Low Antibody Titers Research Articles

Antibody response to SARS-CoV2 before and after the third vaccination in patients with Inflammatory Bowel Disease.

Introduction Patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapy might have an increased risk of developing a severe course of SARS-CoV-2 infection. The aim of this study was to investigate the development of antibodies in immunosuppressed patients with IBD compared to a healthy control group and to determine the effect of immunmodulators on the level of anti-SARS-CoV-2 IgG antibody levels before and after a third vaccination against SARS-CoV-2. Methods This is a single-center study with a retrospective observational design. Seventy-one IBD patients matched by propensity score to 71 healthy employees (control group) were included. Blood was taken from both groups at predetermined times before and after the third booster vaccination. Results All patients with IBD (n=71, 100%) received immunomodulatory therapy. The mean antibody level before the third vaccination was 1352.88 U/ml (SD= 1011.489) in the IBD group and were not lower compared to the control group (p= 0.088). Gender, age, and disease duration had no significant impact on the development of antibody levels. Patients with TNF-alpha blockers had significantly lower antibody titers (p=0.011) compared to the control group. Patients with integrin inhibitor therapy had significantly higher antibody titers (p=0.003) than the controls. After the third vaccination, an increase in antibody titers was recorded in all patients in the IBD group. Conclusion We recorded an antibody titer in all patients with IBD that was not significantly lower compared to healthy controls despite immunomodulatory therapy. The booster vaccination led to an increase in antibody levels in all patients with IBD.

Experimental in vivo models for understanding inter-molecular interactions and preventing multifactor disease development

The increased spontaneous fragility in the centromere regions of the chromosomes predisposes to abnormal cellular division due to abnormal interaction with the mitotic spindle, which leads to number chromosomal aberrations. The abnormal structure of the microtubule-associated proteins (MAPs) could also be among the internal factors, predisposing to these pathologies. On the other hand, the increased frequency of the spontaneous chromosomal fragility suggests abnormal structure of the respective chromosomal/chromatin components and thus an increased risk about gene mutations and structural chromosomal aberrations. The spontaneous chromosomal fragility was tested by light microscopy observation of metaphases from peripheral blood lymphocytes of 8 patients with polygene pathologies (neoplasms, neuro-degenerative diseases, and neuro-psychiatric disorders) and of 18 healthy controls. In the tested patients was established significantly higher frequency of the spontaneous chromosomal fragility, including in the centromere chromosomal regions, compared to the controls. Different inter-molecular interactions, which could prevent the pathology appearance, were investigated by appropriate experimental in vivo models. As a whole, in the most cases, the presented data showed significantly lower average titers of anti-ganglioside antibodies and gangliosides in the samples from myocardium and liver than in the samples from brain and pancreas. By taking into consideration that the myocardium and liver are known as the most enriched of GSH anatomic organs, the presented data could be explained with the literature messages of higher amounts of de novo-synthesized free GSH tri-peptide in the same two organs. Moreover, a possibility about the production of antibodies/immunoglobulins by non-lymphoid types of cells, tissues, and organs in appropriate conditions was shown. Because the so-produced antibodies are out of the germinative centers in the specialized lymphoid tissues and organs, the control of their functions by small ions and molecules as gangliosides is very important. In the current study, the attention was particularly directed to the iteractions with the participation of gangliosides, the reduced form of the tri-peptide glutathione (GSH), and the protein HACE1. Besides the tumor-suppressor activity of protein HACE1, also its neuroprotective influence was proven, namely by interactions with specific molecules.

Assessing humoral immunity in daily practice: A retrospective study in a pediatric tertiary center

The evaluation of humoral immunity is usually performed through the assessment of serum immunoglobulin levels, vaccine titer responses, and B-cell enumeration and phenotyping. We performed a retrospective study assessing humoral immunity in 469 pediatric patients referred at the Sainte-Justine University Hospital Center. Almost half of the patients had at least one abnormal humoral immunological parameter at their evaluation, with low vaccine response titer to protein antigen being the most frequent. Fifteen patients (3.2 %) had a proven monogenic IEI, and 21 patients (4.5 %) required Ig replacement. Besides the infectious burden, hypoIgG remains the only parameter associated with Ig replacement therapy after the age of 6 years. Low antibody titers against conjugate vaccines had low sensitivity and positive predictive values for starting Ig replacement. Our study highlights the challenge of evaluating the humoral function in the pediatric population with suspected IEI with significant age and sex-dependent variability between parameters.

