Seronegative Group Research Articles

Are there differences in the clinical and laboratory features of patients with seronegative primary Sjögren's syndrome?

The objective of this study was to demonstrate the commonalities and distinctions between patients with seronegative and seropositive primary Sjögren's syndrome (pSS). The records of 399 patients with pSS seen between January 2010 and June 2023 were retrospectively examined. Patients with negative antiSSA/Ro, antiSSB/La, ANA, and RF antibodies comprised the seronegative group, while patients with at least one positive antibody were included in the seropositive group. The most common clinical features between the groups were arthralgia (81.2%), arthritis (11.5%), hematological involvement (19.8%), and pulmonary involvement (11.8%). In 41 patients (10.3%), no autoantibody positivity was detected. The number of patients with at least one extraarticular involvement was statistically more frequent in the seropositive group (p = 0.011). Dry mouth was found to be more prevalent among seronegative patients (p = 0.003). While hyperimmune gammaglobulinemia exhibited a higher prevalence within the seropositive group (p = 0.004), the occurrence of reduced complement levels was at similar rates in both groups. All deaths were observed exclusively within the seropositive group (17/358, 4.7%). No difference was observed between the two groups concerning mortality (p = 0.237) and malignancies (seropositive group: 9/358, 2.5% vs. seronegative group: 3/41, 7.3%, p = 0.115). There was a statistically significant association between low C4 levels (OR = 2.99 [1.09-8.16], p = 0.045 in model 1, OR = 3.10 [1.14-8.42], p = 0.022 in model 2), and the extraarticular findings. While hematological, renal, pulmonary, and neurological involvements are observed with similar frequency in both seronegative and seropositive pSS patients, the presence of extraarticular manifestations was more common in seropositive patients. Additionally, there was a relationship between extraarticular involvement and low C4 levels.

Cellular and humoral immunity and IgG subclass distribution after omicron XBB.1.5 monovalent vaccination in Japan

BackgroundUp to seven doses of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2) were administered to Japanese healthcare workers, until February 2024. The monovalent Omicron XBB.1.5 vaccine (hereafter called XBB.1.5 vaccine) was used for dose 7. ObjectiveAlthough the XBB.1.5 vaccine has been reported to induce a robust increase in neutralizing antibodies against the currently circulating Omicron variant BA.2.86, little is known about its serological effects in Japan, where the BNT162b2 mRNA vaccine is the most frequently administered in the world. Study designTwenty-five recipients of the XBB.1.5 vaccine, categorized as seronegative (n = 18) or seropositive (n = 7) based on their recent history of COVID-19, were analyzed. Neutralizing antibody titers against Omicron subvariants, receptor binding domain (RBD) IgG levels, IgG subclass distribution, and T-cell responses were assessed. ResultsWe found a significant increase in neutralizing antibody titers against XBB.1.5 and BA.2.86 variants following XBB.1.5 vaccination, particularly in seropositive individuals. No significant change in total RBD IgG levels was observed, indicating efficient induction of antibodies targeting regions outside the RBD by XBB.1.5 vaccination. IgG subclass analysis demonstrated no significant subclass switching after vaccination. T-cell responses against the virus were comparable between seropositive and seronegative groups. ConclusionsThe study suggests that XBB.1.5 vaccination enhances humoral immunity against Omicron variants without significant IgG subclass switching. However, some individuals with low pre-vaccination IgG titers did not exhibit increased antibody levels post-vaccination, raising concerns about potential immune tolerance.

Analysis of clinical features and outcomes in patients with ocular myasthenia gravis according to anti-acetylcholine receptor antibody-seropositivity.

To comparatively analyze the clinical characteristics of patients with ocular myasthenia gravis (OMG) referred to an ophthalmology clinic, according to anti-acetylcholine receptor antibody (AchR Ab)-seropositivity. Retrospective Cohort Study. Medical records of patients with OMG who presented to a tertiary eye care center between 2003 and 2020 were retrospectively reviewed. Demographics, ophthalmologic characteristics, response to medical treatment, presence of autoimmune thyroid disease and thyroid autoantibody were compared between the AchR Ab seropositive and seronegative groups. A total of 130 patients with OMG were identified; among them, 46 patients (35.4%) had autoantibody against acetylcholine receptors. The mean age at symptom onset was 42.4 ± 18.9 years. There were no differences in mean age at symptom onset, gender ratio, and mean follow-up period between patients with seropositive and seronegative OMG. Graves ophthalmopathy was significantly more frequent in seronegative patients (p = 0.04), while thymic disease (p < 0.01) was more frequent in seropositive patients (p < 0.01). Among patients with seropositive OMG, 52.3% showed a good response to medical treatment, while only 31.4% of the seronegative patients were classified as good responders (p = 0.01). Thyroid dysfunction was found in 27.4% patients with OMG and the proportion of thyroid dysfunction was not different according to anti-acetylcholine receptor antibody-seropositivity. Seropositivity to acetylcholine receptor antibody is associated with a better response to medical treatment and lower risk of concomitant autoimmune thyroid disease in patients with OMG.

