Young-Hun Cho

Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease

Behçets disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behçets disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçets disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 × 10−8). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 × 10−18, odds ratio = 1.45, 95% CI 1.34–1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 × 10−9, OR = 1.28, 95% CI 1.18–1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production.

Soluble CD93 Induces Differentiation of Monocytes and Enhances TLR Responses

The cell surface protein CD93 is known to be involved in the regulation of phagocytosis and cell adhesion. Although typically membrane-bound, a soluble form of CD93 (sCD93) has recently been identified. Currently, however, the role of sCD93 in monocyte function is unknown. In the current study, we analyzed the functional effects of sCD93 on THP-1 monocytic cells and human primary monocytes. Various forms of recombinant human sCD93 were used to investigate the effects of this molecule on both human primary monocytes and a monocytic cell line, THP-1. We found that sCD93 induced differentiation of monocytes to macrophage-like cells, as evidenced by activated cell adhesion and increased phagocytic activities. In addition, this differentiation resulted in an enhanced response to TLR stimulation in terms of differentiation marker expression and proinflammatory cytokine production. Furthermore, sCD93 enhanced LPS-stimulated TNF-α production even prior to monocyte differentiation. To investigate a possible role for sCD93 in the pathogenesis of chronic inflammatory diseases, we assessed the concentration of sCD93 in synovial fluid from patients with rheumatoid arthritis and found it to be significantly increased compared with synovial fluid from patients with osteoarthritis. Together, these data revealed a function for sCD93 that may have implications in inflammation and inflammatory diseases including rheumatoid arthritis.

Transition from Pemphigus Foliaceus to Pemphigus Vulgaris: Case Report with Literature Review

The transition between the main subtypes of pemphigus, pemphigus vulgaris (PV), and pemphigus foliaceus (PF) has rarely been reported. Moreover, the development of PV in a patient with PF is much more unusual than that of PF in a patient with PV. We report a 48-year-old man who presented with cutaneous lesions showing the typical clinical and histological features of PF. Five years later, his skin lesions became extensive and he developed oral erosions. His condition did not respond well to steroids and azathioprine. Histological examination of a vesicle disclosed suprabasal acantholysis in contrast to the subcorneal acantholysis discovered upon initial histological evaluation. Indirect immunofluorescence revealed IgG antikeratinocyte cell surface antibodies at a titer of 1:640. The titer was 1:160 at initial diagnosis. Upon immunoblotting, the patients serum reacted with 130 kiloDalton (kDa) and 160 kDa proteins, suggesting desmoglein (Dsg) 3 and 1, respectively. We herein report an unusual case of PV that developed from PF during the diseases flare-up.

TNF-α suppresses dendritic cell death and the production of reactive oxygen intermediates induced by plasma withdrawal

Abstract:  Mature dendritic cells (DCs) were generated by culturing human peripheral blood monocytes for 7 days and, then, treating them with a cytokine cocktail for 2 days. The viability of the mature DCs (Day 9) obtained was approximately 60–70%, and this gradually declined when they were recultured in X‐VIVO 15 media containing 2% human plasma (40% viability after 3 days of reculture). DC death accelerated on withdrawing plasma from the culture (20% viability after 3 days). However, the addition of tumor necrosis factor‐α (TNF‐α) to the medium completely restored DC viability in the absence of plasma. Such a protective effect was not afforded by other cytokines, such as granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interleukin‐1α (IL‐1α), IL‐4, IL‐6 and prostaglandin E2 which are used for the maturation of DCs. These results indicate that TNF‐α is specifically required to maintain the viability of mature DCs. The withdrawal of plasma rapidly (within 15 min) elevated cellular levels of reactive oxygen intermediates (ROIs), which have been proposed to regulate the ability of DCs to control inflammatory reactions. The possibility that ROIs act as mediators of DC death was eliminated by the observation that scavengers of ROIs, such as catalase, N‐acetylcysteine, glutathione, failed to prolong DC life span in the absence of plasma. Interestingly, TNF‐α was found to almost completely abolish the production of ROIs induced by plasma withdrawal. To summarize, our results suggest that TNF‐α controls not only the inflammatory functions of DCs but also their survival.