Anti-HAVCR1 monoclonal antibody, clone FQS7494(3)

Introduction and aim. HAVCR1 protein is the cellular receptor for hepatitis A virus (HAV). Genetic polymorphism in this gene may alter the outcome of HAV infection. In a previous study, a 6-amino acid insertion (157insMTTTVP) in HAVCR1 gene was associated with more severe disease. We decided to investigate this association further. Material and methods. We sequenced exon 4 of the HAVCR1 gene in patients with clinical hepatitis A attending our institution, and a group of healthy controls in a disease-endemic setting in India. Frequencies of different haplotypes of a genomic region with two overlapping insertion-deletion polymorphisms (indels; rs141023871 and rs139041445) were compared between patients and controls, as well as between patients with and without a severe form of disease (liver failure). Results. The gene had three haplotypes in the region of interest - a short form, an intermediate-form with a 5-amino acid 157insMTTVP insertion and a long-form with a 6-amino acid 157insMTTTVP insertion. The allele frequency (29/150 [19%] vs. 43/146 [29%]; p = ns) and haplotype frequency (29/75 [39%] vs. 39/73 [53%]; p = ns) of the 157insMTTTVP variant were similar in hepatitis A patients and healthy controls (30%). Further, the allele frequency (12/58 [21%] vs. 17/92 [18%]; p = ns) and haplotype frequency (12/29 [41%] vs. 17/46 [37%]; p = ns) of the longest variant were also similar in patients with severe and mild disease. Discussion. In the study population, the 157insMTTTVP variant of HAVCR1 gene was not associated with more severe outcome of HAV infection. Further studies in other populations around the world are needed to assess the relation of this genetic variation with disease outcome.

P>The aim of this study was to assess gene expression levels of four biomarker candidates [lipocalin 2 (LCN2), the kidney injury molecule 1 (HAVCR1), netrin 1, and the cysteine-rich, angiogenic inducer, 61] in the tubulointerstitial and the glomerular compartment of zero-hour kidney biopsies in order to predict developing delayed graft function (DGF). Thirty-four needle kidney biopsy samples of deceased donors were manually microdissected. Relative gene expression levels were determined by real-time RT-PCR. For the validation of the biomarker candidates, we calculated a mixed model comparing kidneys with DGF, primary function and control samples from the healthy parts of tumor nephrectomies. Significant biomarker candidates were analyzed together with donor age in multivariable regression models to determine the prognostic value. Expression levels of LCN2 and HAVCR1 in the tubulointerstitium were significantly upregulated in the DGF group (LCN2: fold change = 3.78, P = 0.031 and HAVCR1: fold change = 3.44, P = 0.010). Odds ratios of both genes could not reach significance in the multivariable model together with donor age. The area under the curve of the receiver operating characteristic ranges between 0.75 and 0.83. LCN2 and HAVCR1 gene expression levels in zero-hour biopsies show potential to act as early biomarkers for DGF.