Autoantibodies in Type 1 Diabetes: prevalence and clinical profiles

Type 1 diabetes mellitus (T1D) is one of the most common chronic diseases in children and is associated with acute and serious chronic complications. T1D is characterized by the destruction of insulin-producing beta cells in the pancreas, with the emergence of circulating autoantibodies (a-Abs) targeting β cell antigens. Identifying autoantibodies can help predict the onset of T1D and associated autoimmune disorders, enhancing patient management strategies.We aimed to determine the prevalence of T1D autoantibodies and their clinical significance in the pediatric and adult populations. A multicenter cross-sectional study was carried out on 276 patient-first with T1D, including 167 pediatric (60.5%) and 109 adult (39.5%) cases, of which 144 were female and 132 were male (sex ratio = 0.91),with an average age of 14.1 ± 8.0 years. The immunological investigation was based on the detection of T1D related a-Abs, including anti-insulin, anti-glutamic acid decarboxylase (GAD65), anti-insulinoma-associated antigen 2 (IA2), and anti-zinc transporter 8 (ZnT8) specificities. The results revealed an overall autoantibody seropositivity rate of 75.36% (n = 208). Among the positive cases, GAD65 antibodies were the most prevalent at 37.31%, followed by anti-insulin and anti-ZnT8 antibodies, each at 36.59%, and anti-IA2 at 28.62%. Additionally, 45,67% of patients had one a-Abs, 28.36% had a two, 21.15% had three, and 4.8% had all four a-Abs.A statistically significant difference was observed between the seropositive and seronegative groups regarding the presence of associated autoimmune diseases (p=0.005). These findings align with the existing literature, highlighting the importance and scientific value of detecting a-Abs in patients with T1D.

Pretransplantation assessment of BK virus seropositivity in kidney donors and recipients

Background: BK virus (BKV) is a member of the polyomavirus family. The determination of anti-BKV immunoglobulin G (IgG) antibody levels in kidney donors and recipients has been reported as a possible predictor of the risk of BK nephropathy. Allograft dysfunction is a significant risk factor. The main objective of this study was to address the high prevalence of renal failure due to BKV nephropathy in kidney transplant recipients. This investigation aims to determine whether donors and recipients of renal transplants had BKV IgG antibodies before transplantation. Methods: Blood samples were collected from 46 kidney transplant recipients and their corresponding 46 donors. An enzyme-linked immunosorbent assay was used to qualitatively analyze human BKV IgG. Results: Ninety-two participants, 46 kidney transplant donors, and 46 kidney transplant recipients, were analyzed. Pretransplantation anti-BKV antibody levels were higher in kidney transplant donors (73%) than in recipients (63%). Donors and recipients included in the study were grouped into seropositive and seronegative recipients, with the highest proportion of seropositive recipient-donor groups (48%) and the lowest percentages in the seronegative donor and seronegative recipient groups. Fifty-one percent of the participants were male and 49% were female. The age distribution of most subjects was &gt;50 years old. Conclusion: BKV can cause kidney transplant rejection. Routine screening of transplant recipients and donors for BKV IgG seropositivity is recommended before renal transplantation. This can improve transplant outcomes and prevent rejection.

Autoantibodies and damage in patients with idiopathic inflammatory myopathies: A longitudinal multicenter study from the MYONET international network

ObjectiveTo study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). MethodsData from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. ResultsA total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. ConclusionOur study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.

Post-vaccine immune status surveillance of Covishield vaccine and associated AEFI in previously SARS-Cov-2 infected seropositive and seronegative population in Assam.

