Seropositive Group Research Articles

Oral Microbial Signature of Rheumatoid Arthritis in Female Patients.

This study aimed to identify the oral microbial signature of Kazakh female rheumatoid arthritis (RA) patients. A total of 75 female patients who met the American College of Rheumatology 2010 classification criteria for RA and 114 healthy volunteers were included in the study. Amplicons of the 16S rRNA gene were sequenced to analyze the microbial composition. We identified significant differences in bacterial diversity and abundance between the RA and control groups, as measured by Shannon (p value = 0.0205) and Simpson (p value = 0.00152) indices. The oral samples from RA patients had higher bacterial diversity than those from non-RA volunteers. The RA samples had a higher relative abundance of Prevotellaceae and Leptotrichiaceae, but a lower content of butyrate and propionate-producing bacteria compared to the control group. The samples from patients in remission had a higher abundance of Treponema sp. and Absconditabacteriales (SR1), whereas those with low disease activity had higher levels of Porphyromonas and those with high RA activity had higher levels of Staphylococcus. A positive correlation was found between the taxa Prevotella_9 and serum levels of antibodies to cyclic citrullinated peptide (ACPA) and rheumatoid factor (RF). The predicted functional pattern of the ACPA+/RF- and ACPA+/RF+ seropositive groups was characterized by increased ascorbate metabolism, degradation of glycosaminoglycans, and reduced biodegradation of xenobiotics. These findings suggest that the functional pattern of the microflora should be considered when selecting a therapeutic strategy for RA in order to provide a personalized approach.

Epstein–Barr virus and cytomegalovirus coinfection in Egyptian COVID-19 patients

BackgroundReactivation of herpesviruses such as Epstein–Barr virus (EBV) and cytomegalovirus (CMV) in COVID-19 patients reported in many studies in different countries during the pandemic. We aimed to measure prevalence of this coinfection in Egyptian COVID-19 patients with elevated liver enzymes and its relation to the severity and the outcome of COVID-19 infection in those patients.MethodsA cross-sectional study was carried out on 110 COVID-19 patients with elevated liver enzymes regardless the severity of COVID-19 disease. All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest). Epstein–Barr virus (EBV) and Human cytomegalovirus (HCMV) were determined by VCA IgM and CMV IgM respectively by enzyme-linked immunosorbent assay (ELISA).ResultsOf the included 110 patients with COVID-19 illness, 5 (4.5%) were Epstein–Barr virus seropositive and 5 (4.5%) were human cytomegalovirus seropositive. Regarding the symptoms, the incidence of fever in the EBV and CMV seropositive group was apparently higher than that in the EBV and CMV seronegative group. In lab tests, the platelets and albumin of EBV and CMV seropositive group decreased more significantly than EBV and HCMV seronegative group, and serum ferritin, D-dimer, and C-reactive protein show higher values in seropositive group than in seronegative group but not statistically significant. Seropositive group had received higher doses of steroids than seronegative group. The median of hospital stay in seropositive group was (15 days) nearly double that of seronegative group with statistically significant difference between both groups.ConclusionCoinfection of EBV and CMV in COVID-19 Egyptian has no effect on the disease severity or the clinical outcome of the disease. But those patients had higher hospital stay duration.

Overlapping and Distinguishing Features Among MS, NMOSD, MOGAD and Other Atypical Demyelinating Syndromes of the Central Nervous System (P11-3.016)

<h3>Objective:</h3> To describe and identify the clinical-demographic, imaging and serological overlapping and distinguishing features among MS, NMOSD, MOGAD, and atypical demyelinating syndromes (ADS) in an attempt to define whether ADS-suggestive diagnostic indicator(s) emerge. <h3>Background:</h3> The era of the enlarging spectrum of MS, NMOSD, MOGAD, and a subgroup of patients with ADS overlapping features has resulted in diagnostic and therapeutic challenges. Since there is a significant diagnostic gap in some patients due to these overlapping features, further research is warranted to describe better diagnostic markers. <h3>Design/Methods:</h3> A total of 204 MS patients fulfilling the McDonald 2017 criteria, 36 AQP4-IgG+ NMOSD patients, 21 double-seronegative NMOSD patients fulfilling the 2015 diagnostic criteria for NMOSD, 15 MOG-IgG+ patients, and 80 ADS patients not fulfilling any of the aforementioned diagnostic criteria were included. Clinical, serological, and neuroimaging findings of the patients were retrospectively evaluated. <h3>Results:</h3> Positive oligoclonal bands (OCBs) in the CSF were found to be significantly higher in the MS and ADS groups than in both seropositive and seronegative NMOSD groups (all p&lt;0.001). The MS group had the highest average number of periventricular (PV) lesions(≥3 lesions) compared with the AQP4+NMOSD and MOGAD groups(no lesions, P&lt;0.001) and the ADS and seronegative NMOSD groups(1–2 lesions, P&lt;0.001). Temporal PV lesions and ovoid PV lesions were significantly higher in MS patients than in ADS patients(both p&lt;0.001). Juxtacortical/cortical (JC/C) lesions were significantly higher in the MS group than in the ADS group(p&lt;0.001). <h3>Conclusions:</h3> Differential features of overlapping demyelinating disorders revealed imaging features such as the presence of temporal PV, ovoid PV, and JC/C lesions, which are highly suggestive of MS, whereas the absence of these imaging features, absence of all diagnostic criteria as well as negative antibody serology but positive OCBs are more common in ADS. Further research and molecular diagnostic markers are required to elaborate on these results and fill this diagnostic gap. <b>Disclosure:</b> Bade Gulec has nothing to disclose. Samet Cam has nothing to disclose. Dr. Bilge has nothing to disclose. Melih Tutuncu has nothing to disclose. Sabahattin Saip, 6729 has nothing to disclose. Ugur Uygunoglu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Turkey . The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Idec/Gen Pharma of Turkey. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen - TR. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abdi Ibrahim Ilac - TR. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen - TR. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono . The institution of Dr. Siva has received research support from Turkish MS Society. The institution of Dr. Siva has received research support from The Scientific and Technological Research Council Of Turkey - Health Sciences Research Grants.

