Clinical and immunological features of psoriasis vulgaris in HIV-infected patients

Introduction. Psoriasis is an inflammatory dermatosis, which has characteristic clinical features and is closely associated with immunological changes in the skin. HIV-infected patients suffering from psoriasis have immunological features associated with the effect of HIV virus on CD4+T-lymphocytes.Aim. To identify clinical features of psoriasis in HIV-infected patients depending on the stage of HIV infection and immune status.Materials and methods. An open prospective study (2014–2018) included 143 patients with psoriasis vulgaris, of which 79 (55.2%) were infected with HIV and 64 (44.8%) were not infected with HIV. The groups were comparable in terms of age and gender. The diagnosis of psoriasis vulgaris was established with due account for its clinical presentation and histologically confirmed in 29 (20.3%) patients, of which 17 (58.6%) were infected with HIV and 12 (41.4%) were not infected with HIV. In a biopsy, tissue samples were taken from the areas of inflammatory and healthy skin in each patient. Numbers of CD4+ and CD8+T-lymphocytes in the biopsy samples obtained were calculated using immunohistochemical staining of biopsy. The severity of psoriasis progress was assessed using the psoriasis lesions severity index, taking into account the body surface area covered by lesions, the intensity of erythema, infiltration and sloughing of skin. In the course of the study, the patients had general clinical examinations performed, their HIV infection confirmed or denied, their immune status assessed, and their clinical stage of HIV infection determined.Results and discussion. Mild psoriasis was less often identified, and moderately severe and severe psoriasis was more often observed in HIV-infected patients as compared to HIV-negative patients. The psoriatic plaque CD8+T-lymphocyte counts in HIV-infected patients grew with increasing immunosuppression and clinical stage of HIV infection; these changes were not observed in HIV-negative patients.Сonclusion. HIV-infected patients often have moderately severe (39.2%) and severe (22.8%) psoriasis vulgaris. The psoriatic plaque CD8+T-lymphocyte counts in HIV-infected patients predominate over the CD4+T-lymphocyte counts, while the HIV-negative patients show the opposite test results.

Presence of TRPA1 Modifies CD4+/CD8+ T Lymphocyte Ratio and Activation

Transient Receptor Potential Ankyrin 1 (TRPA1) has been reported to influence neuroinflammation and lymphocyte function. We analysed the immune phenotype and activation characteristics of TRPA1-deficient mice (knockout—KO) generated by targeted deletion of the pore-loop domain of the ion channel. We compared TRPA1 mRNA and protein expression in monocyte and lymphocyte subpopulations isolated from primary and secondary lymphatic organs of wild type (WT) and KO mice. qRT-PCR and flow cytometric studies indicated a higher level of TRPA1 in monocytes than in lymphocytes, but both were orders of magnitude lower than in sensory neurons. We found lower CD4+/CD8+ thymocyte ratios, diminished CD4/CD8 rates, and B cell numbers in the KO mice. Early activation marker CD69 was lower in CD4+ T cells of KO, while the level of CD8+/CD25+ cells was higher. In vitro TcR-mediated activation did not result in significant differences in CD69 level between WT and KO splenocytes, but lower cytokine (IL-1β, IL-6, TNF-α, IL-17A, IL-22, and RANTES) secretion was observed in KO splenocytes. Basal intracellular Ca2+ level and TcR-induced Ca2+ signal in T lymphocytes did not differ significantly, but interestingly, imiquimod-induced Ca2+ level in KO thymocytes was higher. Our results support the role of TRPA1 in the regulation of activation, cytokine production, and T and B lymphocytes composition in mice.

Role of Biomarkers in the Stratification of COVID-19 Disease Severity – A Review

Background: There have been a wide variety of clinical publications on coronavirus disease 19 (COVID-19) focused on specific biomarkers. Acute-phase reactants, such as C-reactive protein (CRP), ferritin, serum amyloid A (SAA), and procalcitonin, have been identified as sensitive markers of acute COVID-19 illness, even though they are nonspecific markers. Objective: The purpose of this study is to summarize the role of several biomarkers in the stratification of COVID-19 disease severity. Methods: This study followed systematic literature review method. The systematic review followed the review process as it was well developed and planned to reduce biases and eliminate irrelevant and low-quality studies. The steps for implementing a systematic review include correctly formulating the COVID-19 question to answer, developing a protocol based on inclusion and exclusion criteria, performing a detailed and broad literature search and screening the abstracts of the studies identified in the search and subsequently of the selected complete texts. After selecting the study, the next steps were synthesis of the evidence like extract the necessary data into a form designed in the protocol to summarise the included studies, assess the biases of each study, identifying the quality of the available evidence, and develop tables and text that synthesise the evidence. The secondary sources of data for this study included different published topics from national & international journals. Good number of Journal articles was taken regarding “Role of Biomarkers in the Stratification of COVID-19”. Published articles were collected from renowned indexing data source like PubMed, Medline, and Scopus. Etc. Conclusion: Significantly increased white blood cell count, lymphopenia, decreased CD3, CD4, or CD8 T-lymphocyte counts, high neutrophil count, thrombocytopenia, and dramatically elevated inflammatory biomarkers were all linked to severe disease and the probability of developing sepsis as the disease progressed. Progressive decreases with lymphopenia, thrombocytopenia, elevated CRP, procalcitonin, increased liver enzymes, impaired renal function, and coagulation derangements were more common in critically sick patients and were linked to a higher rate of clinical sequelae. In seriously and critically ill patients, elevated interleukin levels and significantly increased SAA were most frequently reported. The neutrophil to lymphocyte ratio, the systemic immune inflammation index, and the COVID-19 Severity Score are all indicators of systemic inflammation that can be used to predict disease severity, outcome, and death.

