-
BMC Pulmonary Medicine Apr 2020Risk factors affecting the prognosis of acute respiratory distress syndrome (ARDS) in adults were investigated. The aim was to identify new predictors for ARDS patient... (Observational Study)
Observational Study
BACKGROUND
Risk factors affecting the prognosis of acute respiratory distress syndrome (ARDS) in adults were investigated. The aim was to identify new predictors for ARDS patient prognosis, including those with clinical, pathophysiological, and atypical immunodeficiency.
METHODS
ARDS patients were retrospectively included. The patients were grouped and analysed according to different oxygenation index grades and prognosis, and factors influencing prognosis and survival were examined. Adolescent patients, patients with typical immunodeficiency and patients who died within 24 h after being diagnosed with ARDS were excluded. The predictive value for mortality was determined by Cox proportional hazard analysis.
RESULTS
In total, 201 patients who fulfilled the Berlin definition of ARDS were included. The severity of critical illness on the day of enrolment, as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.016), Sequential Organ Failure Assessment (SOFA) score (P = 0.027), and PaO/FiO (P = 0.000), worsened from mild to severe ARDS cases. Compared with survivors, non-survivors were significantly older and had higher APACHE II and SOFA scores. Moreover, significantly lower lymphocyte/neutrophil ratios and leukocyte counts were found among non-survivors than survivors (P = 0.008, P = 0.012). A moderate positive correlation between the lymphocyte/neutrophil and PaO/FiO ratios (P = 0.023) was observed. In predicting 100-day survival in patients with ARDS, the area under the curve (AUC) for the lymphocyte/neutrophil ratio was significantly higher than those for the PaO/FiO ratio alone, body mass index (BMI) alone, and the lymphocyte count alone (P = 0.0062, 0.0001, and 0.0154). Age (per log years), BMI < 24, SOFA score, leukocyte count, and the lymphocyte/neutrophil ratio were independent predictors of 28-day mortality in ARDS patients. Additionally, ARDS patients with a lymphocyte/neutrophil ratio < 0.0537 had increased 28-day mortality rates (P = 0.0283). Old age affected both 28-day and 100-day mortality rates (P = 0.0064,0.0057).
CONCLUSIONS
Age (per log years), BMI < 24, SOFA score, lymphocytes, and the lymphocyte/neutrophil ratio were independent predictors of 100-day mortality in patients with ARDS. The lymphocyte/neutrophil ratio may represent a potential molecular marker to evaluate atypical immunosuppression or impairment in patients with ARDS.
Topics: APACHE; Adult; Aged; Body Mass Index; Female; Humans; Intensive Care Units; Lymphocytes; Male; Middle Aged; Neutrophils; Predictive Value of Tests; ROC Curve; Respiratory Distress Syndrome; Retrospective Studies; Risk Factors; Time Factors
PubMed: 32326923
DOI: 10.1186/s12890-020-1131-0 -
International Journal For Parasitology Nov 2020Naturally acquired iummunity against clinical malaria is slow to develop, taking years of repeated exposure to parasites to acquire sufficiently broad and potent... (Review)
Review
Naturally acquired iummunity against clinical malaria is slow to develop, taking years of repeated exposure to parasites to acquire sufficiently broad and potent antibody responses. Increasing evidence suggests that Plasmodium infection and the resulting immune stimulation contribute to changes in the B cell compartment. In particular, accumulation of atypical memory B cells (atMBCs) is common in Plasmodium-exposed individuals. Similarities to B cell subsets present in other acute and chronic disease settings have provided insight into the development and potential function of these cells; however, their contribution to protection against malaria is still poorly understood. Here, we discuss recent findings that have increased our understanding of atMBCs and outline outstanding questions related to their function and development in the protective immune response to malaria.
Topics: Antibodies, Protozoan; B-Lymphocytes; Humans; Immunologic Memory; Malaria; Plasmodium
PubMed: 32987039
DOI: 10.1016/j.ijpara.2020.08.003 -
Current Opinion in Immunology Aug 2015Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of... (Review)
Review
Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), in discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; HIV Infections; Humans; Immune Evasion
PubMed: 26056742
DOI: 10.1016/j.coi.2015.05.007 -
Clinical and Experimental Immunology Dec 2022Memory B cells (MBCs) are an essential part of our immunological memory. They respond fast upon re-encountering pathogens and can differentiate into plasma cells that... (Review)
Review
Memory B cells (MBCs) are an essential part of our immunological memory. They respond fast upon re-encountering pathogens and can differentiate into plasma cells that secrete protective antibodies. The focus of this review is on MBCs that lack, or express low levels of, CD21, hereafter referred to as CD21-/low. These cells are expanded in peripheral blood with age and during chronic inflammatory conditions such as viral infections, malaria, common variable immunodeficiency, and autoimmune diseases. CD21-/low MBCs have gained significant attention; they produce disease-specific antibodies/autoantibodies and associate with key disease manifestations in some conditions. These cells can be divided into subsets based on classical B-cell and other markers, e.g. CD11c, FcRL4, and Tbet which, over the years, have become hallmarks to identify these cells. This has resulted in different names including age-associated, autoimmune-associated, atypical, tissue-like, tissue-resident, tissue-restricted, exhausted, or simply CD21-/low B cells. It is however unclear whether the expanded 'CD21-/low' cells in one condition are equivalent to those in another, whether they express an identical gene signature and whether they have a similar function. Here, we will discuss these issues with the goal to understand whether the CD21-/low B cells are comparable in different conditions.