HLA-B*15 Is Associated With SARS-CoV-2 Infection in a Brazilian Population.

Studies have suggested an association between polymorphisms in class I genes of the major histocompatibility complex, specifically the human leukocyte antigen (HLA), and susceptibility to SARS-CoV-2. To explore this, 135 individuals with positive serological tests for SARS-CoV-2 were recruited. All the samples were collected before the advent of vaccines, avoiding immunization effects. Participants were divided into high and low neutralizing antibody titer groups, and polymorphisms in HLA-A, HLA-B, and HLA-DRB1 genes were examined using PCR-SSO. Allele prevalence in the study population was compared to the National Bone Marrow Volunteer Donors Register (REDOME) in São Paulo and between the high and low titer groups within the study population. Results indicated that the HLA-B*15 polymorphism was more prevalent in the COVID-19 positive group compared to the control population (COVID-19 = 0.1370; Control = 0.0875; p = 0.0067). The HLA-B*18 polymorphism was less prevalent in the COVID-19 group (COVID-19 = 0.0185; Control = 0.0534; p = 0.0064). Additionally, the HLA-A*30 polymorphism was more prevalent in the high titer group within the (high = 0.10937; low = 0.02816; p = 0.0125). Other polymorphisms showed no significant differences. These findings align with international studies, suggesting these genes plays a role in COVID-19 pathophysiology, however, further research is required to fully understand their impact.

Comparison of Three Different IBD Vaccination Protocols in Broiler Chicken-Efficacy, Serological Baselines and Histo-Pathological Lesions in the Bursa of Fabricius.

Infectious bursal disease (IBD) is a highly infectious disease of chicken found in all latitudes, due to the very high resistance to environmental conditions and commonly used disinfectants of the IBD virus (IBDV). This study was conducted to evaluate three IBD vaccination protocols in broiler chicken in terms of their effectiveness (clinical observations and production performance of the flock), estimation of serological baseline values (with the use of two different commercial ELISA kits) and the degree of progression of BF lesions (histopathological lesion score (HLS)) after vaccination. The three protocols were (I) single vaccination using an intermediate plus vaccine, (II) double vaccination with an intermediate vaccine and (III) double vaccination with an intermediate plus vaccine. Birds on farms vaccinated with protocol II were characterized by the lowest antibody titers in both ELISA tests and the lowest average HLS. The highest IDEXX titers were obtained in birds vaccinated with protocol III, while in the BIOCHEK test the highest titers were obtained for birds vaccinated with protocol I. Protocols I and III were characterized by similar HLSs. Birds vaccinated with protocols I and III had higher immune uniformity. The estimated serological baseline values and the degree of HLSs presents a clear picture of the differences between the different vaccination protocols and allows their adaptation for different farms depending on the current IBD epidemiological situation.

Analysis of Pregnancy Outcomes in Patients Exhibiting Recurrent Miscarriage With Concurrent Low-Titer Antiphospholipid Antibodies.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal-fetal complications in patients with low-titer aPLs. The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (n = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (n = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal-fetal complications were subsequently compared. The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (p < 0.05) and a higher ANA positivity rate (p < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (p < 0.05). Post treatment, the live birth rate in the low-titer group significantly exceeded that of the untreated group (67.6%vs. 33.3%; p = 0.005). The miscarriage rate was notably lower in untreated low-titer patients compared to aPLs-negative patients (32.4%vs. 66.7%; p = 0.005). No significant differences were observed in maternal or fetal complications between the groups. In the standard treatment group (Group A), there were 8 (53.3%) live births, whereas the multidrug treatment group (Group B) had 40 (71.4%) live births, a significantly higher rate than in the standard treatment group, although the difference lacked statistical significance. The study indicates that untreated RM patients with low-titer positive aPLs have a higher recurrence of miscarriage compared to the aPLs-negative RM group. However, recurrence significantly decreases following appropriate intervention, suggesting the benefits of treatment for RM patients with low-titer aPLs.

