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Frontiers in Immunology 2024Chagas disease is a neglected parasitic disease caused by . While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).
INTRODUCTION
Chagas disease is a neglected parasitic disease caused by . While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).
METHODS
Here, we employed high-dimensional flow cytometry to analyze CD4 T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms.
RESULTS
Effector CD27CD4 T cells were expanded in both CCC groups, and only mild CCC patients showed higher frequencies of effector memory and T follicular helper (Tfh) cells than healthy donors (CTL) and asymptomatic patients. Unsupervised analysis confirmed these findings and further revealed the expansion of a specific subpopulation composed of Tfh, transitional, and central memory CD4 T cells bearing a phenotype associated with strong activation, differentiation, and exhaustion in patients with mild but not moderate/severe CCC. In contrast, patients with mild and moderate/severe CCC had lower frequencies of CD4 T cells expressing lower levels of activation markers, suggesting resting status, than CTL. Regarding the B cell compartment, no alterations were found in naïve CD21, memory cells expressing IgM or IgD, marginal zone, and plasma cells in patients with Chagas disease. However, expansion of class-switched activated and atypical memory B cells was observed in all clinical forms, and more substantially in mild CCC patients.
DISCUSSION
Taken together, our results showed that infection triggers changes in CD4 T and B cell compartments that are more pronounced in the mild CCC clinical form, suggesting an orchestrated cellular communication during Chagas disease.
CONCLUSION
Overall, these findings reinforce the heterogeneity and complexity of the immune response in patients with chronic Chagas disease and may provide new insights into disease pathology and potential markers to guide clinical decisions.
Topics: Humans; Chagas Cardiomyopathy; Male; Middle Aged; Female; CD4-Positive T-Lymphocytes; Adult; B-Lymphocytes; Trypanosoma cruzi; Chronic Disease; Aged; Lymphocyte Activation
PubMed: 38726014
DOI: 10.3389/fimmu.2024.1385850 -
Journal of Cutaneous Pathology May 2024Mycosis fungoides (MF) represents the most common type of primary cutaneous T-cell lymphoma. Recognition of MF variants with divergent immunophenotypes is important for...
Mycosis fungoides (MF) represents the most common type of primary cutaneous T-cell lymphoma. Recognition of MF variants with divergent immunophenotypes is important for accurate diagnosis and appropriate management, as they can be confused with other lymphoma subtypes. We present a case of a 49-year-old male previously diagnosed with a cutaneous lymphoproliferative disorder with an unusual NK/T-cell phenotype. He presented with a 10-year history of pelvic girdle rash involving the right hip and upper thigh. The lesions were characterized as atrophic patches concentrated in sun-protected areas and involving 10% of the body surface area. Shave biopsies revealed an atypical epidermotropic infiltrate composed of hyperchromatic small to medium-sized lymphocytes with perinuclear halos and "tagging" along the dermal-epidermal junction. The immunophenotype was unusual in that the neoplastic lymphocytes showed complete loss of pan T-cell antigens along with expression of CD56, cytotoxic markers, and weak CD20. All other B-cell markers were negative. The combination of clinical findings, in addition to the histopathologic and immunophenotypic profile, were diagnostic of null T-cell phenotype MF with aberrant expression of CD56 and CD20. Null T-cell phenotype MF is very uncommon, can be diagnostically challenging, and can mislead the diagnosis of aggressive lymphoma subtypes.
PubMed: 38725374
DOI: 10.1111/cup.14643 -
Cell Reports. Medicine May 2024Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before...
Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8 T cell senescence, driven by atypical chemokine receptor 2 (ACKR2) CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2 tumor cells are induced to produce transforming growth factor β to drive CD8 T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8 T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2 tumor cells driving CD8 T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8 T cell senescence for chemoradiotherapy recurrence.
Topics: Humans; CD8-Positive T-Lymphocytes; Female; Uterine Cervical Neoplasms; Cellular Senescence; Chemoradiotherapy; Neoplasm Recurrence, Local; Animals; Mice; Cell Line, Tumor; Prognosis; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Transforming Growth Factor beta; T-Cell Senescence
PubMed: 38723624
DOI: 10.1016/j.xcrm.2024.101550 -
Frontiers in Immunology 2024Inhibitory natural killer (NK) cell receptors recognize MHC class I (MHC-I) in on target cells and suppress cytotoxicity. Some NK cell receptors recognize MHC-I in ,...