Topics: Humans; B-Lymphocytes; Autoantibodies; Autoimmune Diseases; Malaria; Receptors, Complement 3d
PubMed: 36380692
DOI: 10.1093/cei/uxac103 -
PloS One 2016Typical and atypical optic neuritis (ON) are two clinical types of autoimmune inflammatory diseases of the optic nerve that causes acute vision loss, and are difficult...
BACKGROUND
Typical and atypical optic neuritis (ON) are two clinical types of autoimmune inflammatory diseases of the optic nerve that causes acute vision loss, and are difficult to distinguish in their early stages. The disturbance in the balance of Th17 and Treg lymphocytes is thought to play an essential role in these autoimmune inflammatory diseases.
OBJECTIVES
To detect the clinical relevance of Th17 and Treg in peripheral blood and the ratio of Treg/Th17 in patients with typical and atypical ON. To determine whether analysis of Th17 and Treg lymphocytes will provides insights into the different disease phenotypes of typical and atypical ON.
METHODS
We studied a consecutive series of patients aged 14-70 years who presented to our neurological department with typical ON (n = 30) or atypical ON (n = 33) within 4 weeks of their acute attacks. Routine clinical tests and ophthalmological examination were performed in all patients. Blood samples were collected from untreated patients and from gender- and age-matched healthy controls (n = 30). The proportion of peripheral blood Th17 cells and Treg cells was determined by flow cytometry.
RESULTS
Patients with atypical ON had a higher proportion of Th17 cells than patients with typical ON (3.61 ± 1.56 vs 2.55 ± 1.74, P<0.01) or controls (1.45 ± 0.86, P<0.01). The proportion of Th17 cells in patients with typical ON was also markedly higher than in controls (P<0.01). The mean percentage of Treg cells in atypical ON (6.31 ± 2.11) and typical ON (6.80 ± 2.00) were significantly lower when compared to controls (8.29 ± 2.32, both P<0.01). No significant difference in Treg frequency was observed between typical ON and atypical ON (p>0.05).
CONCLUSIONS
The frequency of Th17 cells is higher in atypical ON than typical ON, and patients with atypical ON have a greater imbalance of pro-inflammatory and regulatory cells than patients with typical ON when compared with controls. These changes are indicative of distinct pathological mechanisms and may provide useful information to distinguish typical and atypical ON.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Optic Neuritis; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 26785053
DOI: 10.1371/journal.pone.0146270 -
PLoS Pathogens Nov 2022The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and...
The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242.
Topics: Child; Humans; CD8-Positive T-Lymphocytes; COVID-19; Lupus Erythematosus, Systemic; Systemic Inflammatory Response Syndrome
PubMed: 36322537
DOI: 10.1371/journal.ppat.1010915 -
Malaria Journal Nov 2021Chronic and frequently recurring infectious diseases, such as malaria, are associated with expanded populations of atypical memory B cells (MBCs). These cells are...
BACKGROUND
Chronic and frequently recurring infectious diseases, such as malaria, are associated with expanded populations of atypical memory B cells (MBCs). These cells are different from classical MBCs by the lack of surface markers CD21 and CD27 and increased expression of inhibitory receptors, such as FcRL5. While the phenotype and conditions leading to neogenesis of atypical MBCs in malaria-experienced individuals have been studied extensively, the origin of these cells remains equivocal. Functional similarities between FcRL5 atypical MBCs and FcRL5 classical MBCs have been reported, suggesting that these cells may be developmentally related.
METHODS
Here, a longitudinal analysis of FcRL5 expression in various B cell subsets was performed in two children from a high transmission region in Uganda over a 6-month period in which both children experienced a malaria episode. Using B-cell receptor (BCR)-sequencing to track clonally related cells, the connections between IgM and IgG atypical MBCs and other B cell subsets were studied.
RESULTS
The highest expression of FcRL5 was found among IgG atypical MBCs, but FcRL5 cells were present in all MBC subsets. Following malaria, FcRL5 expression increased in all IgM MBC subsets analysed here: classical, activated, and atypical MBCs, while results for IgG MBC subsets were inconclusive. IgM atypical MBCs showed few connections with other B cell subsets, higher turnover than IgG atypical MBCs, and were predominantly derived from naïve B cells and FcRL5 IgM classical MBCs. In contrast, IgG atypical MBCs were clonally expanded and connected with classical MBCs. IgG atypical MBCs present after a malaria episode mainly originated from FcRL5 IgG classical MBCs.
