Seronegative Controls Research Articles

Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity.

Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.

Symptom Burden and Immune Dynamics 6 to 18 Months Following Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2): A Case-control Study.

BackgroundThe burden and duration of persistent symptoms after non-severe COVID-19 remains uncertain. This study aimed to assess post-infection symptom trajectories in home-isolated COVID-19 cases compared to age- and time-period matched seronegative controls, and investigate immunological correlates of long COVID.MethodsA prospective case-control study conducted between February 28th and April 4th 2020 included home-isolated COVID-19 cases followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched SARS-CoV-2 naive controls. We collected clinical data at baseline, 6, 12 and 18 months post-infection, and blood samples at 2, 4, 6 and 12 months for analysis of SARS-CoV-2 specific humoral and cellular responses.ResultsOverall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared to controls, adult cases had a high risk of fatigue (27% excess risk, gender and comorbidity adjusted odds ratio [aOR] 5.86, 95% confidence interval [CI]3.27-10.5), memory problems (21% excess risk, aOR 7.42, CI 3.51-15.67), concentration problems (20% excess risk, aOR 8.88, CI 3.88-20.35), and dyspnea (10% excess risk, aOR 2.66, CI 1.22-5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%, CI 1.5, 21.5, p = 0.024) and among women (excess risk 18.7%, CI 4.4, 32.9, p = 0.010). Longitudinal spike IgG was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4 + TCRβ depth was significantly associated with both dyspnea and number of symptoms at 12 months.ConclusionsThis study documents a high burden of persisting symptoms after mild COVID-19, and suggest that infection induced SARS-CoV-2 specific immune responses may influence long-term symptoms.

Radiographic aspects in individuals infected by human T-lymphotropic virus type 1 (HTLV-1) with joint pain

BackgroundJoint pain in the absence or with little synovitis is observed in a large percentage of HTLV-1 infected subjects. As the virus infect CD4 + and CD8 + positive, macrophages and B cells an exaggerated production of pro-inflammatory cytokines is detected in these patients. However, the possible association of HTLV-1 infection with autoimmune diseases has not been documented definitively and the clinical characteristics of HTLV-1 associated arthropathy has not been defined. The objective this study is to describe clinic and radiographic features in HTLV-1-infected individuals with complaints of joint pain.MethodsCross-sectional study enrolling HTLV-1-infected individuals with chronic joint pain, aged up to 75 years, both genders and seronegative controls with osteoarthritis. All participants underwent conventional radiography of the hips, knees and ankles.ResultsEighty-one HTLV-1 infected patients and 30 subjects with osteoarthritis participated in the study. Polyarticular and symmetrical arthritis prevailed in the HTLV-1 positive group (54%), while oligoarticular and asymmetrical (44%) were more common in controls (p < 0.05). The frequency of enthesophytes (90%) in HTLV-1-infected patients was greater than in the control group (73%) (p < 0.05). Radiographic features were similar in HTLV-1 carriers and in patients with probable or definite HTLV-1 associated myelopathy. The presence of enthesophytes in the absence of joint space reduction or osteophytes was only observed in HTLV-1-infected individuals (p < 0.001). Magnetic resonance imaging of the ankles of five HTLV-1-infected patients and five controls demonstrated a higher frequency of enthesitis, bursitis and osteitis in the HTLV-1 infected group.ConclusionHTLV-1-associated arthropathy is clinically characterized by symmetrical polyarthralgia and the main radiological finding is the presence of enthesophytes in the absence of osteophytes and joint space narrowing.

Association of Plasma Eicosanoid Levels With Immune, Viral, and Cognitive Outcomes in People With HIV.