7217 Impact of INZ-701 on Bone and Mineral Metabolism Biomarkers and Clinical Outcomes in Adults with ENPP1 Deficiency - Results from 48-week Phase 1/2 Open Label Study

Abstract Disclosure: K. Gunter: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. R.A. Wermers: Research Investigator; Self; Inozyme Pharma. R. Fuhr: Employee; Self; Parexel GmbH. Research Investigator; Self; Inozyme Pharma. D. Schnabel: Research Investigator; Self; Inozyme Pharma. A. Besancon: Research Investigator; Self; Inozyme Pharma. M.A. Nour: Research Investigator; Self; Inozyme Pharma. D. Wenkert: Stock Owner; Self; Inozyme Pharma. Y. Sabbagh: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. Background: ENPP1 Deficiency is a rare disorder due to inactivating mutations in the ENPP1 gene that result in low levels of inorganic pyrophosphate (PPi), a critical regulator of mineralization. Subsequent pathologic soft tissue calcification results in severe vascular calcification and ∼50% infant mortality. By early adolescence the majority of survivors develop FGF-23 mediated hypophosphatemic rickets, characterized by bone deformities, short stature, joint/ligament calcification and musculoskeletal pain. No targeted therapy exists for this disease. INZ-701 is a recombinant ENPP1-Fc investigational product. Purpose: To describe the safety, tolerability, immunogenicity, and exploratory efficacy (bone and mineral metabolism biomarkers and clinical outcomes) of INZ-701 in adults with ENPP1 Deficiency through the end of the phase 2 study period (week 48). Methods: Phase 1/2, multicenter, open-label, multiple ascending dose study including three adults in each of three dose cohorts (0.2, 0.6 and 1.8 mg/kg, total N=9) with genetic variants in ENPP1 and PPi &amp;lt;1300 nM (NCT04686175). Participants were dosed subcutaneously on Day 1, then twice weekly from Day 8 to end of study. Data through wk 48 as of July 6, 2023 are included; topline wk 48 data will be presented. Per protocol, participants may continue to receive INZ-701 beyond wk 48. Results: Rapid increase in mean PPi from baseline of 426±407 nM was noted in all patients, reaching the healthy volunteer range within 6 hrs of the first dose with sustained elevation through wk 48. Mean PPi across the 0.2, 0.6 and 1.8 mg/kg dose cohorts from day 32 to wk 48 was 1299±131 nM, 1356±136 nM, and 1282±81 nM, respectively. There were improvements from baseline to wk 48 in mean pooled FGF-23 (-22 pg/mL) and serum phosphate (+0.18 mg/dL), with dose-dependent changes in bone specific alkaline phosphatase consistent with bone healing. DEXA revealed improvements in spine BMD and BMC. There were trends towards improvement in mean % predicted change in 6MWT from baseline to wk 48: cohort 1, 76.7% (SE 10.5) to 85.0% (SE 3.0); cohort 2, 52.2% (SE 10.9 ) to 79.0% (SE 2.9); cohort 3, wk 48 data not available. Improvements were also observed in physician and patient global impression of change score (with no patients deteriorating) and PROMIS pain intensity score. INZ-701 was well tolerated with no drug-related serious or severe (&amp;gt; grade 2) adverse events. Low titers of non-neutralizing anti-drug antibodies (≤160) were observed in 7/9 patients. Long half-life of approximately 126 hours suggests the potential for once-weekly dosing. Conclusions: In adults with ENPP1 Deficiency, INZ-701 was well tolerated with no related serious or severe adverse events. INZ-701 demonstrated a rapid and sustained increase in PPi levels from baseline to week 48 with corresponding improvements in bone mineral biomarkers, functional performance, and patient and physician-reported outcomes. Presentation: 6/3/2024

Assessment of post-COVID-19 vaccination neutralizing antibodies in kidney transplant and hemodialysis patients versus the general population

