Altered Immune Status Research Articles

Gestational breast cancer: distinctive molecular and clinico-epidemiological features

Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6–15% of BC cases in women aged 20–44 years. GBC has worse prognosis than non-GBC, but reasons behind are not clear. The GEICAM/2012–03 Study (Molecular Characterization of Gestational Breast Cancer) is a multicenter prospective/retrospective observational registry of patients diagnosed with GBC. From November 2014 to June 2015 seventy patients diagnosed with GBC were included in the study, 30 diagnosed during pregnancy and 40 after delivery. Our current study was aimed to explore differences in epidemiological, clinico-pathological and gene expression features of GBC tumors, from the GEICAM/2012–03 Study, compared to non-GBC tumors from patients of similar age (< 43 years) from six different GEICAM studies, used as non- GBC control population. As per the main objective, the study found multiple differences showing GBC tumors as a different biological entity. GBC showed a more aggressive biology, with higher Ki67 levels, higher incidence of breast and/or ovarian cancer family history, and germline deleterious BRCA1/2 mutations, and are enriched in basal-like intrinsic subtype. GBC patients showed a lower number of tumor infiltrating lymphocytes, while specific genetic signatures highlight differences in GBC´s distinctive transcriptome. Our study shows that GBC is potentially a clinically and molecularly different entity, with specific epidemiological, clinical, and histological features, as well as a distinctive altered immune state and genetic signature. Nevertheless, further studies are needed to better understand the biology of GBC and to identify new targets against which develop new, more effective, targeted therapies.

Event-free survival in neuroblastoma with MYCN amplification and deletion of 1p or 11q may be associated with altered immune status

BackgroundNeuroblastoma exhibits substantial heterogeneity, which is intricately linked to various genetic alterations. We aimed to explore immune status in the peripheral blood and prognosis of patients with neuroblastoma with different genetic characteristics.MethodsWe enrolled 31 patients with neuroblastoma and collected samples to detect three genetic characteristics. Peripheral blood samples were tested for immune cells and cytokines by fluorescent microspheres conjugated with antibodies and flow cytometry. Event-free survival (EFS) was analyzed using the Kaplan‒Meier method.ResultsTwenty-two patients had genetic aberrations, including MYCN amplification in 6 patients, chromosome 1p deletion in 9 patients, and chromosome 11q deletion in 14 patients. Two genetic alterations were present in seven patients. The EFS was worse in patients with MYCN amplification or 1p deletion than in the corresponding group, whereas 11q deletion was a prognostic factor only in patients with unamplified MYCN. Changes in immune status revealed a decrease in the proportion of T cells in blood, and an increase in regulatory T cells and immunosuppression-related cytokines such as interleukin (IL)-10. The EFS of the IL-10 high-level group was lower than that of the low-level group. Patients with concomitant genetic alterations and a high level of IL-10 had worse EFS than other patients.ConclusionsPatients with neuroblastoma characterized by these genetic characteristics often have suppressed T cell response and an overabundance of immunosuppressive cells and cytokines in the peripheral blood. This imbalance is significantly associated with poor EFS. Moreover, if these patients show an elevated levels of immunosuppressive cytokines such as IL-10, the prognosis will be worse.

Endogenous Endophthalmitis Associated With COVID-19: A Systematic Review on Its Incidence, Risk Factors, Causative Organisms, and Prognosis.

Endogenous endophthalmitis (EE) is a rare but severe intraocular infection resulting from hematogenous dissemination of microorganisms. During the COVID-19 pandemic, there has been a notable increase in EE cases. This literature review aims to evaluate studies focusing on EE associated with COVID-19 to elucidate its pathogenesis and optimize patient management strategies. A thorough search was conducted across PubMed, ScienceDirect, and Google Scholar for relevant research.The surge in EE cases during the COVID-19 pandemic is likely linked to alterations in immune status and systemic comorbidities exacerbated by the virus and its treatments. Notably, Candida albicans and Aspergillus species emerged as the predominant fungal pathogens in these cases. The findings suggest that the increased incidence of EE is associated with immune dysregulation and increased vulnerability of COVID-19 patients, particularly those with severe diseases or undergoing immunosuppressive treatments.Early diagnosis with timely and effective treatment is crucial for improving patient outcomes. Regular ophthalmic evaluations for hospitalized COVID-19 patientsare strongly advised to detect and address ocular complications early.

