ABSTRACT
The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.
Subject(s)
Antigens, Neoplasm , Neoplasms , Nerve Tissue Proteins , Paraneoplastic Syndromes, Nervous System , Animals , Humans , Mice , Autoantibodies , Capsid/metabolism , Epitopes , Neoplasms/complications , Paraneoplastic Syndromes, Nervous System/metabolism , Paraneoplastic Syndromes, Nervous System/pathology , Antigens, Neoplasm/metabolism , Nerve Tissue Proteins/metabolismABSTRACT
OBJECTIVE: Co-occurring anti-tripartite motif-containing protein 9 and 67 autoantibodies (TRIM9/67-IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67-IgG detection are not known. METHODS: We performed a retrospective, multicenter study to evaluate the cerebrospinal fluid and serum of candidate TRIM9/67-IgG cases by tissue-based immunofluorescence, peptide phage display immunoprecipitation sequencing, overexpression cell-based assay (CBA), and immunoblot. Cases in which TRIM9/67-IgG was detected by at least 2 assays were considered TRIM9/67-IgG positive. RESULTS: Among these cases (n = 13), CBA was the most sensitive (100%) and revealed that all cases had TRIM9 and TRIM67 autoantibodies. Of TRIM9/67-IgG cases with available clinical history, a subacute cerebellar syndrome was the most common presentation (n = 7/10), followed by encephalitis (n = 3/10). Of these 10 patients, 70% had comorbid cancer (7/10), 85% of whom (n = 6/7) had confirmed metastatic disease. All evaluable cancer biopsies expressed TRIM9 protein (n = 5/5), whose expression was elevated in the cancerous regions of the tissue in 4 of 5 cases. INTERPRETATION: TRIM9/67-IgG is a rare but likely high-risk paraneoplastic biomarker for which CBA appears to be the most sensitive diagnostic assay. ANN NEUROL 2023;94:1086-1101.
Subject(s)
Nerve Tissue Proteins , Paraneoplastic Cerebellar Degeneration , Humans , Retrospective Studies , Nerve Tissue Proteins/metabolism , Biomarkers/cerebrospinal fluid , Autoantibodies/cerebrospinal fluid , Immunoglobulin GABSTRACT
BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a poorly understood and heterogeneous manifestation of SLE. Common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes for NPSLE. A frequent end-result of major syndromes is neuronal or glial injury. Blood-based neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been utilized as markers for monitoring disease activity and/or severity in other neurodegenerative and neuroinflammatory diseases; however, they have not been evaluated in active major NPSLE. METHODS: This was a case-control study. We enrolled patients aged 12-60 years with active major NPSLE, SLE without active major NPSLE, and healthy controls. Active NPSLE was defined as being <6 months from last new or worsening neuropsychiatric symptom. Demographics, clinical data, and serum or plasma biosamples were collected. RESULTS: Thirteen patients with active major NPSLE, 13 age/sex/kidney function matched SLE controls without active major NPSLE, and 13 age/sex matched healthy controls (mean ages 26.8, 27.3, 26.6 years) were included. 92% of each group were female. Major syndromes included stroke (5), autonomic disorder (3), demyelinating disease (2), aseptic meningitis (2), sensorimotor polyneuropathy (2), cranial neuropathy (1), seizures (1), and myelopathy (2). Mean (standard deviation) blood NfL and GFAP were 3.6 pg/ml (2.0) and 50.4 pg/ml (15.0), respectively, for the healthy controls. Compared to healthy controls, SLE without active major NPSLE had mean blood NfL and GFAP levels 1.3 pg/ml (p = .42) and 1.2 pg/ml higher (p = .53), respectively. Blood NfL was on average 17.9 pg/ml higher (95% CI: 9.2, 34.5; p < .001) and blood GFAP was on average 3.2 pg/ml higher (95% CI: 1.9, 5.5; p < .001) for cases of active major NPSLE compared to SLE without active major NPSLE. In a subset of 6 patients sampled at multiple time points, blood NfL and GFAP decreased after immunotherapy. CONCLUSIONS: Blood NfL and GFAP levels are elevated in persons with SLE with active major NPSLE compared to disease matched controls and may lower after immunotherapy initiation. Larger and longitudinal studies are needed to ascertain their utility in a clinical setting.
ABSTRACT
Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to receive intrathecal stem cell injections as treatment for multiple sclerosis. We also review the management of this challenging central nervous system infection.