Inhibitory natural killer (NK) cell receptors recognize MHC class I (MHC-I) in on target cells and suppress cytotoxicity. Some NK cell receptors recognize MHC-I in , but the role of this interaction is uncertain. Ly49Q, an atypical Ly49 receptor expressed in non-NK cells, binds MHC-I in and mediates chemotaxis of neutrophils and type I interferon production by plasmacytoid dendritic cells. We identified a lipid-binding motif in the juxtamembrane region of Ly49Q and found that Ly49Q organized functional membrane domains comprising sphingolipids via sulfatide binding. Ly49Q recruited actin-remodeling molecules to an immunoreceptor tyrosine-based inhibitory motif, which enabled the sphingolipid-enriched membrane domain to mediate complicated actin remodeling at the lamellipodia and phagosome membranes during phagocytosis. Thus, Ly49Q facilitates integrative regulation of proteins and lipid species to construct a cell type-specific membrane platform. Other Ly49 members possess lipid binding motifs; therefore, membrane platform organization may be a primary role of some NK cell receptors.
Topics: Animals; Humans; Sphingolipids; Killer Cells, Natural; Phagocytosis; Phagocytes; NK Cell Lectin-Like Receptor Subfamily A; Cell Membrane; Protein Binding
PubMed: 38720899
DOI: 10.3389/fimmu.2024.1401294 -
The Journal of the Association of... Nov 2023: There is a clinical imperative to devise metrics to prognosticate dengue severity. Our objective was to determine the association between longitudinal trends in...
: There is a clinical imperative to devise metrics to prognosticate dengue severity. Our objective was to determine the association between longitudinal trends in atypical lymphocytes and large immature cell count with platelet count and dengue severity. : Retrospective analysis of longitudinally measured clinical and hematological data from ( = 79) hospitalized dengue patients was done. : The cohort consisted of patients with dengue fever without warning signs (DFWOWS) ( = 40, females = 14, and age = 19.9 ± 14.6 years), dengue fever with warning signs (DFWWS) ( = 36, females = 13, and age = 16.1 ± 14.1 years) and severe dengue ( = 3, females = 2, and age = 5.3 ± 4 years). Platelet count increased at a rate of 11,524 cells/mm/day, with a slower rate of rise as the severity increased ( = 0.001***). Concurrently hematocrit and neutrophil percentage decreased, while the lymphocyte percentage and white blood cell (WBC) count increased during the hospital stay. Every 1% increase in atypical lymphocyte count (ATY) was associated with a fall in platelet count by 16,963 cells/mm ( = 0.001***). A similar but weaker trend was found for large immature cells (LICs). : The data support the usefulness of longitudinal tracking of atypical lymphocyte and large immature cell count for dengue prognosis. The time trends of the hematological parameters indicate the progression of patients from the critical to the recovery phase. : Peraka R, Koppula A, Muppala BS, Utility of Atypical Lymphocytes and Large Immature Cells in Prediction of Dengue Severity. J Assoc Physicians India 2023;71(11):19-24.
Topics: Humans; Male; Retrospective Studies; Female; Severity of Illness Index; Dengue; Platelet Count; Young Adult; Adolescent; Lymphocytes; Adult; Lymphocyte Count; Child; Prognosis; Severe Dengue; Child, Preschool; Leukocyte Count
PubMed: 38720491
DOI: 10.59556/japi.71.0395 -
Indian Journal of Pathology &... Mar 2024Inflammation has an important role in the progression of endometrial carcinoma.
Diagnostic, prognostic, and predictive importance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and carcinoma.
BACKGROUND
Inflammation has an important role in the progression of endometrial carcinoma.
AIMS
The aim of this study is to find the association between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and endometrial carcinoma. The study also focuses on the association of CA125, NLR, and PLR with histopathological parameters in endometrial carcinoma that are of prognostic importance.
MATERIALS AND METHODS
This is a prospective cross-sectional study on 57 biopsy-proven cases of endometrial hyperplasia and carcinoma conducted over a period of two years. The NLR, PLR, and CA125 were calculated and recorded in all the 57 cases.