CONCLUSIONS
Collectively, these results suggest fundamental differences between unswitched and class-switched B cell populations and provide clues about the primary developmental pathways of atypical MBCs in malaria-experienced individuals.
Topics: B-Lymphocytes; Child, Preschool; Chronic Disease; Humans; Immunoglobulin G; Immunoglobulin M; Longitudinal Studies; Malaria; Receptors, Fc; Recurrence
PubMed: 34758841
DOI: 10.1186/s12936-021-03970-1 -
Journal of Cutaneous Pathology Nov 2020Atypical cutaneous lymphoid infiltrates are challenging lesions in dermatopathology. We present a summary of the literature regarding kappa and lambda... (Review)
Review
BACKGROUND
Atypical cutaneous lymphoid infiltrates are challenging lesions in dermatopathology. We present a summary of the literature regarding kappa and lambda immunohistochemistry (IHC) and in situ hybridization (ISH) in the evaluation of atypical cutaneous or mucosal lymphoid infiltrates.
METHODS
Relevant articles from 1967 to 2018 in the English language were identified and summarized. In the absence of larger studies, case series of n ≥ 3 were included.
RESULTS
Sixty-three articles assessing kappa and lambda IHC and/or ISH were identified. Most focused on marginal zone lymphomas. Other lymphomas included follicle center lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma, plasmablastic lymphoma, multiple myeloma, monoclonal gammopathy of undetermined significance, and polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS). Non-neoplastic lesions included reactive lymphoid hyperplasia, cutaneous plasmacytosis, connective tissue disease, IgG4-related disease, acrodermatitis chronic atrophicans, Zoon balanitis, dermatitides, and infiltrates around epithelial dysplasias/neoplasias.
CONCLUSION
Kappa and lambda IHC and ISH are useful tools in the evaluation of cutaneous B-cell lymphomas and plasma cell neoplasms. The literature supports that the detection of light-chain restriction by IHC and ISH is one of the most useful findings in the differential diagnosis of reactive lymphoid hyperplasia vs B-cell lymphoma with plasmacytic differentiation.
Topics: Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunohistochemistry; In Situ Hybridization; Lymphocytes; Skin Diseases
PubMed: 32870521
DOI: 10.1111/cup.13858 -
Frontiers in Immunology 2022Studies have confirmed the involvement of a variety of lymphocyte subsets, including type 2 helper T lymphocytes (Th2) and IgG4 B lymphocytes, in the pathogenesis of... (Review)
Review
Studies have confirmed the involvement of a variety of lymphocyte subsets, including type 2 helper T lymphocytes (Th2) and IgG4 B lymphocytes, in the pathogenesis of IgG4-related disease (IgG4-RD). Those lymphocytes contribute to the major pathogenetic features of IgG4-RD. However, they are not the only cellular components in the immunoinflammatory environment of this mysterious disease entity. Recent studies have suggested that various non-lymphocytic components, including macrophages and fibroblasts, may also play an important role in the pathogenetic process of IgG4-RD in terms of contributing to the chronic and complex progress of the disease. Therefore, the potential role of non-lymphocyte in the pathogenesis of IgG4-RD is worth discussing.
Topics: B-Lymphocytes; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Macrophages; Th2 Cells
PubMed: 35967331
DOI: 10.3389/fimmu.2022.940581 -
Cell Reports Aug 2022Stimulatory type 1 conventional dendritic cells (cDC1s) engage in productive interactions with CD8 effectors along tumor-stroma boundaries. The paradoxical accumulation...
Stimulatory type 1 conventional dendritic cells (cDC1s) engage in productive interactions with CD8 effectors along tumor-stroma boundaries. The paradoxical accumulation of "poised" cDC1s within stromal sheets is unlikely to simply reflect passive exclusion from tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling generates developmentally conserved cell fate cues that regulate cDC1 behavior. We find that, in human T cell-inflamed tumors, CD8 T cells penetrate tumor nests, whereas cDC1s are confined within adjacent stroma that recurrently displays site-specific proteolysis of the matrix proteoglycan versican (VCAN), an essential organ-sculpting modification in development. VCAN is necessary, and its proteolytic fragment (matrikine) versikine is sufficient for cDC1 accumulation. Versikine does not influence tumor-seeding pre-DC differentiation; rather, it orchestrates a distinctive cDC1 activation program conferring exquisite sensitivity to DNA sensing, supported by atypical innate lymphoid cells. Thus, peritumoral stroma mimicking embryonic provisional matrix remodeling regulates cDC1 abundance and activity to elicit T cell-inflamed tumor microenvironments.
Topics: CD8-Positive T-Lymphocytes; Dendritic Cells; Humans; Immunity, Innate; Lymphocytes; Neoplasms; Tumor Microenvironment; Versicans
PubMed: 35977482
DOI: 10.1016/j.celrep.2022.111201