ABSTRACT
INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains. METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection. RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 ratio (P = 0.001). CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human/genetics , Pulmonary Surfactant-Associated Protein A/genetics , Adult , Blood Pressure , Female , Haplotypes , Hospitalization , Humans , Influenza, Human/physiopathology , Male , Mutation, Missense , Polymorphism, Single Nucleotide , Prospective Studies , Retrospective Studies , Severity of Illness IndexABSTRACT
OBJECTIVE: To investigate the prevalence of hepatitis B virus (HBV) genotypes in Spanish hepatitis B carriers, and to study the differences in epidemiological characteristics, e antigen (HBeAg) seroconversion, serum DNA viral levels (VL) and liver function alterations. METHODS: This study included 108 patients. Genotyping was carried out in 84 with the INNO-LiPA HBV genotyping assay (Innogenetics). RESULTS: There were 41 women and 67 men, with a mean age of 44.1 years. The source of transmission was family contact in 26 patients (24.1%); transfusions in 10 (9.3%); sexual promiscuity in 9 (8.3%), intravenous drug use in 3 (2.8%), health care accident in 2 (1.8%); and unknown causes in 58 (53.7%). Forty patients had chronic hepatitis and 68 (63%) were healthy carriers. The time of evolution of the infection was known in only in 45 patients, and was over 10 years in 42 of them. One hundred patients (92.6%) were HbeAg-negative and 90 (83.3%) had detectable viral DNA. Genotype A was present in 46 (54.8%), D in 20 (23.8%), F in 2 (2,4%), C in 1 (1.2%), A-G coinfection in 7 (8.3%), A-D in 4 (4.8%), D-G in 2 (2,4%), A-C in 1 (1.2%), and A-D-G in 1 (1.2%). There were no significant differences between genotypes. A trend towards an association was found between VL Subject(s)
Hepatitis B virus/genetics
, Hepatitis B, Chronic/epidemiology
, Adult
, Atlantic Islands/epidemiology
, Carrier State
, Female
, Genotype
, Hepatitis B e Antigens/blood
, Hepatitis B virus/isolation & purification
, Hepatitis B, Chronic/virology
, Humans
, Male
, Middle Aged
, Prevalence
, Viral Load
ABSTRACT
Objetivo. Conocer la distribución de genotipos del virus de la hepatitis B (VHB) de pacientes españoles portadores crónicos y su relación con las características epidemiológicas, la presencia de antígeno e, el nivel sérico del ADN viral (CV) y la alteración de la función hepática. Métodos. Se estudiaron 108 pacientes. El genotipo se realizó en 84 mediante INNO-LiPA HBV Genotyping-Innogenetics. Resultados. De los pacientes, 41 fueron mujeres y 67 hombres, con una edad media de 44,1 años. Las fuentes de transmisión fueron: contacto familiar, 26 pacientes (24,1%); transfusiones, 10 (9,3%); promiscuidad sexual, 9 (8,3%); adicción a drogas parenterales, 3 (2,8%); accidente sanitario, 2 (1,8%) y en 58 (53,7%) se desconocía. Cuarenta pacientes (37%) presentaron una hepatitis crónica (HC) y 68 (63%) eran portadores asintomáticos. Sólo en 45 pacientes se conocía el tiempo de evolución de la infección y en 42 fue mayor de 10 años. Cien pacientes (92,6%) presentaron antígeno e-negativo y 90 (83,3%) tuvieron ADN viral detectable. La distribución de genotipos fue: A, 46 (54,8%); D, 20 (23,8%); F, 2 (2,4%); C, 1 (1,2%), coinfección A-G, 7 (8,3%); A-D, 4 (4,8%); D-G, 2 (2,4%); A-C, 1 (1,2%) y A-D-G, 1 (1,2%). No se observaron diferencias significativas entre genotipos. Se observó una tendencia en el genotipo A a presentar HC cuando la CV ≤ 10 5 copias/ml (28,9% de los casos) frente al genotipo D (7,7%) (p no significativa). Conclusiones. En nuestra área predomina el genotipo A, D y las coinfecciones con G. Observamos una tendencia del genotipo A a producir una mayor actividad inflamatoria cuando la CV ≤ 10 5 copias/ml (AU)
Objective. To investigate the prevalence of hepatitis B virus (HBV) genotypes in Spanish hepatitis B carriers, and to study the differences in epidemiological characteristics, e antigen (HBeAg) seroconversion, serum DNA viral levels (VL) and liver function alterations. Methods. This study included 108 patients. Genotyping was carried out in 84 with the INNO-LiPA HBV genotyping assay (Innogenetics).Results. There were 41 women and 67 men, with a mean age of 44.1 years. The source of transmission was family contact in 26 patients (24.1%); transfusions in 10 (9.3%); sexual promiscuity in 9 (8.3%), intravenous drug use in 3 (2.8%), health care accident in 2 (1.8%); and unknown causes in 58 (53.7%). Forty patients had chronic hepatitis and 68 (63%) were healthy carriers. The time of evolution of the infection was known in only in 45 patients, and was over 10 years in 42 of them. One hundred patients (92.6%) were HbeAg-negative and 90 (83.3%) had detectable viral DNA. Genotype A was present in 46 (54.8%), D in 20 (23.8%), F in 2 (2,4%), C in 1 (1.2%), A-G coinfection in 7 (8.3%), A-D in 4 (4.8%), D-G in 2 (2,4%), A-C in 1 (1.2%), and A-D-G in 1 (1.2%). There were no significant differences between genotypes. A trend towards an association was found between VL ≤ 10 5 copies/mL and the presence of chronic hepatitis in genotype A (28.9%) as opposed to genotype D (7.7%) (p non significant). Conclusions. HBV genotypes A and D, and coinfections with G are predominant in our area. Genotype A showed a tendency to produce greater inflammatory activity when VL was ≤ 10 5 copies/ml (AU)