Colitis associated with persistent drug-induced immune dysregulation.

Adverse drug reactions frequently involve the gastrointestinal tract. We present two cases of colitis that occurred months to years after chemotherapy and autologous stem cell transplantation for the treatment of lymphoma. Laboratory tests revealed altered immune status with decreased CD4/CD8 ratio and hypogammaglobinemia (in one patient). The patients had no history of inflammatory bowel disease or immunodeficiency. Biopsies showed chronic active colitis with crypt architectural distortion, erosions, and ulcers as well as pyloric gland metaplasia and loss of plasma cells (in one patient, respectively). Colitis appeared to be related to lymphoma therapy, but could not be attributed to a distinct drug or infectious agent, suggesting the concept of persistent immune dysregulation driving mucosal inflammation. Hence, we suggest "immune dysregulation-associated colitis" (ID-colitis) as an umbrella term for cases of chronic colitis, in which immune dysfunction is evident from blood samples or clinical information and inflammatory bowel disease has been ruled out.

From Womb to World: Exploring the Immunological Connections between Mother and Child.

Mother and child are immunologically interconnected by mechanisms that we are only beginning to understand. During pregnancy, multiple molecular and cellular factors of maternal origin are transferred across the placenta and influence the development and function of the fetal and newborn immune system. Altered maternal immune states arising from pregnancy-associated infections or immunizations have the potential to program offspring immune function in ways that may have long-term health consequences. In this study, we review current literature on the impact of prenatal infection and vaccination on the developing immune system, highlight knowledge gaps, and look to the horizon to envision maternal interventions that could benefit both the mother and her child.

Herpes zoster infection in pregnancy: features and consequences.

Herpes (varicella) zoster (HZ) infection occurs in 4 people per 1000 in the general US population (irrespective of prior varicella infection and vaccination status) each year and has been the subject of scientific inquiry for decades. The consequences of infection are myriad and may depend on the dermatome of involvement as well as host factors such as age, comorbidities, prior treatment or immunization, and immunologic status. Pregnancy is associated with an altered immune and hormonal status in the mother. While maternal HZ infection during pregnancy is not uncommon, the implications for both mother and child are not well established, although multiple studies of perinatal maternal HZ infection suggest no intrauterine transmission to the fetus. We review the current literature on herpes zoster infection in pregnancy, including epidemiology, diagnosis, potential immunologic sequelae, and strategies for prevention and treatment.

Epidermal barrier impairment predisposes for excessive growth of the allergy-associated yeast Malassezia on murine skin.

The skin barrier is vital for protection against environmental threats including insults caused by skin-resident microbes. Dysregulation of this barrier is a hallmark of atopic dermatitis (AD) and ichthyosis, with variable consequences for host immune control of colonizing commensals and opportunistic pathogens. While Malassezia is the most abundant commensal fungus of the skin, little is known about the host control of this fungus in inflammatory skin diseases. In this experimental study, MC903-treated mice were colonized with Malassezia spp. to assess the host-fungal interactions in atopic dermatitis. Additional murine models of AD and ichthyosis, including tape stripping, K5-Nrf2 overexpression and flaky tail mice, were employed to confirm and expand the findings. Skin fungal counts were enumerated. High parameter flow cytometry was used to characterize the antifungal response in the AD-like skin. Structural and functional alterations in the skin barrier were determined by histology and transcriptomics of bulk skin. Finally, differential expression of metabolic genes in Malassezia in atopic and control skin was quantified. Malassezia grows excessively in AD-like skin. Fungal overgrowth could, however, not be explained by the altered immune status of the atopic skin. Instead, we found that by upregulating key metabolic genes in the altered cutaneous niche, Malassezia acquired enhanced fitness to efficiently colonise the impaired skin barrier. This study provides evidence that structural and metabolic changes in the dysfunctional epidermal barrier environment provide increased accessibility and an altered lipid profile, to which the lipid-dependent yeast adapts for enhanced nutrient assimilation. Our findings reveal fundamental insights into the implication of the mycobiota in the pathogenesis of common skin barrier disorders.