Subject(s)
Medical Tourism , Meningitis , Mycobacterium Infections, Nontuberculous , Mycobacterium abscessus , Humans , Meningitis/drug therapy , Mycobacterium abscessus/physiology , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/etiology , Mycobacterium Infections, Nontuberculous/drug therapy , Stem CellsABSTRACT
OBJECTIVES: To report the expanded neurological presentations and oncological associations of tripartite motif-containing protein 46 (TRIM46)-IgG seropositive patients. METHODS: Archived sera/cerebrospinal fluid (CSF) were evaluated by tissue-based immunofluorescence assay to identify patients with identical axon initial segment (AIS)-specific staining pattern. Phage immunoprecipitation sequencing (PhIP-Seq) was used to identify the putative autoantigen. RESULTS: IgG in serum (17) and/or CSF (16) from 25 patients yielded unique AIS-specific staining on murine central nervous system (CNS) tissue. An autoantibody specific for TRIM46 was identified by PhIP-Seq, and autoantigen specificity was confirmed by transfected COS7 cell-based assay. Clinical information was available for 22 TRIM46-IgG seropositive patients. Fifteen were female (68%). Median age was 67 years (range 25-87). Fifteen (68%) patients presented with subacute cerebellar syndrome (six isolated; nine with CNS accompaniments: encephalopathy (three), brainstem signs (two), myelopathy (two), parkinsonism (one)). Other phenotypes included limbic encephalitis (three), encephalopathy with/without seizures (two), myelopathy (two). Eighteen (82%) had cancer: neuroendocrine carcinomas (9; pancreatic (3), small-cell lung (4), oesophagus (1), endometrium (1)), adenocarcinomas (6; lung (2), ovarian (2), endometrial (1), breast (1)), sarcoma (2) and gastrointestinal tumour (1). Neurological symptoms in three followed immune checkpoint inhibitor (ICI) administration. CONCLUSIONS: This study supports TRIM46-IgG being a biomarker of paraneoplastic CNS disorders and expands the neurological phenotypes, oncological and ICI-related adverse event associations.
Subject(s)
Autoantibodies/cerebrospinal fluid , Nerve Tissue Proteins/cerebrospinal fluid , Paraneoplastic Syndromes, Nervous System/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Biomarkers/cerebrospinal fluid , Female , Humans , Limbic Encephalitis/cerebrospinal fluid , Male , Middle Aged , Retrospective StudiesABSTRACT
Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak.
Subject(s)
Encephalomyelitis , Exanthema , Mpox (monkeypox) , Sexual and Gender Minorities , Colorado/epidemiology , District of Columbia , Homosexuality, Male , Humans , Male , Mpox (monkeypox)/epidemiology , Monkeypox virus , United StatesABSTRACT
BACKGROUND: For patients with acute, serious neurological conditions presenting to the emergency department (ED), prognostication is typically based on clinical experience, scoring systems and patient co-morbidities. Because estimating a poor prognosis influences caregiver decisions to withdraw life-sustaining therapy, we investigated the consistency of prognostication across a spectrum of neurology physicians. METHODS: Five acute neurological presentations (2 with large hemispheric infarction; 1 with brainstem infarction, 1 with lobar hemorrhage, and 1 with hypoxic-ischemic encephalopathy) were selected for a department-wide prognostication simulation exercise. All had presented to our tertiary care hospital's ED, where a poor outcome was predicted by the ED neurology team within 24 hours of onset. Relevant clinical, laboratory and imaging data available before ED prognostication were presented on a web-based platform to 120 providers blinded to the actual outcome. The provider was requested to rank-order, from most to least likely, the predicted 90-day modified Rankin Scale (mRS) score. To determine the accuracy of individual outcome predictions we compared the patient's the actual 90-day mRS score to highest ranked predicted mRS score. Additionally, the group's "weighted" outcomes, accounting for the entire spectrum of mRS scores ranked by all respondents, were compared to the actual outcome for each case. Consistency was compared between pre-specified provider roles: neurology trainees versus faculty; non-vascular versus vascular faculty. RESULTS: Responses ranged from 106-110 per case. Individual predictions were highly variable, with predictions matching the actual mRS scores in as low as 2% of respondents in one case and 95% in another case. However, as a group, the weighted outcome matched the actual mRS score in 3 of 5 cases (60%). There was no significant difference between subgroups based on expertise (stroke/neurocritical care versus other) or experience (faculty versus trainee) in 4 of 5 cases. CONCLUSION: Acute neuro-prognostication is highly variable and often inaccurate among neurology providers. Significant differences are not attributable to experience or subspecialty expertise. The mean outcome prediction from group of providers ("the wisdom of the crowd") may be superior to that of individual providers.
