Circulating Immune Landscape Profiling in Psoriasis Vulgaris and Psoriatic Arthritis by Mass Cytometry.

Background: Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. Methods: We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Results: Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4+ T cells, CD16- NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (TN) and central memory CD4+ T cells (TCM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28hi CD127hi CD4+ TCM cells, CD28hi CD127hi CD4+ TN cells, and CD16- NK cells. Conclusion: In the circulation of PsA patients, the TN and CD4+ TCM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.

Psoriasis and Leprosy: An Arcane Relationship.

Purpose: Psoriasis (Ps) and leprosy are chronic inflammatory skin disorders, characterised by enhanced innate and adaptive immunity. Ps and leprosy rarely coexist. The molecular immune mechanism of the Ps and leprosy rarely coexistence is unclear. Patients and Methods: RNA-sequencing (RNA-seq) was performed on 20 patients with Ps, 5 adults with lepromatous leprosy (L-lep), and 5 patients with tuberculoid leprosy (T-lep) to analyse the differentially expressed genes (DEGs) between them. Moreover, the biological mechanism of Ps and leprosy was explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, Gene Set Enrichment Analysis analysis, and protein-protein interaction (PPI) analyses. Finally, 13 DEGs of 10 skin biopsies of Ps patients, 6 samples of L-lep patients, 6 samples of T-lep patients and 5 healthy controls were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The PPI network was constructed and primarily associated with immune response, IL-17 signalling, and Toll-like receptor pathway between Ps and leprosy. Th17 markers (interleukin (IL)-19, IL-20, IL-36A, IL-36G, IL-22, IL-17A, and lipocalin-2 (LCN2) had higher expression in Ps than in L-lep and T-lep, whereas macrophage biomarkers (CLEC4E and TREM2), SPP1, and dendritic cell (DC)-related hallmarks (ITGAX) and TNF-a had significantly lower expression across Ps and T-lep than in L-lep. Conclusion: To put it simply, Ps patients with IL-17A, IL-19, IL-20, IL-36A, IL-36G, and IL-22 in conjunction with LCN2 with up-graduated expression might be not susceptible to L-lep. However, high levels of CLEC4E, TREM2, and SPP1 in L-lep patients indicated that they unlikely suffered from Ps.

Distinct host immune responses in recurrent vulvovaginal candidiasis and vulvovaginal candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) and vulvovaginal candidiasis (RVVC) are one of the most common gynecological infections, primarily caused by Candida species. Although risk factors of RVVC and VVC have been identified in many studies, antifungal immunological mechanisms are still not fully understood. We performed a 1-year prospective study in a local hospital to monitor 98 patients clinically diagnosed with gynecological Candida infection. The results showed that 20.41% (20/98) are with RVVC, and 79.59% (78/98) patients have VVC. C. albicans accounts for 90% and 96.1% of all strains isolated collected from RVVC and VVC patients, respectively. Antifungal susceptibility testing showed no significant difference in Candida species between RVVC and VVC patients. However, the serum levels of IFN-γ, TNF-α, and IL-17F in the RVVC group were significantly lower than those of the VVC group, while IL-4, IL-6, and IL-10 were higher in the RVVC patients than VVC patients. IL-17A and IL-2 levels were comparable between the two groups. Taken together, our results suggest that the host-immune responses, especially Th1/2 immunity, may play important roles in prognosis of RVVC and VVC.

Progress of the Art of Macrophage Polarization and Different Subtypes in Mycobacterial Infection.

Mycobacteriosis, mostly resulting from Mycobacterium tuberculosis (MTb), nontuberculous mycobacteria (NTM), and Mycobacterium leprae (M. leprae), is the long-standing granulomatous disease that ravages several organs including skin, lung, and peripheral nerves, and it has a spectrum of clinical-pathologic features based on the interaction of bacilli and host immune response. Histiocytes in infectious granulomas mainly consist of infected and uninfected macrophages (Mφs), multinucleated giant cells (MGCs), epithelioid cells (ECs), and foam cells (FCs), which are commonly discovered in lesions in patients with mycobacteriosis. Granuloma Mφ polarization or reprogramming is the crucial appearance of the host immune response to pathogen aggression, which gets a command of endocellular microbe persistence. Herein, we recapitulate the current gaps and challenges during Mφ polarization and the different subpopulations of mycobacteriosis.

Isolation of Novel Mycobacterium Species from Skin Infection in an Immunocompromised Person.

We investigated a case of cutaneous infection in an immunocompromised patient in China that was caused by a novel species within the Mycobacterium gordonae complex. Results of whole-genome sequencing indicated that some strains considered to be M. gordonae complex are actually polyphyletic and should be designated as closely related species.

Transcriptome Analysis Reveals the Molecular Immunological Characteristics of Lesions in Patients with Halo Nevi When Compared to Stable Vitiligo, Normal Nevocytic Nevi and Cutaneous Melanoma.