The role of regulatory micro-RNAs in inflammatory processes and production of tumor necrosis factor-alpha in patients with rheumatoid arthritis

Background. Micro-RNAs are fundamental agents of post-transcriptional control of gene expression. In recent years many works have appeared on the possible role of micro-RNAs in rheumatoid arthritis (RA). Studies of the role of micro-RNA and the relationship with the synthesis of tumor necrosis factor-α (TNF-α) are very promising for understanding the pathogenesis and treatment of RA and other autoimmune diseases. The purpose of the research was to study the role of regulatory micro-RNAs in inflammatory processes and the possible connection with the production of TNF-α in patients with RA. Materials and methods. 29 patients with active RA and 20 healthy individuals (control) were examined. All subjects were examined for 16 micro-RNAs. The choice of micro-RNA was based on previous studies and theoretical conclusions (according to the miRWalk database). Rheumatoid factor, the level of antibodies to cyclic peptides containing citrulline, C-reactive protein (СRP), levels of TNF-α (serum, spontaneous, and stimulated) were determined in the blood of patients. Results. Statistical analysis demonstrated significant overexpression of miR-221, miR-203, miR-146b, miR-132, miR-21 and miR-17-3p and inhibition of miR-223 synthesis in RA patients. The activation of TNF-α synthesis at rest and the increased production of TNF-α by mononuclear cells after stimulation in RA were shown. Differences in the levels of relative expression of some micro-RNAs between seropositive and seronegative groups of RA patients were found, but only hyperexpression of miR-155 was highly reliable. For the first time, a possible relationship between TNF-α production and miR-29 and miR-155 micro-RNAs, as well as a correlation between miR-16, miR-99b and miR-203 and CRP levels, was revealed. Conclusions. The obtained data on the profile of micro-RNAs in RA makes it possible to distinguish the most “interesting” micro-RNAs for further study of pathogenesis, their role in inflammation, to study the choice of TNF-α inhibitors, and predicting the effectiveness of that treatment.

Impact of COVID-19 during pregnancy on placental pathology, maternal and neonatal outcome - A cross-sectional study on anemic term pregnant women from a tertiary care hospital in southern India.

SARS-CoV-2 infection during pregnancy may cause adverse maternal, neonatal and placental outcomes. While tissue hypoxia is often reported in COVID-19 patients, pregnant women with anemia are suspected to be more prone to placental hypoxia-related injuries. This hospital-based cross-sectional study was conducted between August-November 2021, during COVID-19 second wave in India. Term pregnant women (N=212) admitted to hospital for delivery were enrolled consecutively. Since hospital admission mandated negative RT-PCR test for SARS-CoV-2 virus, none had active infection. Data on socio-demography, COVID-19 history, maternal, obstetric, and neonatal outcomes were recorded. Pre-delivery maternal and post-delivery cord blood samples were tested for hematological parameters and SARS-CoV-2 IgG. Placentae were studied for histology. Of 212 women, 122 (58%) were seropositive for SARS-CoV-2 IgG, but none reported COVID-19 history; 134 (63.2%) were anemic. In seropositive women, hemoglobin (p=0.04), total WBC (p=0.009), lymphocytes (p=0.005) and neutrophils (p=0.02) were significantly higher, while ferritin was high, but not significant and neutrophils to lymphocytes (p=0.12) and platelets to lymphocytes ratios (p=0.03) were lower. Neonatal outcomes were similar. All RBC parameters and serum ferritin were significantly lower in anemic mothers but not in cord blood, except RDW that was significantly higher in both, maternal (p=0.007) and cord (p=0.008) blood from seropositive anemic group compared to other groups. Placental histology showed significant increase in villous hypervascularity (p=0.000), dilated villous capillaries (p=0.000), and syncytiotrophoblasts (p=0.02) in seropositive group, typically suggesting placental hypoxia. Maternal anemia was not associated with any histological parameters. Univariate and multivariate logistic regression analyses of placental histopathological adverse outcomes showed strong association with SARS-CoV-2 seropositivity but not with maternal anemia. When adjusted for several covariates, including anemia, SARS-CoV-2 seropositivity emerged as independent risk factor for severe chorangiosis (AOR 8.74, 95% CI 3.51-21.76, p<0.000), dilated blood vessels (AOR 12.74, 95% CI 5.46-29.75, p<0.000), syncytiotrophoblasts (AOR 2.86, 95% CI 1.36-5.99, p=0.005) and villus agglutination (AOR 9.27, 95% CI 3.68-23.32, p<0.000). Asymptomatic COVID-19 during pregnancy seemed to be associated with various abnormal placental histopathologic changes related to placental hypoxia independent of maternal anemia status. Our data supports an independent role of SARS-CoV-2 in causing placental hypoxia in pregnant women.