Background Patients receiving hemodialysis (HD) and kidney transplant recipients are immunocompromised populations prioritized for coronavirus disease 2019 (COVID-19) vaccination, however, there were few clinical trials with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine responses. Compared with controls, individuals with chronic kidney disease and those on immunosuppressants have lower antibody titers and rates of seroconversion after vaccination. There is a lack of data on their humoral response to COVID-19 immunization. To study the effect of different types of available COVID-19 vaccines in Egypt (AstraZeneca, Sinopharm, Pfizer/BioNTech, and Sputnik) on neutralizing antibodies against COVID-19 in HD and kidney transplantation patients compared with the healthy population. Patients and methods A total of 84 participants; 28 HD patients, 28 kidney transplant recipients, and 28 healthy medical staff members were recruited to test the serological reaction. Six months following the second dose of the COVID-19 vaccine, we evaluated antibody titers against SARS-CoV-2 by Elecsys Anti-SARS-CoV-2 S (Roch) and collected data from the patients, including their comorbidities and the length of time since their kidney transplant. Results All the study groups were comparable as regards age, sex, and BMI, however, hemoglobin was significantly higher in the control group. Antibody response to vaccination was strongest in the control group (100%), followed by HD patients (85%), with transplant recipients showing a significantly weaker response (60%). The Pfizer vaccine generated higher neutralizing antibody levels compared with other vaccines in this study. Yet, the difference was not statistically significant. Additionally, no significant difference in response between the different vaccine types. the transplant group displayed significantly lower levels compared with the control group (P&lt;0.001) and a trend towards lower levels compared with the dialysis group (P=0.06). Conclusion Our study found that all tested vaccines generated comparable levels of neutralizing antibodies in healthy individuals and those with chronic kidney disease (dialysis patients). While 85% of dialysis patients achieved seroconversion (positive antibody test) similar to the healthy control group, only 60% of kidney transplant recipients did. the duration post-transplant may be associated with higher rate of seroconversion. the transplant group displayed lower levels of antibodies compared with the control and the dialysis group which suggests a weaker immune response in transplant patients.

Isolation and genetic characterization of canine adenovirus type 2 variant from raccoon dog (Nyctereutes procynoide koresis) in Republic of Korea

Canine adenovirus type 2 (CAV-2) is a common causative agent of respiratory disease in canines. There have been no reports of CAV-2 variants isolated from raccoon dogs. This study aims to investigate the biological and genetic characteristics of a novel Korean CAV-2 variant. Madin-Darby canine kidney cells were used to isolate the CAV-2 variant from 45 fecal swab samples. Diagnostic tools such as the cytopathic effect (CPE) assay, electron microscopy, polymerase chain reaction, and immunofluorescence and hemagglutination assays were used to confirm the presence of the CAV-2 isolate. A cross-virus neutralization assay was performed to verify the novelty of this CAV variant. Genetic analysis was performed using nucleotide sequences obtained through next-generation sequencing. The isolate was confirmed to be a CAV-2 variant based on the aforementioned methods and designated CAV2232. The number of bases in the fiber and E3 genes of CAV2232 were 1,626 and 414, respectively. Phylogenetic analysis of the fiber and E3 genes confirmed that CAV2232 was classified into a different clade from the known CAV-1 and CAV-2 strains. Mice inoculated with the CAV2232 vaccine developed high virus neutralization antibody titers of 1,024 (210) against CAV2232, while mice inoculated with CAV-1 and CAV-2 vaccines had low virus neutralization antibody titers of 12.9 (23.7) and 6.5 (22.7), respectively, against CAV2232. CAV2232 isolated from wild raccoon dog feces was classified as a novel CAV-2 variant. CAV2232 may therefore be used as an antigen for new vaccine development and serological investigations.

Clinical characteristics and therapeutic effect of myasthenia gravis coexisting with thyroid eye disease.

Here, we describe the clinical characteristics and therapeutic effects of myasthenia gravis (MG) coexisting with thyroid eye disease (TED). We collated clinical data from MG patients in our hospital between 2012 and 2022 and analyzed the clinical characteristics of MG patients with hyperthyroidism, MG patients with TED and ocular myasthenia gravis (OMG) patients with TED. We recruited 62 MG patients with hyperthyroidism, including 13 MG patients with TED and 10 OMG patients with TED. There were 70 MG patients without hyperthyroidism; 29 of these were OMG. Compared with patients without hyperthyroidism, patients with hyperthyroidism had an earlier age at onset and milder clinical symptoms (P < 0.05). The incidence of thymus hyperplasia in patients with hyperthyroidism and TED was significantly lower than that in patients without TED (38.5% vs. 69.4%, P < 0.05); these patients also had a significantly lower antibody titer for the acetylcholine receptor [0.72 (0.27, 14.93) nmol/L vs. 2.38 (0.28, 49.51) nmol/L, P < 0.05]. Diplopia was significantly more frequent in OMG patients with TED than in patients with OMG (84.6% vs. 44.8%, P < 0.05), and the rate of diplopia in OMG patients with TED was significantly higher after treatment with bromostigmine and glucocorticoid (69.2% vs. 3.4%, P < 0.05). MG patients with TED had a significantly lower incidence of thymus hyperplasia and a lower antibody titer for the acetylcholine receptor. Patients with OMG and TED are more likely to develop diplopia; it is very difficult to treat diplopia in these patients.