Immunomodulatory Effects of Chemo-Immunotherapy ± Idelalisib in Chronic Lymphocytic Leukaemia (CLL)

Introduction: Chronic lymphocytic leukaemia (CLL) is characterised by a dysfunctional immune profile. However, the precise impact of therapy on this altered immune state, both short and long term, remains unclear. The collection of pre-treatment and longitudinal blood samples in the NCRI phase III RIAltO trial (NCT01678430) offered a unique opportunity to address this question in the context of frontline chemo-immunotherapy (CIT) containing bendamustine or chlorambucil. The factorial randomisation to idelalisib versus placebo also provided a framework for investigating the immunomodulatory effects of PI3Kδ inhibition in this setting. Methods: We conducted mass cytometry analysis on samples obtained from CLL patients enrolled in the RIAltO trial. Patients were randomly assigned to receive ofatumumab plus either bendamustine or chlorambucil, with or without idelalisib. Samples were collected before treatment and at early (median 5.9 [IQR 5.7 - 6.4] months) and late (18.5 [16.1 - 22.6] months) post-treatment timepoints. Three healthy controls (HC) were included for comparison. CD3 + T cells were analysed using a customised CyTOF panel comprising 36 markers. Uniform manifold approximation and projection (UMAP) and manual gating analysis were utilised to evaluate global and specific T-cell changes. Results: In all, 177 samples from 79 CLL patients, obtained before or after CIT, were analysed. Baseline characteristics were similar between the different treatment arms. Compared to HC, treatment-naïve CLL patients exhibited a distinct T-cell profile with increased regulatory T cells, decreased naïve and central memory (CM) cells, elevated effector memory (EM) cells, reduced non-senescent cells, and increased expression of HLA-DR, PD-1, TOX, T-bet, and Eomes. Following CIT, the T-cell profile was significantly altered but remained distinct from that of HCs. CIT-induced changes persisted at the late post-treatment timepoint, indicating a sustained effect. Analysis of specific T-cell populations showed that, although some CLL-associated features became less prominent following CIT (expression of PD-1, TOX and TIGIT), most were enhanced (shift from naïve and CM cells towards a terminal effector phenotype; shift from a non-senescent to a terminally senescent phenotype; increased HLA-DR and T-bet expression). The post-treatment immune profiles were similar in patients receiving bendamustine or chlorambucil. Despite its immunomodulatory effects when used as a single agent, idelalisib also induced minimal additional changes. Furthermore, the post-treatment immune profile was similar in patients achieving minimal residual disease (MRD) negativity versus those who remained MRD positive, suggesting a direct pharmacodynamic effect. Finally, non-metric multidimensional scaling (NMDS) analysis demonstrated that CIT shifted the overall CLL-associated immune profile further away from that of HC, and that the shift was independent of chemotherapy allocation, idelalisib, or the level of CLL cytoreduction achieved. Conclusion: CIT results in profound immune changes that persists up to 18.5 [16.1 - 22.6] months following treatment. Furthermore, the overall effect of these changes further differentiates the CLL-associated immune profile from that of HC, deepening the existing T-cell dysfunction irrespective of chemotherapy choice, or the addition of idelalisib. Our study has important potential implications for patients receiving CIT in a range of clinical settings and supports the move towards more targeted agents that are less likely to cause indiscriminate immune perturbation.

