Diagnostic challenges and updated therapeutic strategies of Kimura's disease: A case report successfully treated by dupilumab and review.

RATIONALE: Kimura's disease (KD) is a rare and chronic eosinophilic related-disease, characterized by subcutaneous tissue masses, regional enlarged lymph nodes, hypereosinophilia and elevated serum IgE. KD usually affects young adults in the Asian population. In Western countries, the clinical and biological presentation of KD is often unknown, delaying the diagnosis. Therapeutic management is not standardized and despite recent advances, remission from KD can be difficult to achieve, especially in relapse situations. PATIENT CONCERNS: We report the case of an non-Asian man with KD, initially misdiagnosed as lymphoma. We focus on his long-lasting clinical course with 20 years of recurrence despite several therapeutic lines. DIAGNOSES AND INTERVENTIONS: We have emphasized the key points of the KD diagnostic challenge. We chose to focus on hemopathies as diagnostic traps to illustrate several overlapping features that blur frontiers with KD. With regard to treatments, lessons can be learned from the use of the therapeutic backbone, which relies on excision surgery, radiotherapy and corticosteroids. OUTCOMES: Advancements in KD pathogenesis have highlighted the pivotal role of Th2 lymphocytes driving eosinophil activation. Directly inspired by eosinophilic and allergic field practices, targeted therapies, such as dupilumab, provide hope for potential curative options. LESSONS: Finally, we propose a therapeutic plan to treat newly diagnosed KD and discuss options for relapsing entities.

Evidence for a different susceptibility of primate lentiviruses to type I interferons.

Type I interferons induce a complex transcriptional program that leads to a generalized antiviral response against a large panel of viruses, including human immunodeficiency virus type 1 (HIV-1). However, despite the fact that interferons negatively regulate HIV-1 ex vivo, a chronic interferon state is linked to the progression of AIDS and to robust viral replication, rather than protection, in vivo. To explain this apparent contradiction, we hypothesized that HIV-1 may have evolved a partial resistance to interferon, and to test this hypothesis, we analyzed the effects of alpha interferon (IFN-α) on the infectivity of HIV-1, human immunodeficiency virus type 2 (HIV-2), and rhesus monkey simian immunodeficiency virus (SIVmac). The results we obtained indicate that HIV-1 is more resistant to an IFN-α-induced response than are HIV-2 and SIVmac. Our data indicate that the accumulation of viral DNA is more compromised following the infection of IFN-α-treated cells with HIV-2 and SIVmac than with HIV-1. This defect correlates with a faster destabilization of HIV-2 viral nucleoprotein complexes (VNCs), suggesting a link between VNC destabilization and impaired viral DNA (vDNA) accumulation. The differential susceptibilities to IFN-α of the primate lentiviruses tested here do not map to the capsid protein (CA), excluding de facto a role for human tripartite motif protein isoform 5 alpha (Trim5α) in this restriction; this also suggests that an additional restriction mechanism differentially affects primate lentivirus infection. The different behaviors of HIV-1 and HIV-2 with respect to IFN-α responses may account at least in part for the differences in pathogenesis observed between these two virus types.

Functional analysis of the relationship between Vpx and the restriction factor SAMHD1.

SAMHD1 is a newly identified restriction factor that targets lentiviruses in myeloid cells and is countered by the SIV(SM)/HIV-2 Vpx protein. By analyzing a large panel of Vpx mutants, we identify several residues throughout the 3-helix bundle predicted for Vpx that impair both its functionality and its ability to degrade SAMHD1. We determine that SAMHD1 is a strictly non-shuttling nuclear protein and that as expected WT Vpx localizes with it in the nucleus. However, we also identify a functional Vpx mutant with predominant cytoplasmic distribution that colocalizes with SAMHD1 in this location, suggesting that Vpx may also retain SAMHD1 in the cell cytoplasm, prior to its entry into the nucleus. Several mutations in Vpx were shown to affect the stability of Vpx, as well as Vpx:Vpx interactions. However, no strict correlation was observed between these parameters and the functionality of Vpx, implying that neither properties is absolutely required for this function and indicating that even unstable Vpx mutants may be very efficient in inducing SAMHD1 degradation. Overall, our analysis identifies several Vpx residues required for SAMHD1 degradation and points to a very efficient and plastic mechanism through which Vpx depletes this restriction factor.