Inborn Errors of Immunity and Cancer

Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders characterized by a defect in the function of at least one, and often more, components of the immune system. The aim of this narrative review is to discuss the epidemiology, the pathogenesis and the correct management of tumours in patients with IEI. PubMed was used to search for all of the studies published over the last 20 years using the keywords: “inborn errors of immunity” or “primary immunodeficiency” and “cancer” or “tumour” or “malignancy”. Literature analysis showed that the overall risk for cancer in children with IEI ranges from 4 to 25%. Several factors, namely, age of the patient, viral infection status and IEI type can influence the development of different cancer types. The knowledge of a specific tumour risk in the presence of IEI highlights the importance of a synergistic effort by immunologists and oncologists in tracking down the potential development of cancer in known IEI patients, as well as an underlying IEI in patients with newly diagnosed cancers. In the current genomic era, the creation of an international registry of IEI cases integrated with malignancies occurrence information is fundamental to optimizing the diagnostic process and to evaluating the outcomes of new therapeutic options, with the hope to obtain a better prognosis for these patients.

Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression

Current knowledge on the biology of squamous cell vulvar carcinoma (VSCC) is limited. We aimed to identify protein markers of VSCC tumors that would permit to stratify patients by progression risk. Early-stage tumors from patients who progressed (progVSCC) and from those who were disease-free (d-fVSCC) during follow-up, along with normal vulvar tissues were examined by mass spectrometry-based proteomics. Differentially expressed proteins (DEPs) were then verified in solid tissues and blood samples of patients with VSCC tumors and vulvar premalignant lesions. In progVSCC vs. d-fVSCC tumors, the immune response was the most over-represented Gene Ontology category for the identified DEPs. Pathway profiling suggested bacterial infections to be linked to aggressive VSCC phenotypes. High Mobility Group AT-Hook 2 (HMGA2) and Proteinase 3 (PRTN3) were revealed as proteins predicting VSCC progression. HMGA2 and PRTN3 abundances are associated with an aggressive phenotype, and hold promise as markers for VSCC patient stratification. It appears that vulvovaginal microflora disturbances trigger an inflammatory response contributing to cancer progression, suggesting that bacterial rather than viral infection status should be considered in the development of targeted therapies in VSCC.

Understanding ‘risk’ in families living with mixed blood-borne viral infection status: The doing and undoing of ‘difference’

‘Risk’ has long been at the centre of expert and popular perceptions of transmissible and stigmatised blood-borne viral infections, such as HIV and viral hepatitis. There is a substantial body of research on transmission risk among couples with mixed viral infection status (serodiscordance). But we know very little about how families affected by HIV and viral hepatitis engage with understandings of infectiousness and how these shape family relationships in different ways. Guided by cultural theories of risk that build on Mary Douglas’ work, we draw on qualitative interviews to explore the ‘performativity’ of risk in serodiscordant families in Australia. We show how the ‘doing’ of risk could be constitutive of difference, which unsettled the family connection or deepened existing fault lines. Conversely, the ‘undoing’ of risk enabled the preservation of the family bond by rejecting difference and reframing risk as an external threat to the family in the form of stigma. We conclude that risk in the context of serodiscordant families had relational implications far beyond viral transmission and consider what our findings might mean for service provision and health promotion campaigns related to blood-borne viruses.

Acute Abdomen: A Rare Case of Ruptured Hepatocellular Carcinoma

Spontaneous ruptures of hepatocellular carcinoma (HCC) are rare. Nevertheless they may lead to difficult decisions in the emergency situation. The acute therapies include conservative treatment, transarterial embolization and surgery. Curative treatment of HCC can be achieved by liver resection solely. The decision-making depends on prognostic patient’s factors, such as hepatic viral infection status, Child-Pugh grade, liver cirrhosis and number of tumors. In this case transarterial embolization was preferable as a bridging therapy prior to further diagnostics and therapy, to lower the perioperative morbidity and mortality. The therapy of these cases needs an interdisciplinary approach to choose the best possible procedure in each case.