Subject(s)
Emergencies , Nervous System Diseases , Acute Disease , Emergency Service, Hospital , Humans , Nervous System Diseases/therapy , Prognosis , Treatment OutcomeABSTRACT
Usutu virus is an emerging mosquito-borne flavivirus initially identified in South Africa in 1959 that is now circulating throughout parts of Africa, Europe, and the Middle East. It is closely related to West Nile virus, and has similar vectors, amplifying bird hosts, and epidemiology. Usutu virus infection can occur in humans and may be asymptomatic or cause systemic (e.g., fever, rash, and hepatitis) or neuroinvasive (e.g., meningitis and encephalitis) disease. Given few reported cases, the full clinical spectrum is not known. No anti-viral treatment is available, but it can be largely prevented by avoiding mosquito bites. Because of similar mosquitoes, birds, and climate to Europe, the potential for introduction to North America is possible.
Subject(s)
Flavivirus Infections/epidemiology , Flavivirus Infections/virology , Flavivirus , Animals , Flavivirus Infections/transmission , Humans , North AmericaABSTRACT
The clinical phenotype of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated proteinlike 2 (CASPR2) autoimmunity is well defined in adults. Data for children are limited (<10 cases). Among 13,319 pediatric patients serologically tested for autoimmune neurological disorders (2010-2017), 264 were seropositive for voltage-gated potassium channel-complex-IgG (radioimmunoprecipitation). Only 13 (4.9%) were positive by transfected cell-binding assay for LGI1-IgG (n = 7), CASPR2-IgG (n = 3), or both (n = 3). This is significantly less than in adults. Encephalopathy, seizures, and peripheral nerve hyperexcitability were common, as was coexisting autoimmunity. No faciobrachial dystonic seizures or cancers were identified. Functional neurologic disorders were frequently the initial diagnosis, and immunotherapy appeared beneficial. Ann Neurol 2018;84:473-480.
Subject(s)
Autoimmune Diseases of the Nervous System/immunology , Autoimmunity/immunology , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Proteins/metabolism , Adolescent , Autoantibodies/immunology , Autoantibodies/metabolism , Autoimmune Diseases of the Nervous System/metabolism , Child , Child, Preschool , Female , Humans , Immunotherapy/methods , Intracellular Signaling Peptides and Proteins , Male , Membrane Proteins/immunology , Nerve Tissue Proteins/immunology , Potassium Channels, Voltage-Gated/immunology , Proteins/immunologyABSTRACT
There are many arthropod-borne viruses (arboviruses) capable of neuroinvasion, with West Nile virus being one of the most well known. In this review, we highlight five rarer emerging or reemerging arboviruses capable of neuroinvasion: Cache Valley, eastern equine encephalitis, Jamestown Canyon, Powassan, and Usutu viruses. Cache Valley and Jamestown Canyon viruses likely circulate throughout most of North America, while eastern equine encephalitis and Powassan viruses typically circulate in the eastern half. Usutu virus is not currently circulating in North America, but has the potential to be introduced in the future given similar climate, vectors, and host species to Europe (where it has been circulating). Health care providers should contact their state or local health departments with any questions regarding arboviral disease surveillance, diagnosis, treatment, or prevention. To prevent neuroinvasive arboviral diseases, use of insect repellent and other mosquito and tick bite prevention strategies are key.
Subject(s)
Arbovirus Infections/epidemiology , Bunyaviridae Infections/epidemiology , Encephalitis, California/epidemiology , Encephalitis, Tick-Borne/epidemiology , Encephalomyelitis, Eastern Equine/epidemiology , Flavivirus Infections/epidemiology , Animals , Arbovirus Infections/diagnosis , Arbovirus Infections/therapy , Bunyamwera virus/isolation & purification , Bunyaviridae Infections/diagnosis , Bunyaviridae Infections/therapy , Encephalitis Virus, California/isolation & purification , Encephalitis, California/diagnosis , Encephalitis, California/therapy , Encephalitis, Tick-Borne/diagnosis , Encephalitis, Tick-Borne/therapy , Encephalomyelitis, Eastern Equine/diagnosis , Encephalomyelitis, Eastern Equine/therapy , Flavivirus/isolation & purification , Flavivirus Infections/diagnosis , Flavivirus Infections/therapy , HumansABSTRACT
When patients present with neurological syndromes, such as encephalopathy/encephalitis, meningitis, and/or myelopathy/myelitis, the differential diagnosis is often broad, including infectious, inflammatory, autoimmune, vascular, and neoplastic etiologies. Just with inflammatory and autoimmune etiologies alone, there are numerous causative diseases. A comprehensive history and physical examination investigating for extraneurologic manifestations of immune-mediated disease is often necessary. Moreover, evaluating for an underlying infection and/or immunodeficiency becomes a critical aspect to the workup. This article will focus on the association of viral infections and dysregulation of the immune system as triggers of autoimmunity, in addition to various systemic inflammatory diseases that can cause neurological disease either with or without an established rheumatological disorder.