RESULTS
The 57 cases were divided into three groups: endometrial hyperplasia without atypia group which included 36 cases, endometrial atypical hyperplasia group which included 10 cases, and the endometrial carcinoma group which included 11 cases. Comparison was done between the groups, and parity, NLR, PLR, and CA125 were found to be significant, but patient age and postmenopausal status were not significant. NLR, PLR, and CA125 were found to increase with higher grade, pT-stage, and nodal stage for the endometrial carcinoma cases.
CONCLUSION
NLR, PLR, and CA125 were marginally increased or normal in the case of endometrial hyperplasia without atypia and endometrial atypical hyperplasia, while they were significantly increased in endometrial carcinoma, and also correlated with an increase in grade, pT-stage, and nodal stage. Hence, these can be considered for additional screening as diagnostic, prognostic, and predictive markers in case of abnormal uterine bleeding with endometrial pathology.
PubMed: 38718204
DOI: 10.4103/ijpm.ijpm_655_23 -
Translational Pediatrics Apr 2024Caroli syndrome or Caroli disease is characterized by focal dilation of the intrahepatic bile ducts, with or without congenital liver fibrosis. Mutations in the gene...
BACKGROUND
Caroli syndrome or Caroli disease is characterized by focal dilation of the intrahepatic bile ducts, with or without congenital liver fibrosis. Mutations in the gene can result in nephropathy, an autosomal recessive cystic kidney disease. However, this genetic mutation is clinically associated with Caroli syndrome or disease. We hypothesize that gene mutations may contribute to extrarenal phenotypes such as Caroli disease or syndrome.
CASE DESCRIPTION
The outpatient department received a 1-year-old male patient with persistent dilated bile ducts for over four months. Subsequent ultrasound examination revealed liver cirrhosis, splenomegaly, and cystic dilatation of the intrahepatic bile duct. He was subsequently admitted for comprehensive diagnosis and treatment. Accordingly, we performed computed tomography (CT)-hepatic portal venography, magnetic resonance-cholangiography, and the plain liver scan, the results revealed liver cirrhosis, splenomegaly, cystic dilatation of the intrahepatic bile duct, as well as atypical hyperplasia nodules in the right posterior lobe of the liver and lymphatic hyperplasia and enlargement in the porta hepatis and the space between the liver and stomach. As the possibility of early small liver cancer could not be excluded due to the presence of nodules, surgical resection was performed followed by pathological examination and whole genome exome testing. The pathological findings revealed hepatocyte swelling, hydropic degeneration, and sporadic necrosis. Fibrous tissue hyperplasia was observed in the portal vein area, along with local pseudolobule formation. Also, numerous small bile duct hyperplasia was observed with lymphocyte infiltration, which is consistent with cirrhosis. Moreover, the hepatocytes of the small focal area showed atypical hyperplasia. Considering the above findings, Caroli syndrome was diagnosed. The genetic results showed two heterozygous mutations in the gene, c.2290delC (p.Q764Nfs*29) and c.2401G>C (p.G801R). Therefore, the child's intrahepatic bile duct dilatation and cirrhosis were considered as the manifestations of Caroli syndrome caused by mutations in the gene.
CONCLUSIONS
Mutations in the gene can manifest as Caroli disease or Caroli syndrome. For the definite diagnosis of liver diseases of unknown etiology, whole exome sequencing may be more conducive.
PubMed: 38715676
DOI: 10.21037/tp-23-574 -
Frontiers in Immunology 2024B cells play a pivotal role in adaptive immunity which has been extensively characterised primarily via flow cytometry-based gating strategies. This study addresses the...
INTRODUCTION
B cells play a pivotal role in adaptive immunity which has been extensively characterised primarily via flow cytometry-based gating strategies. This study addresses the discrepancies between flow cytometry-defined B cell subsets and their high-confidence molecular signatures using single-cell multi-omics approaches.
METHODS
By analysing multi-omics single-cell data from healthy individuals and patients across diseases, we characterised the level and nature of cellular contamination within standard flow cytometric-based gating, resolved some of the ambiguities in the literature surrounding unconventional B cell subsets, and demonstrated the variable effects of flow cytometric-based gating cellular heterogeneity across diseases.