HIV-Related Diffuse Large B Cell Lymphoma Influences on T Cell Exhaustion

BACKGROUD HIV infection leads to T cell dysfunction, which triggers increased incidence of diffuse large B cell lymphoma (DLBCL). It has been shown that PD-1 inhibitors can better restore T cell function and effectively treat HIV-related lymphoma. However, the specific mechanism on the treatment of HIV-related DLBCL patients with PD-1 inhibitors is ambiguous, and related studies on the expression of PD-1 on T cells have not been reported. This study aimed to explore the regulatory role of altered immune function status in the microenvironment of HIV-related DLBCL and to analyze hyper-exhausted T cell subsets. METHODS Three patients with DLBCL, two patients with HIV and 11 patients with HIV-related DLBCL who were treated from September 2021 to December 2022 at the Chongqing University Cancer Hospital of were included. Single cell sequencing was used to analyze immune cell and tumor cell related genes in patients'lymph node tissues. InferCNV was used to distinguish normal and malignant B lymphocytes. Gene set enrichment analysis (GSEA) was used to find the expression of exhaustion genes and related signaling pathways in immune cells. And relevant exhausted immune cells were analyzed and validated by flow cytometry. RESULTS Compared to the HIV and DLBCL groups, the HIV-related DLBCL group had a higher level of expression of the gene PDCD1, a higher level of expression of CD23(FCER2) in normal B lymphocytes, and a greater difference in malignant B lymphocytes, with a lower percentage of TCF1-positive exhausted T cells and a higher level of CXCL13-positive exhausted T cells (Fig.1-3). Compared with the HIV group, the percentage of follicular helper T cells (T fh) was lower in the HIV-related DLBCL group. The results of the Pseudotime analysis showed two main developing directions of TCF1-positive exhausted T cells (Fig.4). The state2 was primarily the direction of TCF1-positive exhausted T cell development in the HIV group and the HIV-related DLBCL group, and the state3 was primarily the direction of TCF1-positive exhausted T cell development in the DLBCL group and the HIV-related DLBCL group. CONCLUSION Patients with HIV-related DLBCL are more at risk of T cell exhaustion. In this study, we found that HIV-related DLBCL induced T cell exhaustion has different states and shows two differentiation directions, and state2 may correlate with HIV-induced T cell exhaustion. T cell exhaustion states may be used for disease status and clinical efficacy assessment of HIV-related DLBCL.