Subject(s)
Autoimmune Diseases/immunology , Autoimmunity/immunology , Encephalitis/immunology , Meningitis/immunology , Nervous System Diseases/immunology , Autoimmune Diseases/complications , Encephalitis/complications , Humans , Infections/immunology , Meningitis/therapy , Nervous System Diseases/complications , Spinal Cord Diseases/complications , Spinal Cord Diseases/immunologyABSTRACT
The clinician who is evaluating a patient with a suspected central nervous system infection often faces a large differential diagnosis. There are several signs, symptoms, geographical clues, and diagnostic testing, such as cerebrospinal fluid abnormalities and magnetic resonance imaging abnormalities, which can be helpful in identifying the etiological agent. By taking a systematic approach, one can often identify life-threatening, common, and/or treatable etiologies. Here the authors describe some of the pearls and pitfalls in diagnosing and treating acute infectious meningitis and encephalitis.
Subject(s)
Encephalitis , Meningitis , Central Nervous System Infections , Diagnosis, Differential , Encephalitis/diagnosis , Encephalitis/therapy , Humans , Magnetic Resonance Imaging , Meningitis/diagnosis , Meningitis/therapyABSTRACT
Encephalitis has various etiologies, but viral infections and autoimmune disorders are the most commonly identified. Clinical signs, geographical clues, and diagnostic testing-including cerebrospinal fluid abnormalities and magnetic resonance imaging abnormalities-can be helpful in identifying the cause. Certain forms of encephalitis have specific treatments; hence, establishing a diagnosis rapidly and accurately is crucial. Here, we describe the clinical approach to diagnosing several common etiologies of encephalitis as well as treatment strategies.
Subject(s)
Encephalitis/diagnosis , Autoantibodies/immunology , Autoimmune Diseases/immunology , Encephalitis/drug therapy , Encephalitis/microbiology , HumansABSTRACT
Anti-NMDA receptor (NMDAR) encephalitis is characterized by a well-defined neuropsychiatric syndrome and CSF antibodies against the GluN1 subunit of the NMDAR. 40% of cases are related to underlying tumors, the vast majority ovarian teratomas (94%). We report a case of anti-NMDAR encephalitis associated with renal cell carcinoma (RCC). A 20-year-old female presented to the ED with behavioral changes, involuntary movements, tachycardia, and alternating obtundation with agitation which progressed over 3 weeks. Involuntary movements were severe, requiring intubation and sedation for control, and were accompanied by rhabdomyolysis. Brain MRI showed bilateral mesiotemporal T2/FLAIR hyperintensities. Anti-NMDAR antibodies were present in the serum (1:640) and CSF (1:320). Malignancy screening revealed a renal mass concerning for RCC, which was confirmed upon resection. She was started on high dose IV methylprednisolone and plasmapheresis, followed by rituximab. Lack of response led to escalating immunotherapy with cyclophosphamide. Clinical course was complicated by prolonged ICU admission, prolonged sedation, severe dysautonomia and bacteremia. Improvement began 2 months after immunotherapy, and she was discharged to rehabilitation 100 days after admission with mild neuropsychiatric symptoms. Repeat malignancy screenings, including whole-body imaging and transvaginal ultrasound were consistently negative. Herein, we describe a case of definite anti-NMDAR encephalitis in the setting of newly diagnosed RCC. This case illustrates how tumors other than ovarian teratomas may act as immunological triggers, as well as the complex and prolonged symptomatic and immunosuppressive therapies required in severe presentations of anti-NMDAR encephalitis.
ABSTRACT
BACKGROUND AND OBJECTIVES: To describe a case of glycine receptor (GlyR) antibody-positive stiff person syndrome (SPS) treated with autologous hematopoietic stem cell transplant (aHSCT). METHODS: This was a multicenter collaboration for the treatment of a single patient who underwent aHSCT as part of a clinical trial (NCT00716066). To objectively assess the response to transplantation, several clinical outcome measures were evaluated pretransplant and up to 18 months post-transplant, including modified Rankin Score (mRS), stiffness index, Hauser Ambulation Score (HAS), hypersensitivity index, timed 25-foot walk, and Montreal Cognitive Assessment. RESULTS: After transplant, the patient achieved sustained clinical improvement evidenced across various clinical scales, including mRS, stiffness index, HAS, and 25-foot walk time. DISCUSSION: aHSCT represents a promising treatment option for SPS, including for GlyR-positive patients. In addition, this case represents the need to validate and standardize best clinical outcome measures for patients with SPS. CLASSIFICATION OF EVIDENCE: Class IV; this is a single observational study without controls.