BACKGROUND: Given their similar appearance and histology, halo nevi (HN) were considered as a type of vitiligo. However, whether HN have stronger immune response than stable vitiligo (VL) remains unclear. In addition, the molecular alterations in HN compared with normal nevocytic nevi (NN) and primary cutaneous melanoma (MM) must be determined. This study aimed to systematically characterize the molecular immunological features of HN. METHODS: Skin samples from patients with HN, VL, NN, and MM were obtained with informed consent. Each of the four groups underwent transcriptome sequencing and data analysis were for pairwise comparison. Quantitative real-time PCR (RT-qPCR) was conducted to confirm the transcriptional expression of some differentially expressed genes (DEGs) that were closely related to immunity. RESULTS: A total of 441 and 1507 DEGs were found in the HN/NN and HN/MM groups, respectively. Compared with those of VL, HN lesions contained 162 up-regulated DEGs and 12 down-regulated DEGs. Bioinformatics analysis showed that the up-regulated genes in HN were substantially enriched in immune response, immune deficiency, and immune rejection; biological stimulation (virus, bacteria); and proliferation and activation of immune cells. Immune cell composition analysis also confirmed high expression levels of multiple immunocytes in HN. CONCLUSION: The molecular immune mechanisms of HN and VL were similar, but the immune activity of HN was stronger than that of VL. Innate and adaptive immunity were involved in the pathogenesis and progression of HN and VL.

Single-Nucleotide Polymorphisms Related to Leprosy Risk and Clinical Phenotypes Among Chinese Population.

BACKGROUND: Genome-wide association studies (GWASs) have identified some immune-related single-nucleotide polymorphisms (SNPs) to be associated with leprosy. METHODS: This study investigated the association of 17 SNPs based on previously published GWAS studies with susceptibility to leprosy, different polar forms and immune states of leprosy in a case-control study from southwestern China, including 1344 leprosy patients and 2732 household contacts (HHCs) (1908 relatives and 824 genetically unrelated contact individuals). The differences of allele distributions were analyzed using chi-squared analysis and logistic regression. RESULTS: After adjusting covariate factors, rs780668 and rs3764147 polymorphisms influenced susceptibilities to genetically related or unrelated leprosy contact individuals. rs142179458 was associated with onset early cases, rs73058713 A allele and rs3764147 A allele increased the risk of reversal reaction, while rs3764147 G allele had higher risk to present lepromatous leprosy and erythema nodosum leprosum. CONCLUSION: Our results demonstrated that genetic variants in the LACC1, HIF1A, SLC29A3 and CDH18 genes were positively correlated with the occurrence of leprosy and leprosy clinical phenotypes, providing new insights into the immunogenetics of the disease.

Malignant syphilis accompanied with neurosyphilis in a malnourished patient: A case report.

BACKGROUND: Syphilis is a common sexually transmitted disease caused by the Treponema pallidum (T. pallidum). Malignant syphilis is a rare presentation of secondary syphilis. Here, we present a case diagnosed with malignant syphilis accompanied with neurosyphilis. CASE SUMMARY: A 56-year-old man present with a 2-mo history of spreading ulcerous and necrotic papules and nodules covered with thick crusts over the face, trunk, extremities, and genitalia. The patient was diagnosed with malignant syphilis accompanied by neurosyphilis based on the characteristic morphology of the lesions, positive serological and cerebrospinal fluid tests for syphilis, brain magnetic resonance imaging, and histopathology, along with resolution of the lesions following the institution of penicillin therapy. The lesions and neurological condition successfully resolved after a course of treatment with penicillin. CONCLUSION: We suggest that neurosyphilis should be considered whenever people have psychiatric symptoms without cutaneous lesions or human immunodeficiency virus.

Different toenail onychomycosis due to Rhodotorula mucilaginosa and Candida parapsilosis in an immunocompetent young adult.

Candida parapsilosis (C. parapsilosis) and Rhodotorula mucilaginosa (R. mucilaginosa) have emerged as a potential pathogen in immunosuppressed hosts; they rarely induce onychomycosis in immunocompetent hosts without assistance from other pathogens. Here we present onychomycosis induced by two strains on different toenails in an immunocompetent young adult. The patient presented with onychomycosis on left and right first toenails due to R. mucilaginosa and C. parapsilosis, respectively. Based on the diagnosis, he had been orally treated with itraconazole 200 twice daily for one week every four weeks that repeated 7 times; however, the toenails did not respond satisfactorily to the treatment. After two months of drug cessation, we confirmed that the two toenails were infected with different fungi. R. mucilaginosa was isolated from the left first toenail, and C. parapsilosis was isolated from the right first toenail. Identifications were confirmed by morphological and cultural characteristics as well as by DNA molecular analysis. After determining in vitro drug susceptibility, the patient was successfully treated with a topical application of ketoconazole cream on the left toenail and oral itraconazole. It is the rare known case of different nails being infected by R. mucilaginosa and C. parapsilosis respectively.

Onychomycosis with greenish-black discolorations and recurrent onycholysis caused by Candida parapsilosis.

Candida parapsilosis (C. parapsilosis) has become a common pathogen, especially in immunocompromised hosts. Here, we present an immunocompetent adult with greenish-black discoloration of the right first finger nail in combination with recurrent onycholysis. C. parapsilosis was isolated from the right first finger nail and was confirmed by morphological characteristics as well as by DNA molecular analysis. Patient was successfully treated with oral itraconazole in a regimen of 5 cycles of 200 mg twice daily for one week, followed by an interruption of treatment for 3 weeks. To our knowledge, this is the first report of C. parapsilosis-induced onychomycosis with recurrent onycholysis.