Senescence and Mitochondrial Transfer Ability of Bone Marrow Mesenchymal Stromal Cells Influence Patterns of Alloreactivity after Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However post-transplant disease recurrence and alloreactive complications (chiefly graft versus host diseases - GvHD) are still associated with severe morbidity and mortality. Proliferative advantage of transformed cells as well as immune and microenvironmental dysregulations contribute both to promoting relapse and escape from graft versus leukemia (GvL) effect. Bone marrow (BM) mesenchymal stromal cells (MSC) are well known for their role in hematopoiesis and immune modulation. MSCs have been shown able to transfer mitochondria (MT) to different cell populations, including immune effectors, in order to (re)establish a healthy oxidative metabolism within the recipient cell. Here we hypothesize that these mechanisms are highly active in BM microenvironment after allo-HSCT and may contribute to alloreactivity, modifying the immune environment. On this basis we stipulate that those intercellular exchanges are deeply impacted by MSCs' senescence, that could be deployed as a useful parameter to predict post-transplant outcomes. To that end, we conducted a translational research, based on BM specimens prospectively collected at our Institution (NCT03357172, NCT03964922), involving patients undergoing allo-HSCT for high-risk MDS and AML and receiving fludarabine/busulfan-based conditioning regimens, anti-lymphoglobuline and cyclosporin/mycophenolate mofetil. MSC phenotype and functionality at the pre-transplant stage, MT capacity, immunomodulation towards T cells and phenotype were studied by multiparametric flow cytometry. Cell metabolism, in terms of oxygen consumption and extracellular acidification rate, was characterized with Seahorse XF technology. Percentages of senescent MSCs were determined with SA β-galactosidase test. First, we compared phenotypic and metabolic characteristics of MSC from MDS/AML (N=29) patients with those retrieved from a cohort of healthy controls (N=8). We observed that patient MSCs were characterized by higher expression of CD157 and CD146 and lower expression of CD200 as compared to healthy MSCs. Pre-transplant senescence quantification highlighted a certain degree of heterogeneity within the MSC compartment in leukemic patients (median = 37.42% sd=16.30 for AML patient and m=11.74% sd=6.4 for HC). In an attempt to link clinical phenotypes to this heterogeneity, we observed that patients with high degree of MSC senescence in pretransplant samples (mean= 51.6% sd=16.6 cells/sample), developed more frequently acute GvHD, as compared to those with low degree of pre-transplant MSC senescence (mean= 23.8% sd=14.3) who experienced instead a higher incidence of disease relapse (p=0,004). Assuming that the link between senescence and alloreactivity could rely to different metabolic states and MT capabilities in MSCs, we analyzed these biological features in our samples. Indeed, we observed that low degree of MSC senescence was associated with higher MT to T cells, in particular to CD4+ cells, shifting their metabolism and phenotype toward an immunosuppressive state The characterization of cellular metabolism showed in highly senescent MSCs the presence of markers of mitochondrial dysfunction with high oxidative power, but reduced coupling efficiency of respiratory chain. This metabolic profile involved a high mitochondrial mass characterized by a high maximal respiration capacity compared to HC MSCs. The in vitro modulation of MSC senescence with nicotinamide administration restored healthy mitochondrial metabolism and improved coupling efficacy of oxidative phosphorylation, possibly impacting on the immunomodulation capabilities of this microenvironment component. Here for the first time, we provide the evidence that MSC senescence plays an pivotal role in defining an altered immune state in transplanted AML possibly shifting the degree of alloreactivity from a high GvH/GvL response (high GvHD and low relapse) to a high immunosuppressive state (low GvHD and high relapse). These findings pave the way for implementing MSC senescence as a biomarker able to predict post-transplant outcomes and show new biological rationales to integrate donor-derived MSC products to better adjust GvH responses.

Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study

Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of psychedelics on immune functioning, HPA axis activity in response to stress, and associated psychological outcomes is preliminary. To address this, we conducted a placebo-controlled, parallel group design comprising of 60 healthy participants who received either placebo (n = 30) or 0.17 mg/kg psilocybin (n = 30). Blood samples were taken to assess acute and persisting (7 day) changes in immune status. Seven days’ post-administration, participants in each treatment group were further subdivided: 15 underwent a stress induction protocol, and 15 underwent a control protocol. Ultra-high field (7-Tesla) magnetic resonance spectroscopy was used to assess whether acute changes in glutamate or glial activity were associated with changes in immune functioning. Finally, questionnaires assessed persisting self-report changes in mood and social behavior. Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin (IL)- 1β, IL-6, and C-reactive protein (CRP)) remained unchanged. Seven days later, TNF-α concentrations returned to baseline, while IL-6 and CRP concentrations were persistently reduced in the psilocybin group. Changes in the immune profile were related to acute neurometabolic activity as acute reductions in TNF-α were linked to lower concentrations of glutamate in the hippocampus. Additionally, the more of a reduction in IL-6 and CRP seven days after psilocybin, the more persisting positive mood and social effects participants reported. Regarding the stress response, after a psychosocial stressor, psilocybin did not significantly alter the stress response. Results are discussed in regards to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.