Background and ObjectivesTo determine whether plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people with HIV (PWH).MethodsWe measured 42 eicosanoids in a longitudinal study of 95 PWH and 25 demographically comparable uninfected participants. Routine clinical chemistry, virologic, immune markers, and a neuropsychological test battery assessing 7 cognitive domains were administered to all participants at 2 study visits over an average of 6.5 months.ResultsPlasma eicosanoid concentrations were elevated in PWH (n = 95) compared with seronegative controls (n = 25) (100% prediction power at 5% false discovery rate [FDR], α = 0.0531) and were negatively associated with lower current and nadir CD4 lymphocyte counts. Higher levels of eicosanoids were associated with impairments in working memory, verbal fluency, and executive function. Higher plasma viral load was associated with elevated proinflammatory eicosanoids (24% prediction power at 5% FDR and 42.4% prediction power at 10% FDR, α = 0.10). Longitudinal analyses showed that eicosanoid levels were correlated with viral load and with plasma creatinine. Despite associations of eicosanoids with viral loads, elevated plasma eicosanoids were similar in virally suppressed and not fully suppressed PWH.DiscussionThese data show that HIV infection is associated with a robust production of eicosanoids that are not substantially reduced by antiretroviral therapy (ART). The sustained elevation of these oxylipins in PWH despite ART may contribute to an accelerated aging phenotype that includes earlier than expected brain and peripheral organ damage.

Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness

Schizophrenia and bipolar disorder are severe mental illnesses (SMI) linked to both genetic and environmental factors. Herpes simplex virus 1 (HSV1) is a common neurotropic pathogen which after the primary infection establishes latency with periodic reactivations. We hypothesized that the latent HSV1 infection is associated with brain structural abnormalities and cognitive impairment, especially in SMI. We included 420 adult patients with SMI (schizophrenia or bipolar spectrum) and 481 healthy controls. Circulating HSV1 immunoglobulin G concentrations were measured with immunoassays. We measured the total grey matter volume (TGMV), cortical, subcortical, cerebellar and regional cortical volumes based on T1-weighted MRI scans processed in FreeSurfer v6.0.0. Intelligence quotient (IQ) was assessed with the Wechsler Abbreviated Scale of Intelligence. Seropositive patients had significantly smaller TGMV than seronegative patients (642 cm3 and 654 cm3, respectively; p = 0.019) and lower IQ (104 and 107, respectively; p = 0.018). No TGMV or IQ differences were found between seropositive and seronegative healthy controls. Post-hoc analysis showed that (a) in both schizophrenia and bipolar spectrum, seropositive patients had similarly smaller TGMV than seronegative patients, whereas the HSV1-IQ association was driven by the schizophrenia spectrum group, and (b) among all patients, seropositivity was associated with smaller total cortical (p = 0.016), but not subcortical or cerebellar grey matter volumes, and with smaller left caudal middle frontal, precentral, lingual, middle temporal and banks of superior temporal sulcus regional cortical grey matter volumes. The results of this cross-sectional study indicate that HSV1 may be an environmental factor associated with brain structural abnormalities and cognitive impairment in SMI.

Evaluation of Sensitivity and Specificity of High Fluorescence Lymphocyte Count Percentage of Sysmex XN Analyzer in Diagnosis of Dengue

BACKGROUND: The Sysmex XN-series hematology analyzers provide newer parameters including high fluorescence lymphocyte cell percentage (HFLC%) which correlates with the presence of atypical lymphocytes in peripheral blood. We aimed to analyze the sensitivity and specificity of HFLC% as a diagnostic tool and its association with serological status in diagnosed dengue patients and thereby establish a cutoff of HFLC% based on serology. Besides, we also wish to correlate HFLC% with thrombocytopenia in these patients. MATERIALS AND METHODS: A total of 1500 serum samples were subjected to serological evaluation for dengue. After excluding hematological malignancies and autoimmune disorders, the same day complete blood count parameters including HFLC% and platelet counts were collected retrospectively for 292 serologically positive dengue cases and 76 seronegative controls. RESULTS: Our result shows that in nonstructural 1 antigen-positive cases, a cutoff of &gt;5.2% HFLC can have a sensitivity of 79.5% and specificity of 98.6%. We found a different cut off of HFLC% &gt;3.2% (sensitivity 83.4%, specificity 98.6%) for the cases with only immunoglobulin M positivity and a cut off of HFLC% &gt;2.6% (sensitivity 86.1%, specificity 96%) in the dual positive cases (immunoglobulin M with nonstructural 1 antigen). Besides, high HFLC% also shows a strong correlation with platelet count with a Spearman correlation coefficient of −0.6. CONCLUSIONS: The result of our study shows that a specific cutoff of HFLC% can not only help us to suspect dengue fever but also predict the risk of thrombocytopenia in already diagnosed dengue patients. The sensitivity and specificity of HFLC% varied with the serological status of the patients which depend on the days of fever on presentation.

