scholarly journals Encephalomyelitis Caused by Balamuthia mandrillaris in a Woman With Breast Cancer: A Case Report and Review of the Literature

2022 ◽  
Vol 12 ◽  
Author(s):  
Juan Hu ◽  
Yiqi Zhang ◽  
Yongwei Yu ◽  
Huili Yu ◽  
Siruo Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Mycobacterium Abscessus ◽  
Review Of The Literature ◽  
Balamuthia Mandrillaris ◽  
Brain Infection ◽  
Granulomatous Amoebic Encephalitis ◽  
Brain And Spinal Cord ◽  
Generation Sequencing

Balamuthia mandrillaris is one cause of a rare and severe brain infection called granulomatous amoebic encephalitis (GAE), which has a mortality rate of >90%. Diagnosis of Balamuthia GAE is difficult because symptoms are non-specific. Here, we report a case of Balamuthia amoebic encephalomyelitis (encephalitis and myelitis) in a woman with breast cancer. She sustained trauma near a garbage dump 2 years ago and subsequently developed a skin lesion with a Mycobacterium abscessus infection. She experienced dizziness, lethargy, nausea and vomiting, inability to walk, and deterioration of consciousness. Next-generation sequencing of cerebrospinal fluid (CSF) samples revealed B. mandrillaris, and MRI of both brain and spinal cord showed abnormal signals. T-cell receptor (TCR) sequencing of the CSF identified the Top1 TCR. A combination of amphotericin B, flucytosine, fluconazole, sulfamethoxazole, trimethoprim, clarithromycin, pentamidine, and miltefosine was administrated, but she deteriorated gradually and died on day 27 post-admission.

scholarly journals Immortalization and Functional Screening of Natively Paired Human T Cell Receptor Repertoires

2021 ◽  
Author(s):  
Ahmed S Fahad ◽  
Cheng Yu Chung ◽  
Sheila N. Lopez Acevedo ◽  
Nicoleen Boyle ◽  
Bharat Madan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Functional Screening ◽  
Next Generation ◽  
Sequencing Technologies ◽  
Human T Cell ◽  
Screening Platform ◽  
Generation Sequencing

Functional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major histocompatibility complex (pMHC) specificity of individual TCRs. Here we developed a new high-throughput approach to enable repertoire-scale functional evaluations of natively paired TCRs. In particular, we leveraged the immortalized nature of physically linked TCRα:β amplicon libraries to analyze binding against multiple recombinant pMHCs on a repertoire scale. To exemplify the utility of this approach, we also performed affinity-based functional mapping in conjunction with quantitative next-generation sequencing to track antigen- specific TCRs. These data successfully validated a new immortalization and screening platform to facilitate detailed molecular analyses of human TCRs against diverse antigen targets associated with health, vaccination, or disease.

scholarly journals T-cell receptor-α repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing

Haematologica ◽  
2018 ◽  
Vol 104 (3) ◽  
pp. 622-631 ◽  
Author(s):  
Cornelia S. Link-Rachner ◽  
Anne Eugster ◽  
Elke Rücker-Braun ◽  
Falk Heidenreich ◽  
Uta Oelschlägel ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Next Generation Sequencing ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Receptor ◽  
Generation Sequencing

scholarly journals THER-06. GENOMIC AND IMMUNE CHARACTERIZATION OF TRIPLE NEGATIVE BREAST CANCER BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i11-i12
Author(s):  
Benjamin Vincent ◽  
Maria Sambade ◽  
Shengjie Chai ◽  
Marni Siegel ◽  
Luz Cuaboy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Brain Metastases ◽  
T Cell Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Receptor ◽  
Gene Signature ◽  
Specific Response ◽  
Immune Gene