RESULTS
We showed that flow cytometric-defined B cell populations are heterogenous, and the composition varies significantly between disease states thus affecting the implications of functional studies performed on these populations. Importantly, this paper draws caution on findings about B cell selection and function of flow cytometric-sorted populations, and their roles in disease. As a solution, we developed a simple tool to identify additional markers that can be used to increase the purity of flow-cytometric gated immune cell populations based on multi-omics data (). Here, we demonstrate that additional non-linear CD20, CD21 and CD24 gating can increase the purity of both naïve and memory populations.
DISCUSSION
These findings underscore the need to reconsider B cell subset definitions within the literature and propose leveraging single-cell multi-omics data for refined characterisation. We show that single-cell multi-omics technologies represent a powerful tool to bridge the gap between surface marker-based annotations and the intricate molecular characteristics of B cell subsets.
Topics: Humans; Flow Cytometry; Single-Cell Analysis; B-Lymphocyte Subsets; B-Lymphocytes; Immunophenotyping; Biomarkers; Multiomics
PubMed: 38707902
DOI: 10.3389/fimmu.2024.1380386 -
BMC Immunology May 2024Breast cancer is the most common cancer in females. The immune system has a crucial role in the fight against cancer. B and T cells, the two main components of the...
BACKGROUND
Breast cancer is the most common cancer in females. The immune system has a crucial role in the fight against cancer. B and T cells, the two main components of the adaptive immunity, are critical players that specifically target tumor cells. However, B cells, in contrast to T cells, and their role in cancer inhibition or progression is less investigated. Accordingly, in this study, we assessed and compared the frequency of naïve and different subsets of memory B cells in the peripheral blood of patients with breast cancer and healthy women.
RESULTS
We found no significant differences in the frequencies of peripheral CD19 B cells between the patients and controls. However, there was a significant decrease in the frequency of CD19IgM B cells in patients compared to the control group (P=0.030). Moreover, the patients exhibited higher percentages of atypical memory B cells (CD19CD27IgM, P=0.006) and a non-significant increasing trend in switched memory B cells (CD19CD27IgM, P=0.074). Further analysis revealed a higher frequency of atypical memory B cells (aMBCs) in the peripheral blood of patients without lymph node involvement as well as those with a tumor size greater than 2cm or with estrogen receptor (ER) negative/progesterone receptor (PR) negative tumors, compared with controls (P=0.030, P=0.040, P=0.031 and P=0.054, respectively).
CONCLUSION
Atypical memory B cells (CD19CD27IgM) showed a significant increase in the peripheral blood of patients with breast cancer compared to the control group. This increase seems to be associated with tumor characteristics. Nevertheless, additional research is necessary to determine the precise role of these cells during breast cancer progression.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Adult; Lymph Nodes; Memory B Cells; Aged; Antigens, CD19; Immunologic Memory; Tumor Necrosis Factor Receptor Superfamily, Member 7; B-Lymphocyte Subsets
PubMed: 38702630
DOI: 10.1186/s12865-024-00620-4 -
International Journal of Surgical... Apr 2024In this study, we describe a patient of primary cutaneous acral CD8-positive lymphoproliferative disorder located in a nonacral region. A 65-year-old male presented with...
In this study, we describe a patient of primary cutaneous acral CD8-positive lymphoproliferative disorder located in a nonacral region. A 65-year-old male presented with an ill-defined lesion of rubbery consistency and a maximum diameter of 2.5 cm localized in the right thigh. Histologically, it was composed of a diffuse dermal infiltration of medium-sized atypical lymphocytes that expressed CD3, CD8, and TIA-1. In addition, a characteristic paranuclear positivity with CD68 was observed. During the follow-up, the patient had a recurrence of the disease in the abdomen with a lesion showing similar morphology and phenotype. To our knowledge, < 20 patients of primary cutaneous acral CD8-positive lymphoproliferative disorder with a nonacral presentation have been described in English literature. Although rare, its identification is essential to differentiate it from other T-cell lymphoma that express CD8 and cytotoxic markers, and whose clinical courses are very aggressive.
PubMed: 38689481
DOI: 10.1177/10668969241248587