Antibody response to SARS-CoV-2 vaccines among hospitalized patients in China: a case-control study

ABSTRACT A lack of confidence on the vaccination drive hinders the management of the COVID-19 pandemic. We aimed to assess the antibody response to the SARS-CoV-2 vaccine among hospitalized patients in China. This case-control study was based on SARS-CoV-2 sero-surveillance during hospitalization. From April to June 2021, hospitalized patients without documented COVID-19 infection from the Department of Urology were routinely assayed for anti-SARS-CoV-2 antibodies. The SARS-CoV-2 vaccination history of each participant was obtained from their vaccination records. Of the 405 participants, there were 37 seropositive participants (case group) and 368 seronegative participants (control group); 68 participants (16.8%) had received the inactivated SARS-CoV-2 vaccine, including 54 who received the Sinovac-CoronaVac vaccine and 14 received the Sinopharm vaccine. All seropositive participants who had received one or two doses of the SARS-CoV-2 vaccine were assessed for at least 16 days, while 31 (8.4%) of 368 seronegative controls who had received the vaccine were tested for 1–94 days. The overall seroconversion rate was 54.4% (37/68) in the vaccinated participants who received the inactivated SARS-CoV-2 vaccine. The odds ratio (OR) and confidence interval (CI) for seropositivity was 6.20 (95% CI: 2.05–18.71) in those received full vaccination with two doses versus those partially vaccinated participants with one dose after adjusting for sex and age. These findings imply that the inactivated SARS-CoV-2 vaccine could have a protective antibody response.

Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy.

Background: HIV infection results in immunometabolic reprogramming. While we are beginning to understand how this metabolic reprogramming regulates the immune response to HIV infection, we do not currently understand the impact of ART on immunometabolism in people with HIV (PWH). Methods: Serum obtained from HIV-infected (n = 278) and geographically matched HIV seronegative control subjects (n = 300) from Rakai Uganda were used in this study. Serum was obtained before and ~2 years following the initiation of ART from HIV-infected individuals. We conducted metabolomics profiling of the serum and focused our analysis on metabolic substrates and pathways assocaited with immunometabolism. Results: HIV infection was associated with metabolic adaptations that implicated hyperactive glycolysis, enhanced formation of lactate, increased activity of the pentose phosphate pathway (PPP), decreased β-oxidation of long-chain fatty acids, increased utilization of medium-chain fatty acids, and enhanced amino acid catabolism. Following ART, serum levels of ketone bodies, carnitine, and amino acid metabolism were normalized, however glycolysis, PPP, lactate production, and β-oxidation of long-chain fatty acids remained abnormal. Conclusion: Our findings suggest that HIV infection is associated with an increased immunometabolic demand that is satisfied through the utilization of alternative energetic substrates, including fatty acids and amino acids. ART alone was insufficient to completely restore this metabolic reprogramming to HIV infection, suggesting that a sustained impairment of immunometabolism may contribute to chronic immune activation and comorbid conditions in virally suppressed PWH.