Age-related cytokine imbalance in the thymus in sudden infant death syndrome (SIDS)

BackgroundSudden infant death syndrome (SIDS) has been considered to be triggered by a combination of underlying immune dysregulation and infections. The thymus is a crucial lymphatic organ responsible for T cell development in infancy. We hypothesized that an altered thymic immune status may be detectable by intrathymic cytokine profiling in SIDS.Methods27 cytokines in protein lysates of thymus tissue and thymus weights were assessed in 26 SIDS cases and 16 infants who died of other reasons.ResultsSeventeen out of 27 cytokines were increased in thymic tissue of SIDS compared to controls without infections, and the most significant discrepancy was in infants younger than 20 weeks. The thymic cytokine profiles in SIDS cases were similar to those in controls with severe infection; however, the magnitude of the cytokine concentration elevation in SIDS was less pronounced, indicating sub-clinical infections in SIDS. In contrast to SIDS, intrathymic cytokine concentrations and thymus weight were increased with age in control children.ConclusionsElevated thymic cytokine expression and thymus weight, as well as impaired age-related alterations in SIDS, may be influenced by subclinical infection, which may play a role in initiating SIDS in infants with a compromised immune response.Impact StatementIncreased thymic weight and cytokine concentration may suggest possible subclinical infection in SIDS.Elevated thymic weight and cytokine concentration mainly in SIDS cases aged <20 weeks.Age-related impairment in the thymic weight and cytokine expression may be impaired by subclinical infection in SIDS.

Maternal COVID-19 during pregnancy results in altered immune status at birth and increases the risk for early life infections

Maternal COVID-19 during pregnancy results in altered immune status at birth and increases the risk for early life infections

Prevalence and impact of antithyroid antibodies in children with immune thrombocytopenic purpura

Abstract Background Immune thrombocytopenia (ITP) is a common autoimmune condition characterized by isolated thrombocytopenia. ITP can present either as a primary disorder or secondary to other diseases, such as infections or altered immune states. The aim of this work was to evaluate the prevalence of antithyroid autoantibodies found at the time of diagnosis of childhood ITP and their influence on treatment response, in addition to prevalence of antiplatelet antibodies and thyroid dysfunction in pediatric patients with ITP. Patients and methods This prospective controlled study was carried out on 50 children with newly diagnosed primary ITP, and 50 apparently healthy children served as a control group. Serum levels of thyroid-stimulating hormone, free thyroxin and free triiodothyronine), anti-thyroglobin, anti-peroxidase antibodies, and antiplatelet antibodies were evaluated at diagnosis. Results Anti-thyroglobin, anti-peroxidase antibodies, and antiplatelet were significantly positive in children with ITP than the control group. Patients with positive antiplatelet, anti-thyroglobin, and anti-peroxidase antibodies show more resistance to effective medications in comparison to ITP patients with negative antibodies (P&lt;0.001). The relation of these antibody positivity and the clinical course of these groups was statistically significant. Conclusions Pediatric ITP patients are prone to develop autoantibodies such as antiplatelet antibodies. Also, anti-thyroglobin and anti-peroxidase antibodies were significantly higher in children with ITP with positive antiplatelet, and both show more resistance to effective medications with relatively good response to eltrombopag olamine in comparison to ITP patients with negative antiplatelet, anti-thyroglobin, and anti-peroxidase antibodies.

Studies on modulation of hemocyte surface antigen through agglutination reaction under arsenic toxicity in edible mudcrab (Scylla serrata)

Scylla serrata (Crustacea: Decapoda), which is widely spread on the intertidal mudflat of West Bengal, India's Sundarbans Biosphere Reserves, is a potential aqua crop and an economically significant edible species. One of the larger crab groups in the mangrove swamp of the Sundarbans is thought to be this one. The S. serrata's multifaceted immune response is directly tied to its diverse habitat and survival technique. It lives in dangerous surroundings and is constantly in danger of physiological stress brought on by various xenobiotics, such as arsenic. By producing a number of polyclonal antisera in rabbits (New Zealand White, albino), the study attempted to evaluate the surface antigen against crab hemocytes and murine lymphocytes. Control hemocytes and hemocytes treated to 1 ppm expressed very identical reactivity to antihemocyte sera for the agglutination reaction. The control results, however, shifted when exposed to 2 and 3 ppm of sodium arsenite, indicating arsenic-induced hemocyte surface modification. The agglutination reaction from the control sets of hemocytes that reacted with murine anti-lymphocyte sera gradually, shifted as the quantity of sodium arsenite in the medium of the treatment sets increased. The maximum equivalence zone of murine lymphocyte and hemocyte agglutination 98.6% and 99% respectively suggested a potential epitope sharing between two phylogenetically separate species. The situation may lead to a possible alteration of immune status and make opportunity for pathogenic foreign invaders within the mud crab body. Chronic arsenic exposure indicated a steady decline of edible and demandable S. serrata in the natural habitat of Sundarbans.