Delayed peak antibody titers after the second dose of SARS-CoV-2 vaccine in solid organ transplant recipients: Prospective cohort study

Poor post-vaccination production of antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a concern among solid organ transplant (SOT) recipients. Furthermore, the timing and kinetics of antibody titers after the second vaccine dose are unknown. We conducted a multicenter prospective observational study that included 614 SOT recipients: 460 kidney, 53 heart, 50 liver, 20 lung, and 31 simultaneous pancreas–kidney (SPK). The participants received two doses of the mRNA vaccine (Pfizer BNT162b2 or Moderna mRNA-1273), as indicated. Serum samples were collected before the first and second vaccinations and at 1, 3, and 6 months after the second vaccine dose, which were then assessed for SARS-CoV-2 antibodies. The overall seropositivity rate was 43% at 1 month after administration of the second vaccine dose; it gradually increased to 68% at 3 months after second dose administration and to 70% at 6 months. In addition, recipient of kidney, lung or SPK transplants had lower antibody titers at the 3- and 6-month time points than did the other recipients. SOT recipients acquired SARS-CoV-2 S-IgG antibodies slowly, and the peak titer differed significantly from that of the general population.

Stiff Person Syndrome and GAD Antibody-Spectrum Disorders.

Antibodies against glutamic acid decarboxylase (GAD), originally associated with stiff person syndrome (SPS), define the GAD antibody-spectrum disorders that also include cerebellar ataxia, autoimmune epilepsy, limbic encephalitis, progressive encephalomyelitis with rigidity and myoclonus (PERM), and eye movement disorders, all of which are characterized by autoimmune neuronal excitability. This article elaborates on the diagnostic criteria for SPS and SPS spectrum disorders, highlights disease mimics and misdiagnoses, describes the electrophysiologic mechanisms and underlying autoimmunity of stiffness and spasms, and provides a step-by-step therapeutic scheme. Very-high serum GAD antibody titers are diagnostic for GAD antibody-spectrum disorders and also predict the presence of GAD antibodies in the CSF, increased intrathecal synthesis, and reduced CSF γ-aminobutyric acid (GABA) levels. Low serum GAD antibody titers or the absence of antibodies generates diagnostic challenges that require careful distinction in patients with a variety of painful spasms and stiffness, including functional neurologic disorders. Antibodies against glycine receptors, first found in patients with PERM, are seen in 13% to 15% of patients with SPS, whereas amphiphysin and gephyrin antibodies, seen in 5% of patients with SPS spectrum disorders, predict a paraneoplastic association. GAD-IgG from different SPS spectrum disorders recognizes the same dominant GAD intracellular epitope and, although the pathogenicity is unclear, is an excellent diagnostic marker. The biological basis of muscle stiffness and spasms is related to autoimmune neuronal hyperexcitability caused by impaired reciprocal γ-aminobutyric acid-mediated (GABA-ergic) inhibition, which explains the therapeutic response to GABA-enhancing agents and immunotherapies. It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses, considering that SPS is treatable if managed correctly from the outset to prevent disease progression. A step-by-step, combination therapy of GABA-enhancing medications along with immunotherapies ensures prolonged clinical benefits.

A Pseudovirus Nanoparticle Displaying the Vaccinia Virus L1 Protein Elicited High Neutralizing Antibody Titers and Provided Complete Protection to Mice against Mortality Caused by a Vaccinia Virus Challenge.