COVID-19 an infectious disease caused by the SARS-CoV-2 virus, started in late 2019 and became a pandemic within a short period. To respond to the pandemic vaccines like Covishield, Covaxin, Sputnik V, Covovax, etc., were developed rapidly. However, there were raising concerns about the development of immunity as well as adverse events following vaccination. To compare anti-SARS-CoV-2 IgG antibody titres at different time-points post-vaccination between baseline seropositive and seronegative groups and to assess the adverse events following the 1st dose of Covishield vaccine among adult beneficiaries attending vaccination centre in a tertiary care hospital of Upper Assam. Prospective Cohort study was conducted from July 2021 to June 2022 among adult beneficiaries receiving the Covishield vaccine. The oral questionnaire was used incorporating socio-demographic variables, and clinical profiles including co-morbidities and adverse events following vaccination. Data analysis was done by Microsoft Excel and SPSS. Out of a total of 146 study participants, IgG estimation showed 61% as seropositive and the rest as seronegative. A total of 55.40% had minor adverse events, majority of them were females (53.08%) and 88.80% belonged to 18-59 years compared to 11.11% above 60 years of age. The majority (71.60%) did not have any co-morbidities and the major AEFI was NIL among the study participants. The study group had 61% seropositive previously infected. Covishield vaccination induces an immune response and 90% seroconversion is achieved after 1st dose (booster dose). Antibody titres of the seropositive group by natural infection of SARS-CoV-2 were higher than seronegative cohort seroconverted by vaccination. The AEFI observed were minor and can be commented as safer.

Perceived fatigue and functional status after mild symptomatic and asymptomatic COVID-19

The aim of the present study was to assess functional performance and perceived fatigue post-COVID-19 in asymptomatic or mildly symptomatic patients. A cross-sectional prospective study was conducted of 1448 individuals who were evaluated for perceived fatigue, functional capacity, handgrip strength, physical activity level, pain and dyspnea. IgG anti-SARS-CoV-2 nucleocapsid serology results and self-declared symptoms were used to classify patients into three study groups: SARS-CoV-2 seronegative, asymptomatic SARS-CoV-2 seropositive and mild infection SARS-CoV-2 seropositive. Participants with a history of moderate or severe COVID-19 were excluded from the analysis. Chi-square test and Kruskal Wallis were used to test for associations between variables. Poisson regression with robust variance was performed for perceived fatigue outcome. Statistical significance was defined as p < 0.05. Measurements for physical performance, body pain or dyspnea between the three study groups were similar. However, a significant difference was observed in reported fatigue between the study groups. Poisson crude and adjusted models confirmed an association between SARS-CoV-2 exposure and presence of perceived fatigue among the asymptomatic and symptomatic mild COVID-19 groups (PR = 1.33 [95%CI:1.09,1.61], P = 0.004 and PR = 1.26 [95%CI:1.03,1.53], P = 0.026), respectively. Upon review, although seropositive SARS-CoV-2 individuals presented a higher prevalence of perceived fatigue, their physical performance was equal to that of the seronegative group.

Serum IgG Immunoglobulin Levels are Associated with Reduced PCR Detection of Mycoplasma bovis in Naturally Infected American Bison (Bison bison).

Mycoplasma bovis (M. bovis) is an important pathogen of American bison (Bison bison), associated with high morbidity and mortality epizootics of respiratory and reproductive disease. Despite the significant negative impact on bison health, little is known about the kinetics of disease and the host immune response to infection. To address these questions, a cohort of bison calves was created and serially sampled 5 times, once every 2-3 mo, over a 12-mo period. At each sampling period nasal swab samples were collected and tested by PCR for the presence of M. bovis. Serum samples were also collected and assessed for M. bovis-specific antibodies using both a commercial and an in-house ELISA. Overall, 19/41 bison (46.3%) had positive PCR tests, and 31/41 (75.6%) were seropositive. Over the course of the study, the frequency of PCR-positive nasal swabs and the ELISA scores decreased, although serum samples remained positive for at least 6 mo following the final positive PCR test. Bison were grouped according to results from the in-house ELISA into high-responder (n=7), low-responder (n=5), and seronegative (n=7) groups. M. bovis-specific IgG antibody levels were significantly elevated in the high-responder group compared to the low-responder and seronegative groups. The differences were statistically significant for 3/5 sampling periods. A trend toward increased IgG2 levels was observed in the high-responder group. High total IgG responses correlated with a decline in positive PCR tests from nasal swabs. These data provide evidence that a strong humoral response is beneficial and is probably involved in the clearance of M. bovis from bison.