Presumed viral endotheliitis following topical mitomycin C for the treatment of ocular surface squamous neoplasia in a glaucoma patient

Corneal endotheliitis and ocular surface neoplasia are known to be associated with altered immune status especially in the elderly. We reviewed an interesting case where endotheliitis occurred for the first time while on topical chemotherapy for ocular surface neoplasia in a patient with glaucoma. We have addressed the practical concerns in decision-making given multiple ocular comorbidities and highlighted a successful outcome with no recurrence of both the tumor and the endotheliitis for over 16 months.

Lactobacillus coryniformis subsp. torquens inhibits bone loss in obese mice via modification of the gut microbiota.

High-fat diet (HFD)-induced obesity results in bone loss associated with an imbalanced gut microbiota and altered immune status. Probiotics are live microorganisms that are beneficial to the host and are important in maintaining bone health and gut homeostasis. In this study, the probiotic Lactobacillus coryniformis subsp. torquens (T3L) was isolated from traditional yak milk cheese produced in Lhasa and showed distinct acid and bile salt resistance as potential probiotics. Our data indicated that T3L not only reversed HFD-induced gut dysbiosis, as indicated by decreased Firmicutes-to-Bacteroidetes ratios but also reduced bone loss. The anti-obesity, microbiome-modulating, and bone-protective effects were transmissible via horizontal faeces transfer from T3L-treated mice to HFD-fed mice. The protective effects of T3L on bone mass were associated with regulatory T (Treg) cell-mediated inhibition of osteoclast differentiation. Our data indicate that T3L is a regulator of the gut microbiota and bone homeostasis in an animal model.

Combination of Neuromyelitis Optica Spectrum Disorder with Myasthenia Gravis, Systemic Lupus Erythematosus and Hashimoto's Thyroiditis: A Case of Multiple Autoimmune Syndrome

Autoimmunity reflects an altered immune status. The coexistence of three or more autoimmune diseases in a patient constitutes multiple autoimmune syndrome. Here, an interesting case with a history of Hashimoto's thyroiditis and got the diagnosis of systemic lupus erythematosus during her evaluation, in which the clinical signs of neuromyelitis optica spectrum disorder (NMOSD) and miyasthenia gravis cooccurred will be discussed. In addition to high-dose pulse steroid, plasmapheresis and intravenous immunoglobulin treatments, rituximab treatment was started and the patient is followed up without clinical worsening and disability in the three-year follow-up. Patients with diagnosis of NMOSD need special attention as multiple immune-mediated disorders may be present simultaneously or sequentially during the course of the disease process. This case report emphasizes the importance of a multidisciplinary team approach for a better understanding of disorders related to the breakdown of immune tolerance.

