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Article ; Online: MOG-IgA as a Potential Marker of Germinal Center Activity.

Handel, Adam E / Irani, Sarosh R / Leite, M Isabel

2024 Volume 81, Issue 3, Page(s) 297

MeSH term(s)	Humans ; Germinal Center ; Immunoglobulin A
Chemical Substances	Immunoglobulin A
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2023.5167
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Article ; Online: Erratum to: Bioinformatics Analysis of Estrogen-Responsive Genes.

Handel, Adam E

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1366, Page(s) E3

Language	English
Publishing date	2017-06-13
Publishing country	United States
Document type	Journal Article ; Published Erratum
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-3127-9_45
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Article ; Online: Changes in the Rate of Leucine-Rich Glioma-Inactivated 1 Seropositivity During the COVID-19 Lockdown.

Handel, Adam E / Palace, Jacqueline / Bateman, Elizabeth / Waters, Patrick / Irani, Sarosh R

JAMA neurology

2023 Volume 80, Issue 4, Page(s) 419–420

MeSH term(s)	Humans ; Leucine ; COVID-19 ; Communicable Disease Control ; Proteins ; Glioma
Chemical Substances	Leucine (GMW67QNF9C) ; Proteins
Language	English
Publishing date	2023-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2022.5346
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Article ; Online: The contribution of thymic tolerance to central nervous system autoimmunity.

Alberti, Piero / Handel, Adam E

Seminars in immunopathology

2020 Volume 43, Issue 1, Page(s) 135–157

Abstract: Autoimmune diseases of the central nervous system (CNS) are associated with high levels of morbidity and economic cost. Research efforts have previously focused on the contribution of the peripheral adaptive and innate immune systems to CNS autoimmunity. ...

Abstract	Autoimmune diseases of the central nervous system (CNS) are associated with high levels of morbidity and economic cost. Research efforts have previously focused on the contribution of the peripheral adaptive and innate immune systems to CNS autoimmunity. However, a failure of thymic negative selection is a necessary step in CNS-reactive T cells escaping into the periphery. Even with defective thymic or peripheral tolerance, the development of CNS inflammation is rare. The reasons underlying this are currently poorly understood. In this review, we examine evidence implicating thymic selection in the pathogenesis of CNS autoimmunity. Animal models suggest that thymic negative selection is an important factor in determining susceptibility to and severity of CNS inflammation. There are indirect clinical data that suggest thymic function is also important in human CNS autoimmune diseases. Specifically, the association between thymoma and paraneoplastic encephalitis and changes in T cell receptor excision circles in multiple sclerosis implicate thymic tolerance in these diseases. We identify potential associations between CNS autoimmunity susceptibility factors and thymic tolerance. The therapeutic manipulation of thymopoiesis has the potential to open up new treatment modalities, but a better understanding of thymic tolerance in CNS autoimmunity is required before this can be realised.
MeSH term(s)	Animals ; Autoimmune Diseases ; Autoimmunity ; Central Nervous System ; Humans ; Immune Tolerance ; T-Lymphocytes
Language	English
Publishing date	2020-10-27
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-020-00822-z
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Article ; Online: Comment on "Identification of an Intronic Regulatory Element Necessary for Tissue-Specific Expression of

Handel, Adam E / Holländer, Georg A

Journal of immunology (Baltimore, Md. : 1950)

2019 Volume 203, Issue 9, Page(s) 2355

MeSH term(s)	Epithelial Cells ; Introns ; Regulatory Sequences, Nucleic Acid
Language	English
Publishing date	2019-10-18
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1900948
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Article ; Online: Bioinformatics Analysis of Estrogen-Responsive Genes.

Handel, Adam E

Methods in molecular biology (Clifton, N.J.)

2015 Volume 1366, Page(s) 29–39

Abstract: Estrogen is a steroid hormone that plays critical roles in a myriad of intracellular pathways. The expression of many genes is regulated through the steroid hormone receptors ESR1 and ESR2. These bind to DNA and modulate the expression of target genes. ... ...

Abstract	Estrogen is a steroid hormone that plays critical roles in a myriad of intracellular pathways. The expression of many genes is regulated through the steroid hormone receptors ESR1 and ESR2. These bind to DNA and modulate the expression of target genes. Identification of estrogen target genes is greatly facilitated by the use of transcriptomic methods, such as RNA-seq and expression microarrays, and chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq). Combining transcriptomic and ChIP-seq data enables a distinction to be drawn between direct and indirect estrogen target genes. This chapter discusses some methods of identifying estrogen target genes that do not require any expertise in programming languages or complex bioinformatics.
MeSH term(s)	Animals ; Binding Sites ; Chromatin Immunoprecipitation ; Computational Biology ; Databases, Genetic ; Estrogen Receptor alpha/drug effects ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Estrogens/pharmacology ; Gene Expression Profiling/methods ; Gene Expression Regulation/drug effects ; Humans ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic ; Software ; User-Computer Interface ; Workflow
Chemical Substances	Estrogen Receptor alpha ; Estrogens
Language	English
Publishing date	2015-07-28
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-3127-9_4
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Article ; Online: Brachial Gunshot Wounds: Injury Patterns and Considerations for Managing the Abnormal Neurological Examination.

Chi, David / Tandon, Damini / Evans, Adam G / Brown, Danielle J / Payne, Rachael M / Van Handel, Amelia C / Shim, Kevin G / Mackinnon, Susan E / Pet, Mitchell A

Hand (New York, N.Y.)

2024 , Page(s) 15589447231221170

Abstract: Background: Nerve injuries from gunshot wounds (GSWs) to the upper arm can cause significant morbidity and loss of function. However, indications for surgical exploration and nerve reconstruction remain unclear as both low- and high-grade injuries can ... ...