Evaluation of serial QuantiFERON-TB Gold in tube test results and tuberculosis infection status in patients with psoriasis receiving anti-IL-17 treatment (secukinumab and ixekizumab): Real-world data from a tuberculosis-endemic country.

In comparison with TNF-α inhibitors, anti-IL-17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation. In this study, we aimed to evaluate the TB infection status and serial QuantiFERON-TB-Gold in tube test (QFT) results of psoriasis patients using IL-17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real-world setting from a tuberculosis-endemic country. Patients who used an anti-IL-17 agent for at least 3 months in our follow-up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records. A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti-IL-17 agent was 14,147 patient-months, 9743 patient-months for SEC and 4404 patient-months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti-IL-17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow-up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected. In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti-IL-17 treatment duration.

Correlation between Melatonin and Colostral Regulatory T Cells in Giardia lamblia Infection.

Giardiasis is a parasitic disease caused by Giardia lamblia (G. lamblia) that affects people worldwide. Still, few studies report on the immunoregulatory effects of the biomolecules of colostrum during interactions with G. lamblia. This study aimed to assess the concentrations of melatonin and cortisol hormones, the percentage of Treg cells, and the levels of cytokines IL-10 and TGF-β in colostrum from mothers who tested positive for the parasite. This cross-sectional study analyzed colostrum samples from 25 puerperal. The samples were tested using an ELISA to determine if they were seropositive for G. lamblia and the type of antibody present (IgM and IgG). Based on the results, the samples were divided into three groups: a control group (N = 10) with no reaction to either IgM or IgG, a group seropositive for IgG (IgG+/IgM-; N = 8), and a group seropositive for IgM (IgM+/IgG-; N = 7). The concentrations of melatonin and cortisol were measured using the ELISA method. Additionally, cytokines IL-10 and TGF-β and immunophenotyping were analyzed using flow cytometry. In the group that tested positive for IgM anti-G. lamblia, the concentration of melatonin was lower. However, in the colostrum from mothers who tested positive for IgG anti-G. lamblia, the level of this hormone had increased. The cortisol levels were similar between the groups, regardless of seropositivity. There was a higher percentage of Treg cells in the colostrum from mothers who tested positive for IgM anti-G. lamblia. TGF-β levels also increased in the colostrum of mothers who tested positive for IgM anti-G. lamblia. In the seronegative group for G. lamblia, there was a positive correlation between melatonin concentration and the percentage of Treg cells. These data suggest that the increase in regulatory cells and cytokines and the reduction in melatonin in colostrum from mothers with recent giardia infection may contribute to the evolution and manifestation of the disease.

#1474 COVID-19-infection in kidney transplant recipients during the omicron surge, a sigh of relief

Abstract Background and Aims The COVID-19 pandemic had a profound impact on global health, particularly affecting high-risk individuals such as solid organ transplant recipients (SOTRs). SOTRs have an elevated risk of severe COVID-19 disease and increased mortality. Kidney transplant recipients (KTRs) vaccinated with mRNA-based vaccines exhibit a lower response rate and shorter half-time of the serologic conversion. However, the percentage of serologic response improves with increasing number of vaccine doses. Studies also indicate that KTRs with prior COVID-19 infection demonstrate a more robust immune response post-immunization compared to COVID-19 naïve patients. Factors such as age, immunosuppressive regimen, eGFR, time since transplantation also impact vaccination response. This study aims to investigate COVID-19 infection outcome and vaccination response among KTRs during the Omicron surge. Method This study is a retrospective single-center cohort study at the Department of Nephrology and Transplantation at Skåne University Hospital in Malmö, Sweden. KTRs infected with COVID-19 during the Omicron surge were included (January 2022 until August 2023). Results 97 KTRs diagnosed with COVID-19 were included of whom 91 were vaccinated. In average, three doses of COVID-19-vaccine had been given to the patients. 67 KTRs showed seroconversion, 28 remained seronegative and the status of the remaining 2 KTRs was unknown. There was a significant association between lack of antibody production and mycophenolic acid (MPA) treatment (P = 0.019, Chi2 test), however the significance was not retained in a multivariate logistic regression analysis. Among the seroconverted (n = 67), 61 experienced mild infection, 5 moderate infection and 1 severe infection, according to the WHO clinical progression scale. In the seronegative group (n = 28), 25 had mild infection while the remaining three had moderate infection. The median time for viral clearance was examined in 79 KTRs and was 23 days (IQR 18-31). Immunosuppression was adjusted in 34% (n = 33) of cases. 2.1% (n = 2) of KTRs experienced graft rejection post infection. Conclusion While most patients experienced a mild infection, unlike during the first surges of the pandemic, the observed subsequent graft rejections emphasize the complexity of COVID-19´s potentially immunologic triggering effect and risk of graft loss in KTRs. The correlation between MPA treatment and a lower degree of serologic conversion after vaccination underscores the need for personalized immunologic follow up and treatment regimen in KTRs.