The recent worldwide incidence of mpox infection and concerns about future emerging variants of mpox viruses highlight the need for the development of a new generation of mpox vaccines. To achieve this goal, we utilized our norovirus S nanoparticle vaccine platform to produce and evaluate two pseudovirus nanoparticles (PVNPs), S-L1 and S-J1. These PVNPs displayed the L1 neutralizing antigen target of the vaccinia virus and a yet-untested J1 antigen of the mpox virus, respectively, with the aim of creating an effective nanoparticle-based mpox vaccine. Each self-assembled PVNP consists of an inner shell resembling the interior layer of the norovirus capsid and multiple L1 or J1 antigens on the surface. The PVNPs improved the antibody responses toward the displayed L1 or J1 antigens in mice, resulting in significantly greater L1/J1-specific IgG and IgA titers than those elicited by the corresponding free L1 or J1 antigens. After immunization with the S-L1 PVNPs, the mouse sera exhibited high neutralizing antibody titers against the vaccinia virus, and the S-L1 PVNPs provided mice with 100% protection against mortality caused by vaccinia virus challenge. In contrast, the S-J1 PVNPs induced low neutralizing antibody titers and conferred mice weak protective immunity. These data confirm that the L1 protein is an excellent vaccine target and that the readily available S-L1 PVNPs are a promising mpox vaccine candidate worthy of further development.

Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis

BackgroundIsolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE. MethodsThis multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data was performed. ResultsOf 249 children included, 12 (5%) had only psychiatric symptoms without other typical clinical features of autoimmune encephalitis at presentation. All but one (11 of 12 = 92%) had at least one abnormal finding on initial ancillary testing: eight of 12 (67%) had an abnormal EEG, six of 12 (50%) had an abnormal MRI, and five of 12 (42%) demonstrated CSF pleocytosis. The single patient with a normal MRI, EEG, and CSF profile had low positive CSF NMDA antibody (titer of 1:1), and symptoms improved without immunotherapy. ConclusionsIsolated first-episode psychiatric symptoms in pNMDARE are uncommon, and the majority of children will exhibit additional neurodiagnostic abnormalities. Delaying immunotherapy in a child with isolated psychiatric symptoms and normal neurodiagnostic testing may be warranted while awaiting confirmatory antibody testing.

Sustained chronic inflammation and altered childhood vaccine responses in children exposed to Zika virus

Congenital Zika virus (ZIKV) infection leads to severe newborn abnormalities, but its long-term impact on childhood immunity is not well understood. This study aims to investigate the serum proteomics in children exposed to ZIKV during pregnancy to understand potential immunological consequences during early childhood. The study included ZIKV-exposed infants (ZEI) at birth (n=42) and children exposed to ZIKV (ZEC) at two years of age (n=20) exposed to ZIKV during pregnancy, as well as healthy controls. Serum proteomic analysis was performed on these groups to assess inflammation and immune profiles. Additionally, antibody titres against two common childhood vaccines, DTaP and MMR, were measured in healthy controls (n=50) and ZEC (n=92) to evaluate vaccine-induced immunity. Results showed elevated inflammation in ZEI with birth abnormalities. Among ZEC, despite most having normal clinical outcomes at two years, their serum proteomics indicated a bias towards Th1-mediated immune responses. Notably, ZEC displayed reduced anti-Diphtheria toxin and anti-Clostridium tetani IgG levels against DTaP and MMR vaccines. They also exhibited lower antibody titres particularly against Th2-biased DTaP vaccines, but not Th1-biased MMR vaccines. In conclusion, the study highlights the long-term immunological consequences of congenital ZIKV exposure. Heightened inflammation was observed in ZEI with abnormalities at birth, while ZEC maintained a chronic Th1-biased immune profile. The impaired response to Th2-biased vaccines raises concerns about lasting effects of ZIKV exposure on immune responses. Consequently, there is a need for continued longitudinal clinical monitoring to identify potential immune-related complications arising from prenatal exposure to ZIKV. This work was partially funded by the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Dental and Craniofacial Research (NIDCR).

Neutralizing Antibodies Targeting BK Polyomavirus: Clinical Importance and Therapeutic Potential for Kidney Transplant Recipients.

Most of the world's adult population is latently infected by the BK polyomavirus. It causes asymptomatic infection in healthy individuals but emerged as a threat to kidney transplant recipients because of virus-associated nephropathy caused by immunosuppressive therapy. In these conditions, when a functional cellular response is impaired by immunosuppression, neutralizing antibodies may play a major role because they can directly prevent infection of target cells, independently of cell-mediated immunity, by binding to the viral particles. Studying the contribution of anti-BK virus neutralizing antibodies in viral control has long been hampered by the lack of convenient in vitro models, but major progress has been made in the past decade. The four BK virus genotypes have been demonstrated to behave as distinct serotypes. A low recipient neutralizing antibody titer against the donor's serotype before kidney transplant has been significantly associated with BK virus replication after transplant. Different mechanisms exploited by the BK virus to evade neutralizing antibodies have been described. Recent studies also support the potential benefit of administering intravenous Igs or monoclonal neutralizing antibodies as a therapeutic strategy, and more interestingly, this could also be used as preventive or preemptive therapy before advanced kidney damage has occurred. Besides, neutralizing antibodies could be induced by vaccination. In this review, we summarize accumulated knowledge on anti-BK virus neutralizing antibodies as well as their clinical importance and therapeutic potential for kidney transplant recipients.

