A Novel Engineering Cell Therapy Platform Mimicking the Immune Thrombocytopenia-Derived Platelets to Inhibit Cytokine Storm in Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a common and highly fatal hyperinflammatory syndrome characterized by the aberrant activation of macrophages. To date, there is a lack of targeted therapies for HLH. It is validated that macrophages in HLH efficiently phagocytose anti-CD41-platelets (anti-CD41-PLTs) from immune thrombocytopenia (ITP) patients in previous research. Hence, the pathological mechanisms of ITP are mimicked and anti-CD41-PLTs are utilized to load the macrophage-toxic drug VP16 to construct macrophage-targetable engineered platelets anti-CD41-PLT-VP16, which is a novel targeted therapy against HLH. Both in vitro and in vivo studies demonstrate that anti-CD41-PLT-VP16 has excellent targeting and pro-macrophage apoptotic effects. In HLH model mice, anti-CD41-PLT-VP16 prevents hemophagocytosis and inhibits the cytokine storm. Mechanistic studies reveal that anti-CD41-PLT-VP16 increases the cytotoxicity of VP16, facilitating precise intervention in macrophages. Furthermore, it operates as a strategic "besieger" in diminishing hyperinflammation syndrome, which can indirectly prevent the abnormal activation of T cells and NK cells and reduce the Ab-dependent cell-mediated cytotoxicity effect. The first platelet-based clinical trial is ongoing. The results show that after treatment with anti-CD41-PLT-VP16, HLH patients have a threefold increase in the overall response rate compared to patients receiving conventional chemotherapy. In conclusion, anti-CD41-PLT-VP16 provides a general insight into hyperinflammation syndrome and offers a novel clinical therapeutic strategy for HLH.

Use of ixekizumab in an HIV-positive patient with psoriatic arthritis.

Psoriasis is a chronic immune-mediated disease of the skin. The incidence of psoriasis among people living with HIV (PLHIV) is higher than that in the general population. The mechanism is complex, the manifestations are varied, and the treatment is difficult. Biotherapy has greatly alleviated psoriasis, but clinical trials often exclude PLHIV, and evidence is limited to case reports. Here, we report a man living with psoriatic arthritis who had poor response to traditional treatments. After receiving the anti-interleukin (IL)-17 monoclonal antibody (ixekizumab), the arthritis symptoms were significantly relieved, while CD4+ T cell count increased and the viral load of HIV-1 remained undetectable in combination with antiretroviral therapy (ART). In conclusion, anti-IL-17 monoclonal antibody is a promising and safe treatment for psoriatic arthritis in HIV-positive patients.

Drug resistance mutation profiles of the drug-naïve and first-line regimen-treated HIV-1-infected population of Suzhou, China.

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance (TDR) and acquired drug resistance mutation (ADR) profiles, we collected blood specimens from 127 drug-naïve and 117 first-line drug-treated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified pol fragments from 100 drug-naïve and 20 drug-treated samples. We then determined the drug-resistant mutations to protease (PR) and reverse-transcriptase (RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted (drug-naïve group) and acquired (treated group) resistance mutations, respectively. Six transmitted drug-resistant mutations were found, including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region. Only L76V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.