Clinical Phenotypes, Serological Biomarkers, and Synovial Features Defining Seropositive and Seronegative Rheumatoid Arthritis: A Literature Review.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder which can lead to long-term joint damage and significantly reduced quality of life if not promptly diagnosed and adequately treated. Despite significant advances in treatment, about 40% of patients with RA do not respond to individual pharmacological agents and up to 20% do not respond to any of the available medications. To address this large unmet clinical need, several recent studies have focussed on an in-depth histological and molecular characterisation of the synovial tissue to drive the application of precision medicine to RA. Currently, RA patients are clinically divided into "seropositive" or "seronegative" RA, depending on the presence of routinely checked antibodies. Recent work has suggested that over the last two decades, long-term outcomes have improved significantly in seropositive RA but not in seronegative RA. Here, we present up-to-date differences in epidemiology, clinical features, and serological biomarkers in seronegative versus seropositive RA and discuss how histological and molecular synovial signatures, revealed by recent large synovial biopsy-based clinical trials, may be exploited to refine the classification of RA patients, especially in the seronegative group.

Ultrasonographic Evaluation of the Ankle Joint in Relation to Rheumatoid Factor Status and Disease Activity in Patients with Rheumatoid Arthritis

Abstract Background: Rheumatoid arthritis (RA) is a form of inflammatory disease whose clinical pattern is largely dependent on the presence of both anti-citrullinated protein antibodies and rheumatoid factor (RF). Although this is still debatable, seronegative RA seems to be a somewhat less serious condition. The present study aimed to evaluate ankle joint ultrasound in relation to RF status and disease activity in RA patients. Methods: A cross-sectional study involving RA patients from a single center was conducted. Laboratory test evaluations and clinical activity assessments were carried out. The ankle joint was examined using musculoskeletal ultrasound (US). Results: The study included 100 patients with established RA in total. Eighty-two patients tested positive for RF with a mean age of 42.3, whereas only 18 tested negative with a mean age of 39.6. Patients who tested positive for RF had a longer duration of illness (9.39 ± 5.39 vs. 4.56 ± 3.24). There were no differences in clinical activity scores between the seropositive and seronegative groups. The pathological US findings of any ankle joint showed no differences between the seropositive and seronegative groups. Patients with US findings of tibialis posterior tenosynovitis in the left ankle and synovitis and erosion in the right ankle, particularly in the tibiotalar and talonavicular joints, had significantly high Disease Activity Score 28-Erythrocyte sedimentation rate-scores. The increased disease activity was accompanied by significant erosions on both ankles. Conclusion: In terms of disease activity, there is no clinically significant difference between seropositive and seronegative RA patients. Sonographic ankle joint abnormalities do not appear to be associated with the patients’ RF status. High RA disease activity, on the other hand, is associated with synovitis and erosions, particularly in the talonavicular and tibiotalar joints, as well as tibialis posterior tenosynovitis.

The impact of Toxocara-seropositivity on attention and motor skills in children with attention-deficit hyperactivity disorder

BackgroundThe study aims to compare neurological soft signs and executive functions between Toxocara-seropositive and seronegative groups in children with attention-deficit/hyperactivity disorder. MethodsThe study included 60 boys with ADHD, aged 7–12. After blood samples were taken, the Stroop Color Word Test and Judgment of Line Orientation test (JLOT) were implemented to measure executive functions. Neurological soft signs were evaluated with Physical and Neurological Examination for Subtle Signs (PANESS). ResultsSerological tests were positive for Toxocara antibodies in 20 cases. There was no significant difference between Toxocara seropositive and seronegative regarding age, socioeconomic status, developmental stages, and ADHD severity. However, Toxocara-seropositive children had higher Stroop time and Stroop interference scores and lower JLOT scores than Toxocara-seronegative children. Furthermore, Toxocara-seropositive children exhibited more neurological soft signs, such as gait and station abnormalities, dysrhythmia, and a longer total time in timed movements compared to Toxocara-seronegative children. ConclusionOur study indicates a link between Toxocara-seropositivity and impaired neurological soft signs and executive functions in ADHD. Further research is needed to understand ADHD mechanisms, develop practical treatments considering immunological factors, and thoroughly evaluate how Toxocara seropositivity affects executive functions and motor skills in children with ADHD.