Immunogenicity of the Inactivated SARS-CoV-2 Vaccine (BBIBPCorV) in Hemodialysis Patients: A Case-Control Study

Background: Studies have shown that immune responses to COVID-19 vaccines are impaired in dialysis patients, which may affect their immunity to vaccines. Therefore, this study aimed to evaluate SARS-COV-2 neutralizing antibodies in hemodialysis patients for 2 and 6 weeks after receiving inactivated Sinopharm vaccine. Method: In this study, 172 people were divided into two groups. The first group included 108 hemodialysis patients, while the second group included 64 health workers as a control group. To evaluate SARS-COV-2 neutralizing antibody titers, peripheral blood samples were collected from all participants 2 and 6 weeks after receiving the second dose of the Sinopharm vaccine. Samples were centrifuged, and the neutralizing antibody against the receptor-binding domain (RBD) was determined using the indirect ELISA technique. Results: Hemodialysis patients had lower IgG-neutralizing antibody titers than the control group (P &lt;0.001). The titers of SARS-COV-2 neutralizing antibodies were not significantly different at two weeks compared to six weeks after vaccination (P=0.9204). Our findings showed a significant increase in titers of IgGneutralizing antibodies after vaccination in people with a history of COVID-19 (P=0.002). The seropositivity rate for neutralizing antibodies against RBD was significantly different between seropositive (immune) and seronegative (non-immune) patients six weeks after vaccination (P=0.022). Conclusion: The titers of neutralizing antibodies against SARS-COV-2 were lower in hemodialysis patients than in healthy individuals. This is probably due to the poor immune system. However, patients who received two doses of inactivated Sinopharm vaccine showed a higher antibody titer six weeks after vaccination.

Dynamics of Antibody Response to Covishield Vaccine after 6 Months: A Longitudinal Prospective Study.

To study the dynamics of antibody responses in the real world up to 6 months following two Covishield vaccination doses and evaluate its correlation with age. From March 2021 to February 2022, a prospective, longitudinal study of healthcare workers (HCWs) from a dedicated COVID-19 hospital was conducted. Institutional Ethics Committee permission was obtained. HCWs were divided into two groups. The first group consisted of individuals who had received the first dose of the COVID-19 vaccine, with at least 3 weeks elapsed since the dose, and who had not received the second dose until the initial blood sample for antibody testing was obtained. The second group consisted of individuals who had received both COVID-19 doses and had at least 2 weeks between the administration of the second dose and the collection of the first sample for antibody testing. In March 2021, after undergoing phlebotomy for serum collection, the participants responded to the survey. Electrochemiluminescence immunoassay (ECLIA) was used to perform a quantitative test for antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein receptor domain [receptor binding domain (RBD)]. The test used had a 98.8% sensitivity and a 99.9% specificity. If the antibody titer was 0.80 U/mL or higher, it was deemed positive; if it was lower, it was deemed negative. Two follow-ups were conducted for both groups, 3 and 6 months following the first sample collection. During both follow-up visits, a blood sample was obtained for testing the amount of antibody response, and the history of COVID-19 disease following the initial sample was taken. Every HCW had received the Covishield vaccination. After the vaccine's first dosage, 61 HCWs in the first group underwent antibody testing. The information about the 43 HCWs in the first group who attended the two follow-ups is as follows. There were 14 (32.6%) nurses and 5 (11.6%) doctors among the 43 HCWs. The age range was 21-55 years, with the median [interquartile range (IQR)] age being 26 (22-40) years and 20 (60.5%) being females. The vaccination series had a median (IQR) of 34 (29-49) days between doses. There was a statistically significant difference in immunoglobulin G (IgG) levels of the three samples, χ2 = 13.579, p = 0.001. Median (IQR) IgG levels of the three samples at 1 month after the first dose, 3 and 6 months after the second dose were 8511 (51-15400) U/mL, 1471 (249-5050) U/mL, and 978 (220-2854) U/mL, respectively. The antibody titer was negative for two HCWs in the first sample, positive in the rest of the samples, and positive in all samples in both follow-ups. In the second group, following two COVID-19 dosages, a total of 65 HCWs had tested positive for antibodies. The information of the 56 HCWs in group II who attended both follow-ups is as follows. Of the 56 HCWs, 15 (26.8%) were doctors, 27 (48.2%) were nurses, and 14 (25%) were others. The age range was 20-64 years, with a median (IQR) of 29.5 (22-37.7) and 31 (55.3%) female participants. The vaccination series had a median (IQR) interval of 32 (29-35) days between doses. There was a statistically significant difference in IgG levels of the three samples, χ2 = 31.107, p < 0.0001. Median (IQR) IgG levels of the three samples at 20 days, 3.8 months, and 7 months after the second dose were 2377.5, 1345.5, and 1257 U/mL, respectively. Spearman's rank order correlation was used to assess the association between IgG level and age in both groups. The relationship between IgG levels and age was weakly correlated and not statistically significant. There is a waning of antibody titer over time postimmunization. A lower antibody titer can be a contributing factor for infections that emerge later. IgG levels postvaccination do not differ according to age.

