A Rare Case of Atypical Hemolytic Uremic Syndrome (aHUS) Precipitated by Dengue and the Treatment Landscape in Singapore.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by uncontrolled complement activation due to complement dysregulation. It is often triggered by precipitating events such as infections, inflammation, pregnancy, or medications. Dengue, an endemic viral infection in Southeast Asia, can activate the complement pathway, thereby triggering aHUS in genetically susceptible individuals. Here, we present the case of a 33-year-old male who presented with Dengue fever and subsequently developed aHUS. Plasma exchange (PLEX) successfully normalized his neurological status and hematological parameters. Although his renal function improved, it failed to normalize. Eculizumab, a monoclonal antibody that inhibits C5, was administered for a total of six months. The treatment was successfully discontinued without evidence of relapse after six months of follow-up. This case report demonstrates the safety of discontinuing eculizumab in patients who do not possess pathogenic mutations or variants in complement factors.

Hepatitis E in Singapore: A Case-Series and Viral Phylodynamics Study.

AbstractThe incidence of hepatitis E in Singapore appears to be increasing. A retrospective case-series study of patients diagnosed with hepatitis E in a tertiary hospital from 2009 to 2013 was conducted. Of 16 cases, eight (50%) were solid-organ transplant recipients (SOTRs), and 14 (88%) were found infected by genotype 3 hepatitis E virus (HEV-3). Bayesian inferences based on HEV subgenomic sequences from seven cases suggest that HEV-3 strains were introduced to Singapore as two principal lineages. Within limitations of the study, it can be inferred that one lineage, in the 3efg clade, emerged about 83 years ago, probably originating from Japan, whereas the other, in the 3abchij clade, emerged about 40 years ago, from the United States. Establishment and subsequent transmissions of strains from these two lineages likely contribute to the current endemicity of hepatitis E in Singapore.

CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes.

Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated ß2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases.

A review of monoclonal antibody therapies in lymphoma.

Monoclonal antibodies (moAb) represent a novel way of delivering therapy through specific target antigens expressed on lymphoma cells and minimizes the collateral damage that is common with conventional chemotherapy. The paradigm of this approach is the targeting of CD20 by rituximab. Since its FDA approval in 1997, rituximab has become the standard of care in almost every line of therapy in most B-cell lymphomas. This review will briefly highlight some of the key rituximab trials while looking more closely at the evidence that is bringing other antibodies, including next generation anti-CD20 moAbs, and anti-CD30 moAbs, among others to the forefront of lymphoma therapy.

Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who Regularly Consumes Camel Meat and Milk.

There have been increasing reports of food-borne zoonotic transmission of hepatitis E virus (HEV) genotype 3, which causes chronic infections in immunosuppressed patients. We performed phylogenetic analyses of the HEV sequence (partial and full-length) from 1 patient from the Middle East who underwent liver transplantation, and compared it with other orthohepevirus A sequences. We found the patient to be infected by camelid HEV. This patient regularly consumed camel meat and milk, therefore camelid HEV, which is genotype 7, might infect human beings. Our finding links consumption of camel-derived food products to post-transplantation hepatitis E, which, if detected at early stages, can be cured with antiviral therapy and reduced administration of immunosuppressive agents.