LEVEL OF ALBUMIN IN MALARIA AND HIV CO INFECTED PREGNANT WOMEN, ATTENDING THE ANTENATAL CLINIC OF NNAMDI AZIKIWE UNIVERSITY TEACHING HOSPITAL, NNEWI, SOUTH EASTERN NIGERIA

The purpose of the study was to measure the amount of albumin in pregnant HIV-positive malaria-infected women. Participants in the study were 18 to 40 (36.98 + 5.49) years old, HIV stage 1 and 2 seropositive pregnant women. 80 HIV-positive pregnant women with 40 co-infected with malaria and 80 HIV-negative pregnant women with 40 coinfected with malaria comprised the participant groups. Blood samples were obtained from the subjects for malaria parasite identification using the thick and thin film methods, and HIV status determination using the immunochromatographic approach. The bromocresol green albumin binding method was used to measure the amount of albumin, and the resultant solution was measured spectrophotometrically at 628 nm. In all cases, there was a statistically significant difference in albumin levels between the HIV seronegative group with and without malaria infection (p&lt;0.05) and HIV seropositive group with malaria infection. The mean albumin level of HIV-positive pregnant women who have malaria infection was statistically higher than that of HIV-positive pregnant women who do not have malaria but statistically lower than those of HIV-negative pregnant women with and without malaria infection. The study suggests that pregnant HIV-positive women do not experience a decrease in albumin levels because of malaria infection.

The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies

BackgroundCertain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case.MethodsTo elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed.ResultsGFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80.ConclusionThe 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.

Perinatal dengue and Zika virus cross-sectional seroprevalence and maternal-fetal outcomes among El Salvadoran women presenting for labor-and-delivery.

Despite maternal flavivirus infections' linkage to severe maternal and fetal outcomes, surveillance during pregnancy remains limited globally. Further complicating maternal screening for these potentially teratogenic pathogens is the overwhelming subclinical nature of acute infection. This study aimed to understand perinatal and neonatal risk for poor health outcomes associated with flaviviral infection during pregnancy in El Salvador. Banked serologic samples and clinical results obtained from women presenting for labor and delivery at a national referent hospital in western El Salvador March to September 2022 were used for this study. 198 samples were screened for dengue and Zika virus IgM, and statistical analyses analyzed demographic and clinical outcome associations with IgM positivity. This serosurvey revealed a high rate of maternal flavivirus infection-24.2% of women presenting for labor and delivery were dengue or Zika virus IgM positive, suggesting potential infection within pregnancy. Specifically, 20.2% were Zika virus IgM positive, 1.5% were dengue virus IgM positive, and 2.5% were both dengue and Zika virus IgM positive. Women whose home had received mosquito abatement assistance within the last year by the ministry of health were 70% less likely to test IgM positive (aOR = 0.30, 95%CI: 0.10, 0.83). Further, statistical geospatial clustering revealed transmission foci in six primary municipalities. Pregnancy complications and poor birth outcomes were noted among the dengue and/or Zika virus maternal infection group, although these outcomes were not statistically different than the seronegative group. None of the resulting neonates born during this study were diagnosed with congenital Zika syndrome. The high rate of Zika virus detected among pregnant women and the lack of Zika-specific neonatal outcomes monitoring during a non-outbreak year highlights the need for continued surveillance in Central America and among immigrant mothers presenting for childbirth from these countries. As changing climatic conditions continue to expand the range of the disease vector, asymptomatic screening programs could be vital to early identification of outbreaks and clinical management of cases.

Susceptibility, Immunity, and Persistent Infection Drive Endemic Cycles of Coxiellosis on Dairy Farms.