Assessment of Prognostic Factors and Validity of Scoring Models in Childhood Autoimmune Encephalitis.

The aim of this study is to evaluate the prognostic factors in a single-center pediatric cohort with autoimmune encephalitis. The study group consisted of 23 pediatric autoimmune encephalitis patients (seropositive autoimmune encephalitis: 15, seronegative autoimmune encephalitis: 8). Five group prognostic parameters were evaluated: clinical manifestations, elect roenc ephal ograp hy features, magnetic resonance imaging characteristics, biomarkers, and treatment modalities. Three scoring models were applied: the Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy for predicting autoimmune-related epilepsy in the whole cohort and the anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score for overall outcome in patients with anti-N-methyl-d-aspartate receptor encephalitis. The initial clinical spectrum of the disease was similar in the seronegative and seropositive groups. Almost half of the patients (48%) recovered without any complications with first-line immunotherapy. The patients with movement disorders in the acute phase of the disease needed more likely second-line immunotherapy (P = .039). The presence of status epilepticus at admission was significantly associated with adverse outcomes and the development of autoimmune-related epilepsy (P = .019). Autoimmune-related epilepsy was defined in an equal proportion of patients (91.5%) with 2 immune epilepsy scores (Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy). The N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score and the modified Rankin score assessed for the first-year prognosis were strongly correlated among the patients with anti-N-methyl-d-aspartate receptor encephalitis (P = .03, Spearmen's rho = 0.751). The presence of status epilepticus was the most important prognostic factor in the patients with the adverse outcome. The studied scoring models (Anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status, Antibody Prevalence in Epilepsy, and Response to Immunotherapy in Epilepsy) have also been proven to be applicable to the pediatric age group for predicting overall outcome and autoimmune-related epilepsy.

SG-APSIC1049: Immunogenicity of Gam-COVID-Vac and Sinopharm BBIBP-CorV vaccines in seropositive and seronegative adults

Objectives: Data comparing the immunogenicity of Sputnik-V and Sinopharm vaccines in seropositive and seronegative groups are lacking. We compared the immunogenicity of Sputnik-V (Gam-COVID-Vac) and Sinopharm (BBIBP-CorV) vaccines in seronegative and seropositive groups. Methods: In total, 60 adults participated the study. The immune response after vaccination was assessed using enzyme immunoassay. IgG levels were measured in all participants at 3 time points: before vaccination, 42 days after the first vaccine dose, and 6 months after the first vaccine dose. The results of the SARS-CoV-2 antibody test were quantified according to the WHO First International Standard and expressed in international units (BAU per mL). Results: The study participants were divided into 2 groups: 30 people (50%) were vaccinated with Sputnik-V (Gam-COVID-Vac) and 30 people (50%) were vaccinated with Sinopharm (BBIBP-CorV). The groups had no difference in sex composition. The highest antibody levels were observed 42 days after vaccination in both the seronegative group (P = .006) and the seropositive group (P &lt; .001). At 6 months after vaccination, the IgG value declined much farther among the seronegative group (P = .003) compared to those who had recovered from COVID-19 before vaccination. However, the “hybrid immunity” generated by the Sputnik-V vaccine had greater strength and duration (P &lt; .001). Conclusions: This study showed that IgG levels in vaccinated individuals who previously recovered from SARS-CoV-2 infection (“hybrid immunity”) were higher than in SARS-CoV-2–naïve individuals. In a comparative part of the study, the Sputnik-V vaccine had greater strength and duration of immune response across the 6-month observation period (P &lt; .001).

Assessment of intelligence quotient in patients with neuromyelitis optica spectrum disease and multiple sclerosis.

