A Rare Cause of Double Negative αβ T Cell Lymphocytosis.
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PROVIDER: S-EPMC8239097 | BioStudies |
REPOSITORIES: biostudies
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Project description:BACKGROUND/AIMS:Chronic natural killer lymphocytosis (CNKL) has been associated with systemic autoimmunity; however, its association with scleritis or ocular autoimmunity has not been characterised. The natural killer (NK) cell function and immunophenotype of a patient with CNKL who developed bilateral scleritis and multiple systemic autoimmune findings were evaluated. METHODS:The ophthalmic records of a patient with CNKL and scleritis were reviewed over a 6-year period. Flow cytometry was performed to evaluate T cell, NK and B cell populations. NK cellular functions (ie, NK cytotoxicity and cytokine/chemokine production following interleukin 2 (IL2) stimulation) were evaluated. RESULTS:A 56-year-old woman with vitiligo, psoriatic arthritis, thyroiditis, erythema nodosum, bilateral anterior scleritis and Sjogren syndrome was managed with multiple immunosuppressive medications, including prednisone, mycophenolate mofetil and methotrexate. Flow cytometry showed a persistent elevation of CD56(+)CD3(-) NK cells greater than 40%, which was consistent with CNKL. NK cell cytotoxicity assay identified a deficiency of K562 cell lysis in the patient (1.46 mean-fold greater in control vs patient). NK cytokine/chemokine production following IL2 stimulation was also deficient (2.5-32.5-fold greater in control). Cytokines/chemokines assessed included pro-inflammatory (interferon gamma, tumor necrosis factor alpha, IL1, monocyte chemotactic protein 1) and immunoregulatory cytokines (IL4, IL5 and IL10). An abnormal elevation of TCRalpha/beta(+) CD3(+)CD4(-)CD8(-) T cells suggestive of autoimmune lymphoproliferative syndrome was observed; however, apoptosis dysfunction was not found. CONCLUSION:The association of increased but dysfunctional NK cells in the context of multiple systemic and ocular manifestations suggests a role of NK cells in the pathogenesis of our patient's disease. Further studies regarding NK cell dysfunction and ocular autoimmunity are needed.
| S-EPMC3172679 | BioStudies
Project description:<b>Background: </b>English bulldogs disproportionally develop an expansion of small B-cells, which has been interpreted as B-cell chronic lymphocytic leukemia (BCLL). However, clonality testing in these cases has often not been supportive of neoplasia.<br><br><b>Hypothesis: </b>English bulldogs have a syndrome of nonneoplastic B-cell expansion.<br><br><b>Animals: </b>Eighty-four English bulldogs with small-sized CD21+ B-cell lymphocytosis in the blood as determined by flow cytometry.<br><br><b>Methods: </b>This is a retrospective study. We characterized this syndrome by assessing B-cell clonality, clinical presentation, flow cytometric features, and immunoglobulin gammopathy patterns. We identified 84 cases with CD21+ lymphocytosis among 195 English bulldogs with blood samples submitted to the Colorado State University-Clinical Immunology laboratory for immunophenotyping between 2010 and 2019. Flow cytometry features were compared to normal B-cells and BCLL cases. PCR for antigen receptor rearrangements (PARR) by multiple immunoglobulin primers was performed to assess B-cell clonality. A subset of cases with gammopathy were examined by protein electrophoresis, immunofixation, and immunoglobulin subclass ELISA quantification.<br><br><b>Results: </b>Seventy percent (58/83) of cases had polyclonal or restricted polyclonal immunoglobulin gene rearrangements, suggesting nonmalignant B-cell expansion. The median age of all dogs in the study was 6.8?years and 74% were male. The median (range) lymphocyte count was 22?400/?L (2000-384?400/?L) and B-cells had low expression of class II MHC and CD25. Splenomegaly or splenic masses were detected in 57% (26/46) of cases and lymphadenopathy in 11% (7/61). Seventy-one percent (52/73) of cases had hyperglobulinemia and 77% (23/30) with globulin characterization had IgA?±?IgM polyclonal or restricted polyclonal gammopathy patterns.<br><br><b>Conclusions and clinical importance: </b>Polyclonal B-cell lymphocytosis in English bulldogs is characterized by low B-cell class II MHC and CD25 expression, splenomegaly and hyperglobulinemia consisting of increased IgA?±?IgM. We hypothesize that this syndrome has a genetic basis.