Coxiella (C.) burnetii, a zoonotic bacterium, is prevalent in dairy farms. Some cows develop a persistent infection and shed C. burnetii into milk and occasionally by amniotic fluid at calving. Serological diagnosis of Q fever in humans is performed by phase (Ph)-specific antibody tests; PhII antibodies usually indicate an acute infection, while the development of a chronic infection is characterised by elevated PhI antibody titres. Phase-specific tests have now been established for diagnosis of coxiellosis in cattle. Additionally, an interferon-γ (IFN-γ) recall assay has been implemented to assess cellular immunity to C. burnetii in cattle. Milk samples from all lactating cows (n = 2718) of 49 Bavarian dairy farms were collected through a convenience sample and analysed for phase-specific antibodies. Antibody profiles were evaluated by age. Based on the seropositivity of first-lactation cows, three distinct herd profiles were observed: an 'acute' state of herd infection was characterised by a PhI-/PhII+ pattern. The detection of PhI antibodies (PhI+/PhII+) characterised the 'chronic' state, and seronegative results defined the 'silent' state of herd infection. If antibodies had not been detected in multiparous cows, the herd was considered as probably free of coxiellosis. The analysed cattle herds were noted to have an 'acute' (n = 12, 24.5%), 'chronic' (n = 18, 36.8%), or 'silent' state of herd infection (n = 16, 32.6%). Only three farms (6.1%) were classified as 'free' of C. burnetii. The detection of these herd states over a time period of 4 years in one farm indicated that the described states occur in a cyclical manner. Frequently, a wave-like profile was seen, i.e., a circumscribed seronegative age group was flanked by seropositive age groups. In seronegative animals, IFN-γ reactivity was demonstrated. Seroconversion after vaccination was observed by day 7 post-vaccination in chronically infected herds, whereas in the case of silent infection, it started by day 14. These data indicated a pre-existing immunity in seronegative animals in chronically infected herds. Additionally, IFN-γ reactivity was detected in seronegative calves (>3 months) and heifers from chronically infected farms compared to a negative farm. An infection prior to 3 months of age resulted in cellular immunity in the absence of detectable antibodies. An infection around calving would explain this. The aforementioned circumscribed seronegative age groups are, therefore, explained by an infection early in life during active shedding at calving. Based on these results, an endemic cycle of coxiellosis is proposed: Susceptible young heifers get infected by persistently infected cows. Subsequently, shedding of C. burnetii at calving results in infection and then in cellular immunity in offspring. When these calves enter the cow herd two years later, a maximum of herd immunity is achieved, shedding ceases, and new susceptible animals are raised. In an acutely infected dairy farm, the PhI+/PhII+ serological pattern prevailed in second-lactation cows. In this study, stored sera collected since birth were analysed retrospectively. From the earliest seroconversion, the peak of seroconversion took about 33 months. These data suggested a slow spread of infection within herds. The classification of dairy cow herds is a promising basis for further analysis of the clinical impact of coxiellosis.

Quantitative brain 18F-FDG PET/CT analysis in seronegative autoimmune encephalitis.

Brain 18F-FDG PET/CT is a useful diagnostic in evaluating patients with suspected autoimmune encephalitis (AE). Specific patterns of brain dysmetabolism have been reported in anti-NMDAR and anti-LGI1 AE, and the degree of dysmetabolism may correlate with clinical functional status.18FDG-PET/CT abnormalities have not yet been described in seronegative AE. We conducted a cross-sectional analysis of brain18FDG-PET/CT data in people with seronegative AE treated at the Johns Hopkins Hospital. Utilizing NeuroQ™ software, the Z-scores of 47 brain regions were calculated relative to healthy controls, then visually and statistically compared for probable and possible AE per clinical consensus diagnostic criteria to previous data from anti-NMDAR and anti-LGI1 cohorts. Eight probable seronegative AE and nine possible seronegative AE were identified. The group only differed in frequency of abnormal brain MRI, which was seen in all of the probable seronegative AE patients. Both seronegative groups had similar overall patterns of brain dysmetabolism. A common pattern of frontal lobe hypometabolism and medial temporal lobe hypermetabolism was observed in patients with probable and possible seronegative AE, as well as anti-NMDAR and anti-LGI1 AE as part of their respective characteristic patterns of dysmetabolism. Four patients had multiple brain18FDG-PET/CT scans, with changes in number and severity of abnormal brain regions mirroring clinical status. A18FDG-PET/CT pattern of frontal lobe hypometabolism and medial temporal lobe hypermetabolism could represent a common potential biomarker of AE, which along with additional clinical data may facilitate earlier diagnosis and treatment.