Subject(s)
Hematopoietic Stem Cell Transplantation , Stiff-Person Syndrome , Humans , Receptors, Glycine , Stiff-Person Syndrome/therapy , Transplantation, Autologous , Multicenter Studies as Topic , Clinical Trials as TopicABSTRACT
BACKGROUND: The ability to recognize and address bias is an important communication skill not typically addressed during training. We describe the design of an educational curriculum that aims to identify and change behavior related to diversity, equity, and inclusion (DEI). "DEI at the Bedside" uses the existing infrastructure of bedside teaching and provides a tool to normalize DEI discussions and develop skills to address bias during a neurology inpatient rotation. METHODS: As part of traditional clinical rounds, team members on an inpatient service shared experiences with DEI topics, including bias. The team developed potential responses should they encounter a similar situation in the future. We report the results of our needs assessment and curriculum development to evaluate the feasibility of incorporating a DEI educational curriculum in the neurology inpatient setting. RESULTS: Forty-two DEI experiences were recorded. Medical students were the most frequent discussants (44%). Direction of bias occurred between healthcare team members (33%), against patients (31%), and patients against healthcare team members (28%). Experiences ranged from microaggressions to explicit comments of racism, sexism, and homophobia. CONCLUSIONS: Based on needs assessment data, we developed a DEI educational curriculum for the inpatient neurology setting aimed to improve knowledge and skills related to DEI topics as well as to normalize conversation of DEI in the clinical setting. Additional study will demonstrate whether this initiative translates into measurable and sustained improvement in knowledge of how bias and disparity show up in the clinical setting and behavioral intent to discuss and address them.
Subject(s)
Education, Medical , Neurology , Humans , Diversity, Equity, Inclusion , Inpatients , CommunicationABSTRACT
OBJECTIVES: (1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity. METHODS: Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed-effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. RESULTS: The primary vaccination induced an 11- to 208-fold increase in binding and neutralizing antibody levels and a 3- to 4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3- to 5-fold increase in binding antibodies and 4- to 5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity. INTERPRETATION: Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered.
Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 Vaccines , COVID-19 , Multiple Sclerosis , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/prevention & control , Male , Female , Middle Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/administration & dosage , Adult , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Longitudinal Studies , SARS-CoV-2/immunology , Multiple Sclerosis/immunology , Multiple Sclerosis/drug therapy , Antibodies, Viral/blood , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Immunity, Cellular/drug effects , Vaccination , Immunity, Humoral/drug effects , Immunity, Humoral/immunology , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/immunologyABSTRACT
The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.
Subject(s)
COVID-19 , Multiple Sclerosis , Humans , COVID-19 Vaccines , RNA, Viral , COVID-19/prevention & control , SARS-CoV-2 , RNA, MessengerABSTRACT
Cerebrospinal fluid (CSF) eosinophilia is associated with a narrow differential, primarily including parasitic and fungal infections, neoplasm, and chemical meningitis. It has rarely been reported in neuroinflammatory conditions including as a finding of CSF cytology in two autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy cases. Here we describe a case of autoimmune GFAP astrocytopathy with classic clinical and radiographic features as well as presence of eosinophils in the CSF. This case highlights a potential association of eosinophils in the CSF with autoimmune GFAP astrocytopathy, which may suggest its inclusion in the differential diagnosis of eosinophilic meningitis, encephalitis, or myelitis.
Subject(s)
Autoimmune Diseases of the Nervous System , Encephalitis , Meningitis , Humans , Glial Fibrillary Acidic Protein , Eosinophils , Encephalitis/cerebrospinal fluid , Meningitis/diagnostic imaging , Astrocytes/metabolism , AutoantibodiesABSTRACT
Cognitive dysfunction (CD) is a neurologic complication of pediatric systemic lupus erythematosus (SLE) that remains poorly understood and understudied, despite the potential negative effects of CD on long-term socioeconomic status and quality of life. Data regarding the prevalence and risk factors for CD in pediatric SLE as well as the optimal screening, treatment, and long-term outcomes for CD are lacking. In this review, we present current knowledge on CD in pediatric SLE with a focus on the application to clinical practice. We discuss the challenges in diagnosis, clinical screening methods, potential impacts, and interventions for this complication. Finally, we discuss the remaining gaps in our knowledge of CD in pediatric SLE, and avenues for future research efforts.