Human Immunodeficiency Virus Infection Promotes Human Papillomavirus-Mediated Anal Squamous Carcinogenesis: An Immunologic and Pathobiologic Review

<b><i>Background:</i></b> Anal squamous cell carcinoma (SCC) is a rare gastrointestinal malignancy with rising incidence, both in the United States and internationally. The primary risk factor for anal SCC is human papillomavirus (HPV) infection. However, there is a growing burden of disease in patients with human immunodeficiency virus (HIV) and HPV coinfection, with the incidence of anal SCC significantly increasing in this population. This is particularly true in HIV-infected men. The epidemiologic correlation between HIV-HPV coinfection and anal SCC is established; however, the immunologic mechanisms underlying this relationship are not well understood. <b><i>Summary:</i></b> HIV-related immunosuppression due to low circulating CD4+ T cells is one component of increased risk, but other mechanisms, such as the effect of HIV on CD8+ T lymphocyte tumor infiltration and the PD-1/PD-L1 axis in antitumor and antiviral response, is emerging as significant contributors. The goal of this article is to review existing research on HIV-HPV coinfected anal SCC and precancerous lesions, propose explanations for the detrimental synergy of HIV and HPV on the pathogenesis and immunologic response to HPV-associated cancers, and discuss implications for future treatments and immunotherapies in HIV-positive patients with HPV-mediated anal SCC. <b><i>Key Messages:</i></b> The incidence of anal squamous cell carcinoma is increased in human immunodeficiency virus (HIV)-infected patients, even in patients on highly active antiretroviral therapy. Locoregional HIV infection may enhance human papillomavirus oncogenicity. Chronic inflammation due to HIV infection may contribute to CD8+ T lymphocyte exhaustion by upregulating PD-1 expression, thereby blunting cytotoxic antitumor response.

Programmed Cell Death Protein 1-overexpressed CD8+ T Lymphocytes Play a Role in Increasing Chronic Hepatitis B Disease Progression

BACKGROUND: T lymphocyte activation depends on the balance of co-stimulatory and co-inhibitory signals determined by Cluster of Diffrentiation (CD)28 and Programmed Cell Death Protein 1 (PD-1) expression. Alteration in CD28 and PD-1 expression might affect the progression of chronic hepatitis B (CHB). Current study was conducted to evaluate the correlations of the CD28 and PD-1 expressions of T lymphocytes and CHB progression.METHODS: Subjects were recruited, selected and divided into 3 groups, inactive CHB, active CHB and CHB with End-Stage Liver Disease (ESLD). HBeAg was determined by using Enzyme-Linked Fluorescence Assay while HBV-DNA was carried out by the RT-PCR method. Numbers of T lymphocytes expressing CD3, CD4, CD8, CD45, CD28 and PD-1 molecules were determined by flowcytometry. RESULTS: There was no significant difference in the expression of CD28 by CD4+ and CD8+ T lymphocytes of inactive CHB, active CHB and CHB with ESLD subjects. There was also no significant difference in the expression of PD-1 in CD4+ lymphocytes of inactive CHB, active CHB and ESLD subjects. In contrast there was a significant increase in the expression of PD-1 in CD8+ T lymphocytes of ESLD subjects.CONCLUSION: CD28 expression among CHB subjects was within normal range and not related to disease progression, but PD-1 expression of CD8+ T lymphocyte was increased along with disease progression, especially in CHB subjects with ESLD. This suggests that PD-1-overexpressed CD8+ T lymphocyte play a role in increasing CHB disease progression.KEYWORDS: chronic hepatitis B, CD28, PD-1, T lymphocyte, disease progression

CD8+ T lymphocyte is a main source of interferon-gamma production in Takayasu’s arteritis

Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu’s arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = − 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients.

Clinical Outcome Prediction in COVID-19 Patients by Lymphocyte Subsets Analysis and Monocytes’ iTNF-α Expression

In December 2019, a novel coronavirus, “SARS-CoV-2”, was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

Platelet EVs contain an active proteasome involved in protein processing for antigen presentation via MHC-I molecules

In addition to their hemostatic role, platelets play a significant role in immunity. Once activated, platelets release extracellular vesicles (EVs) formed by budding of their cytoplasmic membranes. Because of their heterogeneity, platelet EVs (PEVs) are thought to perform diverse functions. It is unknown, however, whether the proteasome is transferred from platelets to PEVs or whether its function is retained. We hypothesized that functional protein processing and antigen presentation machinery is transferred to PEVs by activated platelets. Using molecular and functional assays, we show that the active 20S proteasome is enriched in PEVs along with MHC-I and lymphocyte costimulatory molecules (CD40L and OX40L). Proteasome-containing PEVs were identified in healthy donor blood, but did not increase in platelet concentrates that caused adverse transfusion reactions. They were, however, augmented after immune complex injections in mice. The complete biodistribution of murine PEVs following injection into mice revealed that they could principally reach lymphoid organs such as spleen and lymph nodes, in addition to the bone marrow, and to a lesser extent liver and lungs. The PEV proteasome processed exogenous ovalbumin (OVA) and loaded its antigenic peptide onto MHC-I molecules which promoted OVA-specific CD8+ T lymphocyte proliferation. These results suggest that PEVs contribute to adaptive immunity through cross-presentation of antigens and have privileged access to immune cells through the lymphatic system, a tissue location that is inaccessible to platelets.