The concept of personalised medicine is not new

The concept of personalised medicine is not new, however the rapid advances in technologies such as genomics, transcriptomics and metabolomics for the analysis of blood and tissue has opened up new horizons in this area in the last few years (). As outlined above, the range of biotherapeutics now available for the treatment of RMD is extensive, and the key challenge for translational scientists is to create and validate a strategic approach to the treatment of RA (). Early diagnosis is only the first step, subsets of patients need to be stratified by a reliable biomarker, or more likely a combination of biomarkers, that will allow treatment decisions to follow an algorithm defined on a pathological basis, similar to that which has been developed for the treatment of breast cancer (). For example, it pkm2 has been suggested that B-lymphocyte infiltrates on immunohistochemistry of synovial tissue may be a biomarker of response to therapy with rituximab in RA patients. In order to gauge the success or failure of treatments in RMD, following early diagnosis and strategic patient stratification, we need reliable and feasible outcome measures. A multidisciplinary group of researchers have attempted to refine and develop Outcome MEasures in Rheumatoid Arthritis Clinical Trials (OMERACT) using a progressive and well-defined methodology, combining literature review and consensus over the past 20years (). Initially, the focus of the group was on RA alone; however over time, they have extended this approach to most RMD and included clinicians, nurses, industry partners and, possibly most importantly, the patients themselves. This group was the first to identify and validate a synovial tissue biomarker – CD68 – to reflect synovial pathologic responses in clinical trials (). It may be relatively easy to define the patient who achieves complete remission – no clinical signs or symptoms of disease activity and no residual damage – but this is unfortunately quite rare. According to the most recent studies examining the new EULAR/ACR remission criteria, complete remission may apply to only 10% or less of treated patients ().
In this issue of , Christian Münz and colleagues show that Epstein–Barr Virus (EBV) induces an accumulation of membranes related to the cellular autophagy pathway, and that an autophagic marker can be found in EBV particles (). This suggests that autophagic membranes participate in generation of the viral envelope. This suggests new avenues for inhibiting gamma-herpesvirus formation and the possibility of antigenicity from autophagic markers on virions. To understand the importance of this finding, we need to examine autophagy and its relationship to viruses.
Both host and viral factors are associated with HIV-1 susceptibility and disease progression. Host factors can typically be divided into three categories (): 1) genes encoding cell-surface receptors or ligands for these proteins, including the classic CCR5 32-bp deletion; 2) genes within the human leukocyte antigens (HLA) that regulate host responses to infection; and 3) other cytokine and immune response genes, including the homozygosity at position −308 in the TNF-alpha promoter. More recently genome-wide association studies (GWAS) have detected new genetic factors associated with HIV-1 infection (). In addition, an extensive array of host physiological responses have been assessed, including MCP-1 (CCL2) (). In relation to HIV-1 susceptibility, the co-receptors CXCR4 and CCR5 are classically linked to infection of T cells and cells of the monocyte–macrophage lineage (MML), respectively. CCR5-utilizing viruses are the major type of virus transmitted therefore MML cells have been thought to contribute to early disease progression. More recently it has been demonstrated that T lymphocytes may also be a major vehicle for HIV-1 transmission. Transmitted viruses preferentially use CCR5 as a co-receptor, require high levels of CD4, and are able to replicate efficiently in primary CD4+ T-cells, suggesting a CCR5-utilizing T-tropic viral phenotype (). Subsequently, these founder viruses can infect MML cells, resulting in the development of a wider target cell population that expresses higher levels of CCR5 than T cells (). Although in the classical sense, co-receptor utilization remains the most important factor in HIV-1 susceptibility, a number of other host factors are currently under investigation that also appear to play a role in cellular susceptibility. Often these host factors interact with viral proteins thereby affecting the efficiency of viral infection.