Michael Osthoff1, Elizabeth Irungu2, Kenneth Ngure3, Nelly Mugo4, Katherine K Thomas5, Jared M Baeten6, Damon P Eisen7. 1. Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia. 2. Kenyatta National Hospital, Nairobi, Kenya. 3. Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya; Department of Global Health, University of Washington, Seattle, WA, USA. 4. Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. 5. Department of Epidemiology, University of Washington, Seattle, WA, USA. 6. Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. 7. Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia. Electronic address: Damon.Eisen@mh.org.au.
Abstract
BACKGROUND: Host genetics appear to be an important factor in the failure to generate a protective immune response after hepatitis B (HBV) vaccination. Mannose-binding lectin (MBL) and ficolin-2 (FCN2), two pattern recognition receptors of the lectin pathway of complement, influence the clinical outcome of HBV, and MBL deficiency has been shown to augment the humoral response to HBV vaccination in several experimental models. Here, we investigated the association of MBL and FCN2 with the humoral response to HBV vaccination in a candidate gene and functional study. PATIENTS AND METHODS: A post hoc analysis of a prospective, interventional HBV vaccination study among human immunodeficiency virus type 1 (HIV-1) uninfected individuals in Kenya was conducted. Serum levels and polymorphisms of MBL and FCN2 were analysed in relation to the immune response to HBV vaccination. RESULTS: Protective hepatitis B surface antibody levels (≥ 10 mI U/mL) were evident in 251/293 (85.7%) individuals. Median MBL and FCN2 levels were similar in responders vs. non-responders with a weak trend towards lower median MBL levels in non-responders (1.0 vs. 1.6μg/mL, p=0.1). Similarly, there was no difference in four MBL and six FCN2 polymorphisms analysed in the two groups with the exception of an increased frequency of a homozygous MBL codon 57 mutation in non-responders (4 (9.5%) vs. 8 (3.2%), p=0.05) corresponding to lower MBL levels. Results were similar after adjusting for age and sex. CONCLUSIONS: Our study does not support a prominent role of the lectin pathway of complement in general and MBL and FCN2 in particular in the humoral immune response to HBV vaccination in African adults. Crown
BACKGROUND: Host genetics appear to be an important factor in the failure to generate a protective immune response after hepatitis B (HBV) vaccination. Mannose-binding lectin (MBL) and ficolin-2 (FCN2), two pattern recognition receptors of the lectin pathway of complement, influence the clinical outcome of HBV, and MBL deficiency has been shown to augment the humoral response to HBV vaccination in several experimental models. Here, we investigated the association of MBL and FCN2 with the humoral response to HBV vaccination in a candidate gene and functional study. PATIENTS AND METHODS: A post hoc analysis of a prospective, interventional HBV vaccination study among humanimmunodeficiency virus type 1 (HIV-1) uninfected individuals in Kenya was conducted. Serum levels and polymorphisms of MBL and FCN2 were analysed in relation to the immune response to HBV vaccination. RESULTS: Protective hepatitis B surface antibody levels (≥ 10 mI U/mL) were evident in 251/293 (85.7%) individuals. Median MBL and FCN2 levels were similar in responders vs. non-responders with a weak trend towards lower median MBL levels in non-responders (1.0 vs. 1.6μg/mL, p=0.1). Similarly, there was no difference in four MBL and six FCN2 polymorphisms analysed in the two groups with the exception of an increased frequency of a homozygous MBL codon 57 mutation in non-responders (4 (9.5%) vs. 8 (3.2%), p=0.05) corresponding to lower MBL levels. Results were similar after adjusting for age and sex. CONCLUSIONS: Our study does not support a prominent role of the lectin pathway of complement in general and MBL and FCN2 in particular in the humoral immune response to HBV vaccination in African adults. Crown
Authors: David C Kilpatrick; Anna St Swierzko; Misao Matsushita; Iwona Domzalska-Popadiuk; Monika Borkowska-Klos; Jerzy Szczapa; Maciej Cedzynski Journal: Hum Immunol Date: 2013-04-22 Impact factor: 2.850
Authors: Kelli K Ryckman; Katherine Fielding; Adrian V Hill; Maimuna Mendy; Pura Rayco-Solon; Giorgio Sirugo; Marianne A van der Sande; Pauline Waight; Hilton C Whittle; Andrew J Hall; Scott M Williams; Branwen J Hennig Journal: PLoS One Date: 2010-08-18 Impact factor: 3.240
Authors: Tong V Hoang; Nguyen L Toan; Le H Song; Eman Abou Ouf; C-Thomas Bock; Peter G Kremsner; Jürgen F J Kun; T P Velavan Journal: PLoS One Date: 2011-11-22 Impact factor: 3.240
Authors: Helle R Juul-Madsen; Liselotte R Norup; Poul H Jørgensen; Kurt J Handberg; Eva Wattrang; Tina S Dalgaard Journal: Vaccine Date: 2011-10-18 Impact factor: 3.641
Authors: Kirsi Gröndahl-Yli-Hannuksela; Juho Vuononvirta; Ville Peltola; Jussi Mertsola; Qiushui He Journal: PLoS One Date: 2014-02-18 Impact factor: 3.240
Authors: Rutendo B L Zinyama-Gutsire; Charles Chasela; Per Kallestrup; Simbarashe Rusakaniko; Michael Christiansen; Bernard Ngara; Exnevia Gomo; Henrik Ullum; Christian Erikstrup; Hans O Madsen; Babill Stray-Pedersen; Peter Garred; Takafira Mduluza Journal: OMICS Date: 2015-09