Efficacy, effectiveness and immunogenicity of reduced HPV vaccination schedules: A review of available evidence.

Current National Advisory Committee on Immunization (NACI) guidance recommends human papillomavirus (HPV) vaccines be administered as a two or three-dose schedule. Recently, several large clinical trials have reported the clinical benefit of a single HPV vaccine dose. As a result, the World Health Organization released updated guidance on HPV vaccines in 2022, recommending a two-dose schedule for individuals aged 9-20 years, and acknowledging the use of an alternative off-label single dose schedule. The objective of this overview is to provide a detailed account of the available evidence comparing HPV vaccination schedules, which was considered by NACI when updating recommendations on HPV vaccines. To identify relevant evidence, existing systematic reviews were leveraged where possible. Individual studies were critically appraised, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence. Available evidence suggests that a one, two, or three-dose HPV vaccine schedule may provide similar protection from HPV infection. While antibody levels against HPV vaccine types were statistically significantly lower with a single dose schedule compared to two or three doses, titres were sustained for up to 16 years. The clinical significance of lower antibody titres is unknown, as there is no established immunologic correlate of protection. While the available evidence on single-dose HPV vaccination schedules shows a one-dose schedule is highly effective, continued follow-up of single-dose cohorts will be critical to understanding the relative duration of protection for reduced dose schedules and informing future NACI guidance on HPV vaccines.

Humoral immune response and safety of Sars-Cov-2 vaccine in people with multiple sclerosis

BackgroundFor the past three years, the pandemic has had a major effect on global public health, mainly on those with underlying medical conditions, such as people living with Multiple Sclerosis. Vaccination among this group is of great importance, and the long-term impacts of vaccination and its safety on the health of these patients will continue to be revealed. Therefore, risks related to vaccination and immune response need to be assessed. The objective here was to characterize the immune response, short-term safety, and the effects of multiple variables on these factors after COVID-19 vaccination (mainly Sinopharm) among people with Multiple Sclerosis. We assessed the short-term safety and humoral SARS-COV-2 anti-RBD IgG response using a data collection form and Immunoassay, respectively.ResultsNo severe adverse events or MS relapse was observed. Myalgia/body pain (26.7%), low-grade fever (22.2%), and mild headache (15.6%) were the most common adverse events. The use and type of vaccine influenced the frequency of side effects with a p-value < 0.0001. Regarding immune response, patients on rituximab and fingolimod had a lower antibody titer compared to other medications. With a significant difference, hybrid immunity (p-value: 0.047) and type of DMTs (p-value: 0.017) affected the humoral response.ConclusionThere is a low incidence of serious adverse effects, MS worsening or relapse after COVID-19 vaccination, and mainly, side effects are similar to that of the general population. It appears that treatment with various disease-modifying therapies does not induce or worsen the post-vaccination side effects, although some, including Rituximab and fingolimod, may affect the immunity induced after vaccination.