Cognitive impairment is common in people living with neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS). However, there is little published data on intelligence quotient (IQ) in NMOSD patients. Therefore, we performed the present study to compare IQ scores across NMOSD, MS, and control groups. In this cross-sectional study, 49 NMOSD (30 with positive aquaporin4 antibody), 41 MS, and 20 control individuals were recruited. The IQ score for each person was measured using Wechsler Adult Intelligence Scale-Revised (WAIS-R). Participants were reported on eleven scores of subsets, verbal IQ (VIQ), performance IQ (PIQ), and full score IQ (FSIQ). The scores of FSIQ, VIQ, PIQ, vocabulary, similarities, and digit-symbol in NMOSD and MS individuals were lower than the control group. Relative to control, NMOSD patients reported a lower score of information. We found no difference between NMOSD and MS groups, except in vocabulary and similarities. No significant difference between seropositive and seronegative NMOSD groups was observed except for the information and block design. In NMOSD group, a greater EDSS score was associated with decreased scores of FSIQ, VIQ, and PIQ. Being employed and being married were associated with greater scores of VIQ and PIQ, respectively. In both NMOSD and MS groups, advanced education was associated with increased scores of FSIQ and VIQ. Our study showed decreased IQ scores in NMOSD and MS. Further studies are required to examine intellectual quotient in people with NMOSD and MS.

Is there a higher risk of exposure to Coxiella burnetii for pre-clinical veterinary students?

Coxiella burnetii is globally distributed but evidence of zoonotic transmission in the Caribbean region is scarce. The bacterium presence is suspected on the Caribbean island of St. Kitts. The risk of exposure of veterinary students was reported in other regions of the world but is not documented in the Caribbean region. The present study aimed to evaluate the risk of exposure to C. burnetii for pre-clinical veterinary students (mostly coming from the U.S.) attending an island-based veterinary school.A cross-sectional study was conducted to compare incoming and outgoing veterinary students' seroprevalence. Serology was performed using indirect immunofluorescence assay to test Coxiella burnetii Phase I and Phase II immunoglobulins M and G. Background data were gathered using a standardized questionnaire. A parallel study enrolled veterinary school employees in the same university.Of the 98 participants (48 incoming and 50 outgoing students), 41 (41.8%, 95 %CI: 31.9–52.2) were seropositive to C. burnetii. There was no significant difference between the two groups (45.8% for incoming vs. 38.0% for outgoing students) (p = 0.4). No risk factors (demographic, animal handling practices or background) were significantly more reported in the seropositive group. In the employee study, the seroprevalence was high with 8/15 seropositives (53.3%, 95 %CI: 26.6–78.7).Pre-clinical veterinary students do not have a higher risk of exposure to C. burnetii by attending the veterinary school in St. Kitts, but they are highly exposed before arrival on the island (seroprevalence of 45.8%). Most of these participants had experience with animals either through farming or previous veterinary technician employment. This indicates a high exposure in the U.S. young population aiming to become veterinarians. There is an urgent need to increase C. burnetii surveillance in animals and humans to apply relevant prevention and control measures, including recommendations for vaccination of students and professionals at risk.

Typing of HLA-A, -B and DRB1 antigens in clinical practice in patients of the Rostov population for early diagnosis of rheumatoid arthritis

Objective: a retrospective analysis of the results obtained by typing HLA-A, -B antigens and HLA DRB1 allele groups in patients with rheumatoid arthritis (RA) in the Rostov population.Materials and methods: typing of patients with rheumatic inflammatory diseases who were on inpatient treatment in the rheumatology department of the SBI “OKB No. 2” was carried out in the LITT SBI RO "BTS" in 2019-2020. 41 patients (9 men, 32 women, median age — 42 years) were diagnosed with RA. All patients were typed by HLA-DRB1 alleles by real-time polymerase chain reaction with DNA-TECH reagents (Russia). To isolate DNA, a set of Sample-Rapid-Genetics was used by NPO DNA Technology LLC. 39 patients were typed аccording to HLA-A, -B. Typing was carried out by a standard lymphocytotoxic test with DILEN reagents (Czech Republic). Lymphocytes were isolated in a density gradient of “Lympholot”, DILEN company. The control group consisted of healthy residents of the Rostov population (donors of the hematopoietic stem cell registry).Results: a retrospective analysis showed that HLA DRB1*04 occurs in 46.3% of the Rostov population with RA, in 61.1% of the seropositive RA group (control — 20%). There was a decrease in the frequency of HLA DRB1*13 (9.7%) compared to the control (24.4%).Conclusions: the high level of reliability (p&lt;0.001) of the increase in the frequency of HLA DRB1*04 alleles confirms their associative relationship with RA in the Rostov population. A decrease in the frequency of HLA DRB1*13 indicates the protective function of these alleles in RA. Typing results are important for early diagnosis of RA.

