Journal d'immunobiologie

Liver cancer is the 6th most common cancer and 2nd leading cause of cancer-related mortality. In order to improve patient survival early tumor detection is required and this necessitates accurate screening of at risk individuals. In this article we concisely review the methodologies employed for Hepatocellular Carcinoma (HCC) surveillance and how their use has evolved over the last three decades. We focus attention to serum biomarkers, particularly alpha-fetoprotein. We propose that by using an increasingly sophisticated approach to assess dynamic rates of change in biomarkers tailored to individual patients that screening accuracy may be improved. Additional improvements may also be possible by the incorporation of patient clinical data into such personalised screening assessments. These possibilities may hold the promise of improving cancer detection and early curative therapy for the increasing worldwide population at risk of HCC development.

Mast cells (MCs) are tissue resident immune cells that are best known for their roles in allergic and inflammatory diseases. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the most common targets of drug therapy. Neurokinin 1 receptor (NK-1R) is expressed on MCs and contributes to IgE and non-IgE-mediated responses in mice. Although NK-1R antagonists are highly effective in modulating experimental allergic and inflammatory responses in mice they lack efficacy in humans. This article reviews recent findings that demonstrate that while neuropeptides (NPs) activate murine MCs via NK-1R and Mas related G protein coupled receptor B2 (MrgprB2), they activate human MCs via Mas-related G protein coupled receptor X2 (MRGPRX2). Interestingly, conventional NK-1R antagonists have off-target activity against mouse MrgprB2 but not human MRGPRX2. These findings suggest that the failure to translate studies with NK-1R antagonists from in vivo mouse studies to the clinic likely reflects their lack of effect on human MRGPRX2. A unique feature of MRGPRX2 that distinguishes it from other GPCRs is that it is activated by a diverse group of ligands that include; neuropeptides, cysteine proteases, antimicrobial peptides and cationic proteins released from activated eosinophils and neutrophils. Thus, the development of small molecule MRGPRX2-specific antagonists or neutralizing antibodies may provide new targets for the treatment of MC-mediated allergic and inflammatory diseases.

Belimumab neutralizes the soluble form of B-cell activating factor and is FDA-approved for treating Systemic Lupus Erythematosus (SLE). In this retrospective analysis 16 female SLE patients had been treated with belimumab according to FDA guidelines along with any immunosuppressive drugs or antimalarial drugs they had previously been prescribed, in addition to prednisone. Thirteen of 16 patients presented with serologic evidence of positive anti-nuclear antibody titer while several other SLE patients also had clinical evidence of secondary Sjogren’s Syndrome (2°SS), the latter supported by sicca symptoms and positive anti-Sjogren’s-syndrome-related antigen A antibody titer. Changes in the SLE symptoms after belimumab therapy was assessed by the recipient’s responses on the Short Form-36 questionnaire. Ten of the 16 SLE patients reported a decrease in arthralgias or in symptoms of arthritis while fatigue was reduced in 9/16 patients. However, SLE patients with sicca symptoms failed to show any change in the Short Form-36 score after treatment with belimumab. In conclusion, although the results in this small cohort study supported the use of belimumab as an adjunctive therapy for SLE, sicca symptoms associated with 2°SS did not appear to respond to belimumab.