| S-EPMC7694837 | BioStudies
Project description:<h4>Background</h4>The prevalence of culture negative infective endocarditis (IEC) is reported as 2-7% though this figure may be as high as 70% in developing countries.<sup>1</sup> This higher rate will, at least in part, be due to reduced diagnostic facilities though some data suggests higher rates even when appropriate cultures were taken. The frequency is significantly elevated in patients who have already been exposed to antibiotics prior to blood cultures.<sup>1</sup> <sup>,</sup> <sup>2</sup> A rare cause of culture negative IEC is the HACEK group of organisms that are normal habitants of the oropharyngeal flora and account for 1-3% of native valve endocarditis.<sup>3</sup> <i>Aggregatibacter aphrophilus</i> (A. aphrophilus) is a member of the HACEK group of organisms.<h4>Case summary</h4>A 32-year-old gentleman with a previous bioprosthetic aortic valve presented with a 1-week history of diarrhoea, vomiting, malaise, and weight loss. He was awaiting redo surgery for stenosis of the bioprosthesis, which had been inserted aged 17 for aortic stenosis secondary to a bicuspid valve. The initial blood tests revealed liver and renal impairment with anaemia. A transoesophageal echocardiogram demonstrated a complex cavitating aortic root abscess, complicated by perforation into the right ventricle. He underwent emergency redo surgery requiring debridement of the aortic abscess, insertion of a mechanical aortic prosthesis (St Jude Medical, USA), annular reconstruction and graft replacement of the ascending aorta. Despite antibiotic therapy, he remained septic with negative blood and tissue cultures. Bacterial 16S rRNA gene sequencing confirmed <i>A. aphrophilus</i> infection, for which intravenous ceftriaxone was initiated. This was subsequently changed to ciprofloxacin due to neutropenia. The patient self-discharged from the hospital during the third week of antibiotic therapy. One week later, he was re-admitted with fever, night sweats, and dyspnoea. Transthoracic echocardiogram revealed a large recurrent aortic abscess cavity around the aortic annulus fistulating into the right heart chambers; this was confirmed by a computed tomography scan. There was dehiscence of the patch repair. Emergency redo aortic root replacement (25?mm mechanical valve conduit, ATS Medical, USA) and annular reconstruction was performed with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. VA-ECMO was weaned after 3 days. The patient completed a full course of intravenous meropenem and ciprofloxacin and made a good recovery.<h4>Discussion</h4>IEC with oropharyngeal HACEK organisms is rare and difficult to diagnose, due to negative blood culture results. The broad-range polymerase chain reaction and gene sequencing with comparison to the DNA database is useful in these circumstances. This case demonstrates the importance of the 16S rRNA gene sequencing for HACEK infection diagnosis and appropriate antibiotic treatment.
| S-EPMC7898661 | BioStudies
Project description:Postpartum women can develop headache, and their assessment requires a thorough and multidisciplinary approach. If the headache is unresponsive to treatment and accompanied by neurological deficit, neuroimaging needs to be undertaken to rule out other life-threatening causes. 1 We present a case of 35-year-old woman with pre-eclampsia and diet-controlled gestational diabetes mellitus, who had normal vaginal delivery at 40 weeks. She had an epidural analgesia for pain relief during labour, but had inadvertent dural puncture during the procedure and developed headache 24?hours after delivery. The headache was managed conservatively and she was discharged home, but was readmitted 8 days later with worsening headache. The headache was postural on admission but became continuous, developed neurological symptoms in the form of ataxic hemiparesis and convulsions. After neuroimaging, she was found to have cerebral venous sinus thrombosis. She was commenced on anticoagulants and anticonvulsants and made a complete recovery.
| S-EPMC5878351 | BioStudies
Project description:A 20-year-old female presented with a pulsatile neck mass. On evaluation, she was found to have right cervical aortic arch, which is a rare anomaly. We highlight the conventional and Computed tomography angiography features of this vascular anomaly.
| S-EPMC3634261 | BioStudies
Project description:Noncompaction cardiomyopathy (NCCM) is a rare but important cause of heart failure. The reported prevalence of left ventricle NCCM based on echocardiographic criteria varies between 0.014% and 1.3%, while the biventricular involvement is extremely rare with only few cases reported.
| S-EPMC5986029 | BioStudies
Project description:Monoclonal B-cell lymphocytosis (MBL) is a preclinical hematologic syndrome characterized by small accumulations of CD5(+) B lymphocytes. Most MBL share phenotypic characteristics with chronic lymphocytic leukemia (CLL). Although some MBL progress to CLL, most MBL have apparently limited potential for progression to CLL, particularly those MBL with normal absolute B-cell counts ('low-count' MBL). Most CLL are monoclonal and it is not known whether MBL are monoclonal or oligoclonal; this is important because it is unclear whether MBL represent indolent CLL or represent a distinct premalignant precursor before the development of CLL. We used flow cytometry analysis and sorting to determine immunophenotypic characteristics, clonality and molecular features of MBL from familial CLL kindreds. Single-cell analysis indicated four of six low-count MBL consisted of two or more unrelated clones; the other two MBL were monoclonal. 87% of low-count MBL clones had mutated immunoglobulin genes, and no immunoglobulin heavy-chain rearrangements of V(H) family 1 were observed. Some MBL were diversified, clonally related populations with evidence of antigen drive. We conclude that although low-count MBL share many phenotypic characteristics with CLL, many MBL are oligoclonal. This supports a model for step-wise development of MBL into CLL.