Sero-detection of Epstein-Barr virus and Cytomegalovirus Antibodies among patients with Systemic lupus Erythematous in Sudan

Infection by Cytomegalovirus (CMV) and Epstein - Barr virus (EBV) has been implicated in the pathogenesis of Systemic lupus Erythematous (SLE). The current study aimed to determine the frequency of EBV and CMV IgG among Sudanese patients with SLE. A case-control analytical study was conducted on 82 participants in Khartoum State during the period from 2017 to 2018. Serum from patients with SLE (n=62), and controls participants (n=20) were tested for IgG antibodies against EBV and CMV using the Avidity ELISA assay. Pretested questionnaire data were analyzed by SPSS software V.20 (IBM, Chicago,IL). Means and proportions of the demographic were calculated for SLE seropositive groups. Chi-square test and binary logistic regression analysis were used for SLE as a dependent factor while IgG seropositive groups of EBV and CMV as the independent variable and, SLE variables as dependent variables. Odds ratio (OR) with a 95% confidence interval was calculated and statistical significance was defined as a P value below 0.05. Eighty-two females with SLE volunteered to participate in this study, including 62 cases with systemic lupus erythematosus and 20 control participants. Average age means ± SD (34±1.4) for cases and (34±1.6) for controls. Original tribes in Sudan were screened Avidity assay for Western State 37(45.1%), Northern State 29(35.4%), Central State 17(20.7%), and Southern State1 (1.2%) respectively. Seropositivity of IgG by Avidity assay revealed high score for CMV 60 (96.8%) among cases vs 19(95%) among controls, (OR 1.579, CI -95% (0.136-18.4), P &lt;0.05). Seropositivity for both EBV and Co-infection was 58 (98.3%) vs 16 (80.0%) among cases and controls, respectively (OR 3.625, CI -95% (0.227-2.708), P &lt;0.05). Patients with SLE in Sudan have a high rate of infections by EBV and CMV as evidenced by the IgG avidity test indicating association.

Anti-Aspergillus fumigatus IgG in patients with bronchiectasis and its relationship with clinical outcome

Aspergillosis is a mycosis, most commonly affecting the airways. This mycosis can worsen the clinical condition of patients with concurrent lung diseases. We assayed for the presence of serum anti-A. fumigatus IgG in bronchiectasis patients from a tertiary hospital in south Brazil and evaluated the relationship with clinical outcome. Thirty-one patients with bronchiectasis, without cystic fibrosis, were included. Clinical and epidemiological data were collected from all participants. Positive serological tests were detected in 13% (4/31) of the patients. The mortality rate for the year following the assay was, in the seropositive group, 75% (3/4), whereas in the seronegative group, 15% (4/27). An illustrative case is also shown and discussed. Our study highlights the diagnostic challenge and the possible impact of Aspergillus infection on these patients, indicating the necessity of more and larger investigations in the field.

Sars-Cov-2-Specific CD4+ and CD8+ T Cell Responses Can Originate from Cross-Reactive CMV-Specific T Cells

Introduction: SARS-CoV-2-specific CD4+ and CD8+ T cells play an important role in COVID-19 pathogenesis. In addition to de novo SARS-CoV-2-specific T cell responses in infected individuals, SARS-CoV-2-specific T cells have also been identified in samples frozen down before the pandemic. So far, pre-existing SARS-CoV-2 specific T cell responses has mostly been ascribed to cross-reactive T cells that were initially primed by other coronaviruses. The presence of these cross-reactive T cells is not surprising considering these human coronaviruses share a relatively high sequence homology. However, T cells are also able to cross-react towards dissimilar pathogens, called heterologous immunity. Given the high prevalence and magnitudes of pre-pandemic SARS-CoV-2-specific T cells, we hypothesized that pre-pandemic SARS-CoV-2 T cell immunity could be explained by cross-reactive cytomegalovirus (CMV)-specific T cells. Methods & Results: PBMCs from CMV seropositive and seronegative donors that were cryopreserved before the pandemic were incubated with SARS-CoV-2 peptide pools. To detect SARS-CoV-2-specific T cells using flow cytometry, CD4+ T cell responses were identified by upregulation of CD154 and CD137 whereas CD8+ T cell responses were identified by upregulation of CD137 and IFN-γ production. In the CMV seropositive group, clear CD4+ T cell responses against SARS-CoV-2 membrane and CD8+ T cell responses against SARS-CoV-2 spike were detected whilst this was not observed in CMV seronegative donors. To investigate whether these T cells were reactive against both SARS-CoV-2 and CMV, the SARS-CoV-2 reactive T cells were single cell sorted, clonally expanded, and tested in co-culture assays in which stimulator cells expressing the relevant human leukocyte antigen (HLA) alleles were pulsed with overlapping peptide pools, peptide libraries or single peptides. The results demonstrated that the pre-pandemic SARS-CoV-2 membrane-specific CD4+ T cells recognized both SARS-CoV-2 membrane and CMV-pp65 peptide pools in HLA-DRB3*02:02, and specifically recognized AGILRNLVPM peptide of CMV-pp65. The pre-pandemic SARS-CoV-2 spike-specific CD8+ T cells recognized spike peptide FVSNGTHWF (FVS) and, interestingly, dissimilar CMV-pp65 peptide IPSINVHHY (IPS) both presented by HLA-B*35:01. Importantly, these FVS/IPS-cross-reactive T cells displayed a higher avidity for CMV compared to SARS-CoV-2, which illustrates that these cells were originally primed against CMV since repeated antigen exposure results in a selection for high avidity T cell clonotypes. This selection cannot have occurred in response to SARS-CoV-2-specific peptides in SARS-CoV-2-unexposed individuals. PBMCs from pre-pandemic CMV-seropositive donors that express HLA-B*35:01 were screened for the presence of these dual IPS/FVS-specific CD8+ T cells by peptide-HLA tetramer technology. In multiple donors these cross-reactive T cells were detected, and isolation followed by direct T cell receptor (TCR) sequencing of the IPS/FVS-tetramer positive cells showed that these T cells express an amino acid-identical TCR, illustrating that this SARS-CoV-2/CMV cross-reactivity of the IPS/FVS T cells is caused by a public TCR. To investigate the potential of the IPS/FVS-specific T cells to kill virus-infected cells, and thereby reducing spreading of SARS-CoV-2, the T cells were incubated with SARS-CoV-2-infected airway epithelial Calu-3 cells. Intracellular SARS-CoV-2 RNA was reduced at low virus titers in IPS/FVS-specific T cell co-cultures, indicating that the cross-reactive T cells are killing SARS-CoV-2-infected cells and thereby reduce spreading of SARS-CoV-2 during initial infection. Circulating IPS/FVS-specific T cells were not phenotypically activated in two patients with advanced COVID-19, as measured by flow cytometry analysis of CD38 and HLA-DR expression, indicating that cross-reactive T cells may more likely play a role during early stage of infection. Conclusion: CMV-specific T cells cross-react with SARS-CoV-2, despite low sequence homology between the two viruses, and may contribute to the pre-pandemic immunity against SARS-CoV-2. Pre-print link: https://www.biorxiv.org/content/10.1101/2022.07.31.502203v1

