the deletion/deletion genotype ( P =0.0356; OR=2.08; 95%CI=1.05-4.09) were overrepresented in HBeAg-positive patients when compared to HBeAg-negative patients. No differences were observed when HBV inactive carriers were compared to HBeAg-negative chronic hepatitis patients. Conclusions : Because the 14-bp deletion allele has been associated with increased HLA-G production and because HLA-G may down regulate the cytotoxic activity of TCD8 and NK cells, patients exhibiting the 14-bp deletion allele at single or double doses are at increased risk for developing chronic forms of HBV associated with persistent viremia and worse prognoses.