Alteration of immune status during treatment with β-blockers in patients with essential hypertension

The balance of cytokines (IL-2, IL-10, IF-γ) in patients with essential hypertension beforeandaftertreatmentwithβ-blockerswasstudied.20patientsaged45-65yearsbefore and after treatment with β-blockers was studied. 20 patients aged 45-65 years anddiagnosedwithessentialhypertension(12women,8men)wereinvestigated.Forand diagnosed with essential hypertension (12 women, 8 men) were investigated. For thetreatmentofhypertension,patientsreceivedsecond-generationbeta-selectivethe treatment of hypertension, patients received second-generation beta-selective β-blockersEgilokandBetalokZok,andthird-generationβ-blockerNebiletforoneβ-blockers Egilok and Betalok Zok, and third-generation β-blocker Nebilet for one month.Patientsperformedtheirbloodpressuremeasurementsdailyinthemorningmonth. Patients performed their blood pressure measurements daily in the morning duringImonth.Thecontentofinterleukins(IL-2,IL-10,IF-γ)inthebloodbytheduring I month. The content of interleukins (IL-2, IL-10, IF-γ) in the blood by the immuneenzymaticELISAmethodonasemi-automaticreaderStatFax3200withimmune enzymatic ELISA method on a semi-automatic reader Stat Fax 3200 with RayBio,(USA)reagentwasmeasured.TheresultsofourstudiesshowanincreaseRayBio, (USA) reagent was measured. The results of our studies show an increase inthelevelofCD4+(IL-2)cytokinesinthebloodofthestudiedhypertensivein the level of CD4+ (IL-2) cytokines in the blood of the studied hypertensive patients,whichcoincideswiththeliteraturedataontheimportantroleofCD4+patients, which coincides with the literature data on the important role of CD4+ pro-inflammatorycytokinesinthepathogenesisofhypertension.After1monthofpro-infl ammatory cytokines in the pathogenesis of hypertension. After 1 month of treatmentwithβ-blockers,thepatient’sarterialpressureandIL-2levelcontentintreatment with β-blockers, the patient’s arterial pressure and IL-2 level content in theblooddecreased.Thesedataindicatetheimportantroleofinflammationinthethe blood decreased. These data indicate the important role of infl ammation in the pathogenesisofhypertensionandtheanti-inflammatoryeffectsofβ-brokers,usedpathogenesis of hypertension and the anti-infl ammatory effects of β-brokers, used inthetreatmentofhypertension.in the treatment of hypertension

Age- and Sex-Matched Normal Leukocyte Subset Ranges in the General Population Defined with the EuroFlow Lymphocyte Screening Tube (LST) for Monoclonal B-Cell Lymphocytosis (MBL) vs. Non-MBL Subjects.

Reference ranges of blood-circulating leukocyte populations by, e.g., age and sex, are required for monitoring immune-cell kinetics. Most previous reports in which flow cytometry has been used to define the reference ranges for leukocyte counts included a limited number of donors and/or cell populations and/or did not consider age and sex simultaneously. Moreover, other factors not previously considered in the definition of normal ranges, such as the presence of chronic-lymphocytic-leukemia (CLL)-like low-count monoclonal B-cell lymphocytosis (MBLlo), might also be associated with an altered distribution of leukocytes in blood in association with an immunodeficiency and increased risk of infection and cancer. Here, we established reference cell-count ranges for the major populations of leukocytes in blood of non-MBL and MBLlo adult Caucasians matched by age and sex using the EuroFlow Lymphocyte Screening Tube (LST). A total of 706 Caucasian adult donors—622 non-MBL and 84 MBLlo—were recruited from the general population. Among non-MBL donors, the total leukocyte, neutrophil, basophil dendritic cell and monocyte counts remained stable through adulthood, while the absolute numbers of T- and B-cell populations and plasma cells decreased with age. The number of eosinophils and NK-cell increased over time, with clear differences according to sex for certain age ranges. In MBLlo subjects, few differences in the absolute cell counts by age (vs. non-MBL) were observed, and MBLlo men and women showed similar trends to non-MBL subjects except for the B-cell count drop observed in >70 y-men, which was more pronounced in MBLlo vs. non-MBL controls. Building robust age- and sex-matched reference ranges for the most relevant immune-cell populations in the blood of non-MBL donors is essential to appropriately identify an altered immune status in different clinical settings and highlight the altered immune-cell profiles of MBLlo subjects.