In the presence of non-neutralising maternally derived antibodies, intradermal and intramuscular vaccination with a modified live vaccine against porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) induce similar levels of neutralising antibodies or interferon-gamma secreting cells

The purpose of this study was to compare the immune response generated by the intramuscular and the intradermal vaccination route against the porcine reproductive and respiratory syndrome virus (PRRSV). Piglets from a seronegative and a seropositive farm were selected (n = 28 piglets per farm), and each group was divided into two groups and vaccinated after weaning with modified live vaccine Unistrain® PRRS (Laboratorios Hipra Amer, Spain) by the intramuscular (IM) or the intradermic (ID) route. For the following 6 weeks, animals were weekly bled to assess the humoral response by PRRSV-specific antibody ELISA and viral neutralisation test. At 0-, 3-, 4- and 6 weeks post-vaccination, peripheral mononuclear blood cells (PBMC) from eight animals per group were recovered to analyse cellular response by IFN-γ ELISPOT and lymphoproliferation. Serum IL-12 was also quantified by ELISA. Seroconversion was first detected 14 days post-vaccination (dpv) for both IM and ID routes, and peaked at 35 dpv (both IM groups and ID seropositive) or 42 dpv (ID seronegative). At 3 weeks after vaccination, 6/27 (22.22%) animals from negative origin had not seroconverted, and neutralising titres were significantly lower at 35 dpv compared to the seropositive origin (mean log2 titres of 1.36 and 4.25 respectively) Also, it was 10 times more probable for them to have high levels of IL-12 a week after vaccination than for animals of seropositive origin. Cellular immune response analysed by lymphoproliferation and IFN-γ ELISPOT was already present at 21 dpv and until 42 dpv, with no significant differences between groups except for a higher lymphoproliferation at 35 dpv in the IM seropositive group (Kruskal-Wallis, p < 0.05). These results indicate that the intradermal route induces an immune response equivalent to the classical intramuscular route even in presence of non-neutralising maternal immunity, which in this study has proven to facilitate seroconversion after vaccination with an heterologous strain.

Prevalence of Syphilis Infections Among Volunteer Blood Donors in Jinan Blood Center, China: A 15-Year Retrospective Study.

Syphilis infections among volunteer blood donors increased rapidly in recent years. It is important to analyze the demographics of seropositive donor groups and help to recruit donors from low-risk population. The aim of this study was to analyze the syphilis prevalence among volunteer blood donors in Jinan Blood Center and give direction to blood recruitment. A cross-sectional study was conducted among blood donors in Jinan, China. Socio-demographic data and blood donation testing data from January 2007 to December 2021 were extracted from the database of blood management software of Jinan Blood Center for analysis. All blood samples were screened by ELISA, and those anti-TP-positive samples were counted and analyzed by sex, age, educational background, occupation and blood donation times. Logistic regression was used to explore risk factors associated with syphilis infection. Totally 700,757 blood samples were collected in the study during 2007 to 2021, 2290 cases were detected anti-TP positive with a positive rate of 0.33%. Female, 35-44 years old, with a lower education degree, farmers and first-time donors were the high-risk subgroups. Consultation and identification of high-risk population groups should be improved. Measures should be taken to make the donor recruitment more professional and detailed.