Abstract INTRODUCTION: Approximately 50% of patients with metastatic triple negative breast cancer (TNBC) will develop brain metastases (BM). Routinely treated with radiotherapy and/or surgery, survival is generally less than one year. There are no approved systemic therapies to treat TNBC BM. We characterized the genomic and immune landscape of TNBC BM to foster the development of effective brain permeable anti-cancer agents, including immunotherapy. EXPERIMENTAL PROCEDURES: A clinically-annotated BCBM biobank of archival tissues was created under IRB approval. DNA (tumor/normal) and RNA (tumor) were extracted from TNBC primaries and BM; whole exome (WES) and RNA sequencing (RNASeq) was performed. Mutations were determined from WES as those co-identified by two variant callers (Strelka|Cadabra). Immune gene signature expression, molecular subtype identification, and T cell receptor repertoires were inferred from RNAseq. RESULTS: 32 TNBC patient tissues (14 primaries, 18 BCBM, 6 primary-BCBM matched), characterized as basal-like by PAM50, were analyzed. Top exome mutation calls included ten genes in ≥19% of BCBMs including TP53, ATM, and PIK3R1, and four genes in ≥18% of primaries including TP53 and PIK3R1. Many immune gene signatures were lower in BM compared to primaries including B cell, dendritic cell, regulatory T cell, and IgG cluster (p< 0.05). A signature of PD-1 inhibition responsiveness was higher in BM compared with primaries (p< 0.05). BCBM T cell receptor repertoires showed higher evenness and lower read count (both p < 0.01) compared to primaries. CONCLUSIONS: TNBC BM compared to primaries that metastasize to the brain show lower immune gene signature expression, higher PD-1 inhibition response signature expression, and T cell receptor repertoire features less characteristic of an active antigen-specific response. Mutations common to TNBC BM and primaries include TP53 and PIK3R1. Given that non-BCBM (i.e. lung and melanoma) show response to checkpoint inhibitors, these findings collectively support further study of immunotherapy for TNBC BM.

scholarly journals Preparing Unbiased T-Cell Receptor and Antibody cDNA Libraries for the Deep Next Generation Sequencing Profiling

2013 ◽  
Vol 4 ◽  
Author(s):  
Ilgar Z. Mamedov ◽  
Olga V. Britanova ◽  
Ivan V. Zvyagin ◽  
Maria A. Turchaninova ◽  
Dmitriy A. Bolotin ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cdna Libraries ◽  
Next Generation ◽  
Generation Sequencing

Balamuthia mandrillaris-Related Primary Amoebic Encephalitis in China Diagnosed by Next Generation Sequencing and a Review of the Literature

2019 ◽  
Author(s):  
Yinan Yang ◽  
Xiaobin Hu ◽  
Li Min ◽  
Xiangyu Dong ◽  
Yuanlin Guan
Keyword(s):  
Next Generation Sequencing ◽  
Inflammatory Diseases ◽  
Clinical Manifestations ◽  
Infectious Agent ◽  
Disease Diagnosis ◽  
Rapid Identification ◽  
Next Generation ◽  
Balamuthia Mandrillaris ◽  
Granulomatous Amoebic Encephalitis ◽  
Generation Sequencing

Abstract Background Encephalitis is caused by infection, immune mediated diseases, or primary inflammatory diseases. Of all the causative infectious pathogens, 90% are viruses or bacteria. Granulomatous amoebic encephalitis (GAE), caused by Balamuthia mandrillaris, is a rare but life-threatening disease. Diagnosis and therapy are frequently delayed due to the lack of specific clinical manifestations. Method A healthy 2 year old Chinese male patient initially presented with a nearly 2 month history of irregular fever. We present this case of granulomatous amoebic encephalitis caused by B. mandrillaris. Next generation sequencing of the patient’s cerebrospinal fluid (CSF) was performed to identify an infectious agent. Result The results of next generation sequencing of the CSF showed that most of the mapped reads belonged to Balamuthia mandrillaris. Conclusion Next generation sequencing (NGS) is an unbiased and rapid diagnostic tool. The NGS method can be used for the rapid identification of causative pathogens. The NGS method should be widely applied in clinical practice and help clinicians provide direction for the diagnosis of diseases, especially for rare and difficult cases.

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