| S-EPMC2806490 | BioStudies
Project description:Numerous studies reported a small subpopulation of TCRαβ<sup>+</sup>CD4<sup>-</sup>CD8<sup>-</sup> (double-negative) T cells that exert regulatory functions in the peripheral lymphocyte population. However, the origin of these double-negative T (DNT) cells is controversial. Some researchers reported that DNT cells originated from the thymus, and others argued that these cells are derived from peripheral immune induction. We report a possible mechanism for the induction of nonregulatory CD4<sup>+</sup> T cells to become regulatory double-negative T (iDNT) cells <i>in vitro</i>. We found that immature bone marrow dendritic cells (CD86<sup>+</sup>MHC-II<sup>-</sup> DCs), rather than mature DCs (CD86<sup>+</sup>MHC-II<sup>+</sup>), induced high levels of iDNT cells. The addition of an anti-MHC-II antibody to the CD86<sup>+</sup>MHC-II<sup>+</sup> DC group significantly increased induction. These iDNT cells promoted B cell apoptosis and inhibited B cell proliferation and plasma cell formation. A subgroup of iDNT cells expressed NKG2D. Compared to NKG2D<sup>-</sup> iDNT cells, NKG2D<sup>+</sup> iDNT cells released more granzyme B to enhance B cell regulation. This enhancement may function <i>via</i> NKG2D ligands expressed on B cells following lipopolysaccharide stimulation. These results demonstrate that MHC-II impedes induction, and iDNT cells may be MHC independent. NKG2D expression on iDNT cells enhanced the regulatory function of these cells. Our findings elucidate one possible mechanism of the induction of peripheral immune tolerance and provide a potential treatment for chronic allograft rejection in the future.
| S-EPMC8242353 | BioStudies
Project description:Nuclear factor-?B (NF-?B) controls genes involved in normal lymphocyte functions, but constitutive NF-?B activation is often associated with B cell malignancy. Using high-throughput whole transcriptome sequencing, we investigated a unique family with hereditary polyclonal B cell lymphocytosis. We found a novel germline heterozygous missense mutation (E127G) in affected patients in the gene encoding CARD11, a scaffolding protein required for antigen receptor (AgR)-induced NF-?B activation in both B and T lymphocytes. We subsequently identified a second germline mutation (G116S) in an unrelated, phenotypically similar patient, confirming mutations in CARD11 drive disease. Like somatic, gain-of-function CARD11 mutations described in B cell lymphoma, these germline CARD11 mutants spontaneously aggregate and drive constitutive NF-?B activation. However, these CARD11 mutants rendered patient T cells less responsive to AgR-induced activation. By reexamining this rare genetic disorder first reported four decades ago, our findings provide new insight into why activating CARD11 mutations may induce B cell expansion and preferentially predispose to B cell malignancy without dramatically perturbing T cell homeostasis.
| S-EPMC3501355 | BioStudies
Project description:αβ lineage T cells, most of which are CD4<sup>+</sup> or CD8<sup>+</sup> and recognize MHC I- or MHC II-presented antigens, are essential for immune responses and develop from CD4<sup>+</sup>CD8<sup>+</sup> thymocytes. The absence of in vitro models and the heterogeneity of αβ thymocytes have hampered analyses of their intrathymic differentiation. Here, combining single-cell RNA and ATAC (chromatin accessibility) sequencing, we identified mouse and human αβ thymocyte developmental trajectories. We demonstrated asymmetric emergence of CD4<sup>+</sup> and CD8<sup>+</sup> lineages, matched differentiation programs of agonist-signaled cells to their MHC specificity, and identified correspondences between mouse and human transcriptomic and epigenomic patterns. Through computational analysis of single-cell data and binding sites for the CD4<sup>+</sup>-lineage transcription factor Thpok, we inferred transcriptional networks associated with CD4<sup>+</sup>- or CD8<sup>+</sup>-lineage differentiation, and with expression of Thpok or of the CD8<sup>+</sup>-lineage factor Runx3. Our findings provide insight into the mechanisms of CD4<sup>+</sup> and CD8<sup>+</sup> T cell differentiation and a foundation for mechanistic investigations of αβ T cell development.
| S-EPMC8641659 | BioStudies