Correlation between latent toxoplasmosis and thyroid hormone levels in sera of schizophrenic patients

Latent toxoplasmosis is a prevalent chronic infection caused by a protozoan parasite called Toxoplasma gondii. Recent studies have shown that T. gondii may affect thyroid hormone levels and thus induce behavioral alteration. However, this correlation has been inadequately investigated. Therefore, we aimed to examine the relationship between latent toxoplasmosis and thyroid hormone levels in schizophrenic patients. For this purpose, blood samples and sociodemographic information were collected from 101 schizophrenic patients attending three psychiatric hospitals in Kurdistan region of Iraq. Anti-T. gondii-IgG antibodies and thyroid hormones levels (TSH, T3, T4) were determined in sera of all patients using ELISA technique. Anti-T. gondii-IgG antibodies were detected in sera of 40 (39.6%) out of 101 schizophrenic patients. Logistic regression analysis showed significant association between toxoplasmosis and schizophrenic patients in 50-60 age group (OR=6.177, p=0.05), and un-employed patients (OR=3.562, p=0.05). Data analysis showed non-significant difference in TSH levels between IgG seropositive and IgG seronegative group (p&gt;0.05). On the other hand, T4 levels were significantly higher in the seropositive (10.16 ± 2.61) than seronegative group (7.01 ± 2.01), with highly significant positive correlation between IgG and T4 levels (p= 0.001). Finally, T3 levels were significantly higher in the seropositive (1.91 ± 0.5) than seronegative group (1.12 ± 0.43), with non-significant positive correlation between IgG and T3 levels (p=0.30). Owing to the fact that there was statistically significant increase in thyroid hormone levels in T. gondii seropositive patients, our results suggest that there is a significant association between toxoplasmosis and thyroid hormone levels in schizophrenic patients.

Impact of latent toxoplasmosis on thyroid diseases during gestation

Toxoplasmosis is among the most widely diseases that distributed by the protozoan parasite Toxoplasma gondii. So in the case of pregnancy, latent toxoplasmosis is a risk factor which causes thyroid disease. The aim of the study was to determine the effect of latent toxoplasmosis on thyroid diseases during gestation. 214 blood samples were collected from pregnant women who admitted to different hospitals in Erbil governorate. ELISA technique was used for detecting Toxoplasma IgG antibody, as well as determining serum levels of thyroid hormone levels. Overall, 23.37% of tested samples were Toxoplasma gondii IgG seropositive. Latent toxoplasmosis has a positive correlation with thyroxin (T4) (p=0.026), however, no significant correlation was found with both thyroid stimulating hormone (TSH) and triiodothyronine (T3) (p&gt;0.05). No significant differences were found between Toxoplasma IgG seropositive and seronegative groups as related to trimester, age, city, place, blood group, occupation, food habit, animal contact, disease, and vitamin D level, except the characteristic of abortion, which was significant at a p=0.042. In conclusion, latent toxoplasmosis had significant impact on the occurrence of T4 secretion during gestation. Whereas, TSH and T3 had no significant association with latent toxoplasmosis. Increasing the awareness of toxoplasmosis among pregnant women is required to avoid their deleterious effects, which has a notable impact on lowering the rate of abortion caused by this parasite.

Scenario of viral and protozoa diseases in commercial dairy goats from Zona da Mata of Minas Gerais State, Brazil

Caprine encephalitis-arthritis virus (CAEV), bluetongue virus (BTV), and the parasites Neospora caninum and Toxoplasma gondii can be considered important infectious agents for dairy goats, causing significant losses in production. Bovine herpesvirus 1 (BHV-1) and vesicular stomatitis virus (VSV) can occasionally infect goats. This study assessed the prevalence and determined the risk factors for viral (CAEV, BTV, BHV-1, and VSV) and protozoan (T. gondii and N. caninum) infection; it also verifies the natural disposition of seropositive groups regarding their multivariate similarity in commercial dairy goat farms in the Zona da Mata of Minas Gerais, Brazil. Blood serum samples from 413 dairy goats from nine farms were analyzed using the virus neutralization test, agar gel immunodiffusion, and indirect immunofluorescence methods. The average prevalences found were 65% (269/413) and 47.1% (195/413) for the parasites N. caninum and T. gondii and 35% (145/413) and 24% (99/413) for BTV and CAEV, respectively. All samples were seronegative for BHV-1 and VSV. Significant risk factors were found only in T. gondii and CAEV infection. For toxoplasmosis, contact of the herd with cats (OR = 28.6; [95% CI = 5.81–140.66]) or dogs and cats (OR = 21.12; [95% CI = 6.78–65.82]), the disposal of dead animals in landfill (OR = 0.03; [95% CI = 0.01–0,10), the lack of colostrum treatment (OR = 3.75 [95% CI = 1.53–9.20]), and natural reproduction (OR = 0.28; [95% CI = 0.13–0.62]) were risk factors. For CAEV, the risk factors were contact with dogs (OR = 0.66; [95% CI = 0.49–0.90]), the disposal of dead animals in landfill (OR = 4.12; [95% CI = 1.65–10.28]), and natural suckling (OR = 0.03; [95% CI = 0.004;0.261]). Based on the PCA results, farms with higher rates of positive cases in CAEV, N. caninum, and T. gondii infection bordered the mesoregion, demonstrating the possible special interaction with the seropositivity of dairy goat herds. There is a need to implement measures to control viral and protozoal infections in this important goat milk production region in Brazil.

