Anti-PRF1 monoclonal antibody, clone C-E59 [FITC]

Innate immunity plays an important role in the pathogenesis of primary biliary cirrhosis (PBC) that needs to be characterized. Levels and clinical relationship of Fc gamma receptor III-A (Fc gamma R3A), tyrosine kinase binding protein (TYROBP) and perforin-1 (PRF1), important genes for nature killer (NK) cells, were analyzed in PBC patients. The purpose of this study was to explore the expression levels of the above-mentioned genes in peripheral blood mononuclear cells (PBMCs) from PBC patients. A total of 102 PBC patients and 85 healthy controls (HC) were recruited. The relative levels of FC gamma R3A, TYROBP, and PRF1 mRNA transcripts in PBMCs were determined by RT-PCR. The percentages of peripheral blood NK, natural killer T (NKT), FC gamma R3A(+) or PRF1(+) NK cells and PRF1(+) NKT cells in PBC patients and HC were also characterized by flow cytometry analysis. The potential associations of the percentages of NK and NKT cells with clinical indexes were analyzed. The relative levels of FC gamma R3A, TYROBP, and PRF1 mRNA transcripts and the percentages of PRF1(+) NK and NKT cells in PBC patients were significantly higher than that in HC. Moreover, the percentages of PRF1-expressing NK and NKT cells in PBC patients were negatively associated with the levels of serum gamma-glutamyltransferase (GGT) and Mayo risk scores, and the relative levels of FC gamma R3A expression in NK cells of PBC patients were positively associated with the levels of serum GGT. FC gamma R3A and PRF1 may participate in the pathogenesis and progression of PBC.

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, multi-factorial disease sustained by environmental and genetic factors. These seem to be necessary but not sufficient in the disease development, nonetheless they can be responsible of different clinical pictures and response to therapy, and they can represent potential therapeutic targets. Several genes have been indicated so far in the pathogenesis of RA. The most important region is the Human Leukocyte Antigen (HLA) that contributes to approximately half of the genetic susceptibility for RA. The association seems to be stronger or specific for anti-citrullinated protein antibodies positive disease. Several alleles in the epitope-recognition part of the HLA molecule that show the highest association with RA susceptibility, also share a common string of amminoacid residues (the so-called shared-epitope hypothesis). Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4. Other polymorphisms seem to be responsible for more aggressive disease phenotype such as those located at TNF, IL-1, IL-6, IL-4, IL-5, OPN, PRF1. However, still nowadays, the genetic background of RA remains to be clearly depicted, and the efforts in the post-genomic era can bring to an estimation of the real likelihood of the genetic effect on RA. Finally, the discovery of new genes associated with the disease can be relevant in finding potential biomarkers, potentially useful in disease diagnosis and treatment. (C) 2011 Elsevier B.V. All rights reserved.