Impact of Desensitization on Antiviral Immunity in HLA-Sensitized Kidney Transplant Recipients

Viral infections represent significant morbidity and mortality factors in kidney transplant recipients, with CMV, EBV, and BKV infections being most common. Desensitization (DES) with IVIg and rituximab with/without plasma exchange followed by kidney transplantation with alemtuzumab induction increased successful transplant rates in HLA-sensitized patients but may represent an increased risk for viral infections due to severe lymphocyte depletion. Here, we report on the posttransplant viral infection status in 372 DES versus 538 non-DES patients. CMV and EBV viremia were significantly lower in DES patients, while BKV viremia was similar. This trend was observed primarily in CMV sero(−), EBV sero(+), and sero(−) patients. No patient developed PTLD. The incidence of BKAN, allograft, and patient survival was similar in both groups. These viral infections were not associated with subsequent allograft rejection which occurred within 6 months after the infection.Conclusions.The IVIg + rituximab desensitization combined with alemtuzumab induction with triple immunosuppression maintenance does not increase the risk for CMV, EBV, and BKV infections. Possible factors include, in addition to posttransplant antiviral prophylaxis and PCR monitoring, presence of memory T cells and antibodies specific to CMV and likely EBV, NK cell-mediated ADCC despite lymphocyte depletion, elimination of EBV and CMV reservoirs by rituximab and alemtuzumab, and use of IVIg with antiviral properties.

First Report of Grapevine redglobe virus (GRGV) in Grapevine in France

The isometric virus Grapevine redglobe virus (GRGV), was first described on grapevine cv. Red Globe in southern Italy in 2000 (3) and later in Greece and California. GRGV belongs to the genus Maculavirus in the family Tymoviridae. These viruses are thought to be disseminated through propagation and grafting, as no vectors or seed transmission are known to date. A partial sequence (2,006 nucleotides [nt]) encompassing the 3′ end of the replicase, the coat protein, and P17 genes, was obtained in 2003 (1). GRGV infections are apparently symptomless (2). In 2014, GRGV was identified by Illumina sequencing of total RNAs extracted from a Vitis vinifera cv. Cabernet franc (CF) vine grafted onto Gravesac in a vineyard of the Bordeaux region in France. This Cabernet franc plant displayed fanleaf-like degeneration symptoms associated with Tomato black ring virus (TBRV) infection. It had been collected in 2010 and maintained since in a greenhouse. The partial contigs assembled from the Illumina reads (552 and 430 nt, both in the putative replicase gene, KM491303 and KM491304) showed 85.9 and 86.3% nt identity with the partial sequence of a GRGV Italian isolate (AF521577), respectively. Total RNA extracts from leaves of 18 plants of cv. Cabernet franc from the same plot, collected in 2014, were analyzed by RT-PCR using specific primers RG-CF-F1 (5′-GAATTCGCTGTCGGCCACTC-3′) and RG-CF-R1 (5′-AGTGAGAGGAGAGATTCCATC-3′) designed on the basis of the alignment of the partial sequences of GRGV-CF and the Italian isolate (AF521577). Fifteen (83%) of the plants gave strong positive amplification for GRGV. Given the mixed viral infection status of these vines, it was not possible to associate a specific symptomatology with the presence of GRGV. Two RT-PCR amplicons were directly sequenced and showed 91.5 and 91.7% identities, respectively, with the reference GRGV-CF sequence. To our knowledge, this is the first report of GRGV in France. Further studies will be necessary to determine the prevalence of GRGV in the French vineyards and varieties, including rootstocks, and its possible threat to the grapevine industry. Studies are also needed to assess the pathogenicity of GRGV. Similarly to its close relative, Grapevine fleck virus, does it induce latent or semi-latent infections in Vitis vinifera and rootstock hybrids, influencing vigor, rooting ability, and graft compatibility? References: (1) N. Abou Ghanem-Sabanadzovic et al. Virus Genes 27:11, 2003. (2) G. P. Martelli et al. Arch. Virol. 147:1847, 2002. (3) S. Sabanadzovic et al. Arch. Virol. 145:553, 2000.