Association of the serological status of rheumatoid arthritis patients with two circulating protein biomarkers: A useful tool for precision medicine strategies.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and presence of systemic autoantibodies, with a great clinical and molecular heterogeneity. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are routinely used for the diagnosis of RA. However, additional serological markers are needed to improve the clinical management of this disease, allowing for better patient stratification and the desirable application of precision medicine strategies. In the present study, we investigated those systemic molecular changes that are associated with the RF and ACPA status of RA patients. To achieve this objective, we followed a proteomic biomarker pipeline from the discovery phase to validation. First, we performed an iTRAQ-based quantitative proteomic experiment on serum samples from the RA cohort of the Hospital of Santiago de Compostela (CHUS). In this discovery phase, serum samples from the CHUS cohort were pooled according to their RF/ACPA status. Shotgun analysis revealed that, in comparison with the double negative group (RF-/ACPA-), the abundance of 12 proteins was altered in the RF+/ACPA+ pool, 16 in the RF+/ACPA- pool and 10 in the RF-/ACPA+ pool. Vitamin D binding protein and haptoglobin were the unique proteins increased in all the comparisons. For the verification phase, 80 samples from the same cohort were analyzed individually. To this end, we developed a Multiple Reaction Monitoring (MRM) method that was employed in a comprehensive targeted analysis with the aim of verifying the results obtained in the discovery phase. Thirty-one peptides belonging to 12 proteins associated with RF and/or ACPA status were quantified by MRM. In a final validation phase, the serum levels of alpha-1-acid glycoprotein 1 (A1AG1), haptoglobin (HPT) and retinol-binding protein 4 (RET4) were measured by immunoassays in the RA cohort of the Hospital of A Coruña (HUAC). The increase of two of these putative biomarkers in the double seropositive group was validated in 260 patients from this cohort (p = 0.009 A1AG1; p = 0.003 HPT). The increased level of A1AG1 showed association with RF rather than ACPA (p = 0.023), whereas HPT showed association with ACPA rather than RF (p = 0.013). Altogether, this study has allowed a further classification of the RA seropositive patients into two novel clusters: RF+A1AG+ and ACPA+HPT+. The determination of A1AG1 and HPT in serum would provide novel information useful for RA patient stratification, which could facilitate the effective implementation of personalized medicine in routine clinical practice.

Efficacy and safety of the SARS-CoV-2 mRNA vaccine in lung transplant recipients: a possible trigger of rejection.

ObjectiveSolid organ transplant recipients have an increased risk of developing severe coronavirus disease 2019 (COVID-19). Although SARS-CoV-2 mRNA vaccination has been strongly recommended for solid organ transplant recipients, its efficacy and safety have remained unknown.MethodsWe performed an observational prospective cohort study in 18 lung transplant recipients who received two doses of SARS-CoV-2 mRNA vaccine, including BNT162b2 (n = 17) or mRNA-1273 (n = 1), between June and October 2021. The titers of IgG antibodies against the SARS-CoV-2 spike protein (S-IgG) were measured in serum samples collected before the prime dose, three weeks after the prime dose, and four weeks after the booster dose. Reactogenicity and adverse events were evaluated after vaccination.ResultsThere were no recipients with previous SARS-CoV-2 infection prior to vaccination. S-IgG levels were elevated in 2/18 (11.1%) recipients after the prime dose and in 5/18 recipients (27.8%) after the booster dose (31.7 ± 30.6 U/ml). The time from transplantation to vaccination tended to be longer in the seropositive group than the seronegative group [7.5 (3.9–10.2) vs 2.8 (1.9–4.0) years, p = 0.059]. Maintenance dose of mycophenolate mofetil tended to be lower in the seropositive group than in the seronegative group [500 (250–500) vs 1000 (1000–1000) mg/day, p = 0.088]. Regarding the adverse events after vaccination, the development of chronic lung allograft dysfunction (CLAD) or antibody-mediated rejection (AMR) were observed in two seropositive patients.ConclusionsThe antibody response to the SARS-CoV-2 mRNA vaccine was quite poor in lung transplant recipients. We experienced cases that developed clinical CLAD or AMR that was likely related to SARS-CoV-2 vaccination.