Abstract	Background: Nerve injuries from gunshot wounds (GSWs) to the upper arm can cause significant morbidity and loss of function. However, indications for surgical exploration and nerve reconstruction remain unclear as both low- and high-grade injuries can present with an abnormal neurological examination. Methods: Adult patients presenting with a history of isolated GSW to the upper arm between 2010 and 2019 at a single urban level 1 trauma center were screened for inclusion in this retrospective study. Patient demographics, neurological examination findings, concurrent injuries, and intraoperative findings were gathered. Bivariate analysis was performed to characterize factors associated with nerve injuries. Results: There were 139 adult patients with isolated brachial GSWs, and 49 patients (35%) presented with an abnormal neurological examination and significantly associated with concurrent humerus fractures (39% vs 21%, Conclusion: Nerve injury from upper arm GSWs is common with directly traumatized nerves confirmed in at least 39% and nerve transection in at least 16% of patients with an abnormal neurological examination. Timely referral to a hand and/or peripheral nerve surgeon for close clinical follow-up, appropriate diagnosis, and any necessary surgical reconstruction with nerve grafts, tendon transfers, and nerve transfers is recommended.
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2277325-3
ISSN	1558-9455 ; 1558-9447
ISSN (online)	1558-9455
ISSN	1558-9447
DOI	10.1177/15589447231221170
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Article ; Online: Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis.

Kelly, Mark J / Grant, Eleanor / Murchison, Andrew G / Binks, Sophie / Ramanathan, Sudarshini / Michael, Sophia / Handel, Adam E / Handunnetthi, Lahiru / Uy, Christopher E / Soltys, John N / Dubey, Divyanshu / Day, Gregory S / Lopez-Chiriboga, A Sebastian / Flanagan, Eoin P / Sheerin, Fintan / Irani, Sarosh R

JAMA neurology

2024

Abstract: ... and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral ... LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings ... the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and ...

Abstract	Importance: Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy. Objective: To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD). Design, setting, and participants: This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023. Main outcomes and measures: MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features. Results: Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P < .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P < .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala. Conclusions and relevance: In this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.
Language	English
Publishing date	2024-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2024.0126
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Article ; Online: Fatigue predicts quality of life after leucine-rich glioma-inactivated 1-antibody encephalitis.

Binks, Sophie N M / Veldsman, Michele / Handel, Adam E / Jacob, Saiju / Maddison, Paul / Coebergh, Jan / Michael, Sophia / Ramanathan, Sudarshini / Easton, Ava / Nissen, Mette Scheller / Leite, Maria Isabel / Okai, David / Blaabjerg, Morten / Husain, Masud / Irani, Sarosh R

Annals of clinical and translational neurology

2024 Volume 11, Issue 4, Page(s) 1053–1058

Abstract: ... inactivated 1-antibody encephalitis (LGI1-Ab-E). From 60 patients, 85% (51 out of 60) showed one abnormal ... An abbreviated five-item battery explained most variance in QoL. Wide-ranging impacts post-LGI1-Ab-E include ...

Abstract	Patient-reported quality-of-life (QoL) and carer impacts are not reported after leucine-rich glioma-inactivated 1-antibody encephalitis (LGI1-Ab-E). From 60 patients, 85% (51 out of 60) showed one abnormal score across QoL assessments and 11 multimodal validated questionnaires. Compared to the premorbid state, QoL significantly deteriorated (p < 0.001) and, at a median of 41 months, fatigue was its most important predictor (p = 0.025). In total, 51% (26 out of 51) of carers reported significant burden. An abbreviated five-item battery explained most variance in QoL. Wide-ranging impacts post-LGI1-Ab-E include decreased QoL and high caregiver strain. We identify a rapid method to capture QoL in routine clinic or clinical trial settings.
MeSH term(s)	Humans ; Leucine ; Quality of Life ; Intracellular Signaling Peptides and Proteins ; Autoantibodies ; Encephalitis ; Glioma ; Fatigue/etiology
Chemical Substances	Leucine (GMW67QNF9C) ; Intracellular Signaling Peptides and Proteins ; Autoantibodies
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.52006
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Article ; Online: The role of thymic tolerance in CNS autoimmune disease.

Handel, Adam E / Irani, Sarosh R / Holländer, Georg A

Nature reviews. Neurology

2018 Volume 14, Issue 12, Page(s) 723–734

Abstract: The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for ...

Abstract	The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms ensure that cells with an overt autoreactive specificity are eliminated before they emigrate to the periphery and control the generation of thymic regulatory T cells. Evidence from animal studies demonstrates that thymic T cell selection is important for establishing tolerance to autoantigens. However, there is a considerable knowledge gap regarding the role of thymic selection in autoimmune conditions of the human CNS. In this Review, we critically examine the current body of experimental evidence for the contribution of thymic tolerance to CNS autoimmune diseases. An understanding of why dysfunction of either thymic or peripheral tolerance mechanisms rarely leads to CNS inflammation is currently lacking. We examine the potential of de novo T cell formation and thymic selection as novel therapeutic avenues and highlight areas for future study that are likely to make these targets the focus of future treatments.
MeSH term(s)	Animals ; Autoimmune Diseases of the Nervous System/immunology ; Autoimmune Diseases of the Nervous System/pathology ; Autoimmune Diseases of the Nervous System/physiopathology ; Humans ; Immune Tolerance/physiology ; T-Lymphocytes, Regulatory ; Thymus Gland/immunology ; Thymus Gland/pathology
Language	English
Publishing date	2018-11-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2491514-2
ISSN	1759-4766 ; 1759-4758
ISSN (online)	1759-4766
ISSN	1759-4758
DOI	10.1038/s41582-018-0095-7
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Zs.MG 88: Show issues

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