LRP4-IgG service line testing in seronegative myasthenia gravis and controls

BackgroundLRP4 is a post-synaptic membrane protein that promotes acetylcholine (AChR) clustering on the crest of post-synaptic neuromuscular folds. Autoantibodies against LRP4 are suggested to account for myasthenia gravis (MG) patients negative for antibodies to AChR. ObjectivesTo report a clinical experience with service-line LRP4-IgG cell-based testing in electrodiagnostically confirmed MG patients and controls. MethodsWe identified all Mayo patients undergoing MG evaluations with send out LRP4-IgG antibody testing by cell-based assay, having clinical-electrodiagnostic (EDX) testing. To be included, muscle acetylcholine receptor binding (AChR-Bi) and muscle-specific tyrosine kinase (MuSK) antibodies had to be absent prior to LRP4-IgG testing. Follow-up AChR-Bi antibody testing was reviewed. Also tested for LRP4-IgGs were 119 healthy subjects. ResultsIdentified were 25 generalized MG, 24 ocular MG, and 55 patients initially considered to have MG prior to negative EDX testing. No seronegative patients with EDX confirmed MG had LRP4-IgG positivity but five non-MG patients did: Guillain-Barre syndrome with fatigue (N = 1); multiple cranial neuropathies (N = 1); functional neurologic disorders (N = 3). Of healthy subjects, 4% (5/119) were LRP4-IgG positive (N = 5) or had a borderline result (N = 1). Of MG patients with repeat AChR-Bi testing, 40% (10/25) seroconverted (5 with ocular MG and 5 with generalized MG) (median AChR IgG value: 0.34 nmol/L, range 0.2–20.9 nmol/L, median followup 26 months, range 2–72 months). ConclusionClinical review of LRP4-IgG commercial cell-based testing suggests lack of diagnostic utility in seronegative EDX-confirmed MG. The clinical utility of LRP4-IgG testing is not substantiated in service line testing. In contrast, repeat testing for AChR-Bi antibodies is shown clinically useful.

Association between feline immunodeficiency virus and Leishmania infantum infections in cats: a retrospective matched case-control study

BackgroundFeline leishmaniosis caused by Leishmania infantum is often associated with feline immunodeficiency virus (FIV) infection; however, the role and clinical significance of this coinfection remain unknown. This study aimed to assess whether FIV is associated with L. infantum infection in cats from canine leishmaniosis endemic areas and to report the clinical signs and hematological alterations associated with coinfection.MethodsA retrospective matched case-control study (ratio 1:2) was conducted. Data of clinical examination and complete blood count (CBC) were selected from a cohort of 705 cats examined for epidemiological studies on feline leishmaniosis conducted between 2012 and 2019. Ninety-one FIV seropositive cases and 182 FIV seronegative control cats were selected. Matching was done according to age, sex, lifestyle and geographic provenience of case cats. Rapid ELISA devices were mainly used to detect anti-FIV antibodies. Anti-Leishmania IgG antibodies were detected by indirect-immunofluorescence test (IFAT). Leishmania DNA was searched in blood, oral and conjunctival swabs by quantitative real-time PCR.ResultsFeline immunodeficiency virus seropositive cats had no hematological abnormalities suggestive of an advanced stage of FIV infection and were statistically more frequently IFAT positive, and their risk of being L. infantum antibody positive was 2.8 greater than in the FIV seronegatives. The association of FIV seropositivity with L. infantum antibody positivity was confirmed in the univariable model of logistic regression. A multivariate model found FIV infection and L. infantum PCR positivity as predictors of a positive L. infantum IFAT result. Male outdoor cats from rural or suburban areas were at risk for FIV and L. infantum antibody positivity. Clinical signs more frequently associated with the coinfection were oral lesions, pale mucous membranes and low body condition score (BCS).ConclusionsThis study documents that FIV seropositive cats with no hematological abnormalities suggestive of an advanced stage of FIV infection are more prone to be L. infantum seroreactive by IFAT in endemic areas. Therefore, FIV seropositive cats should be tested for L. infantum antibodies and treated for preventing sand fly bites. Pale mucous membranes, low BCS and oral lesions but no CBC abnormalities were significantly associated with the coinfection.Graphical abstract

People living with HIV have low trabecular bone mineral density, high bone marrow adiposity, and poor trabecular bone microarchitecture at the proximal femur.

People living with HIV (PLWH) have increased risk of osteoporosis and fractures. However, studies assessing the main determinants of bone strength in the proximal femur exclude this vulnerable population. We assessed the proximal femur of 40 PLWH and 26 age-matched seronegative controls using quantitative computed tomography and magnetic resonance imaging. We examined cortical volumetric bone mineral density (Ct.vBMD), trabecular vBMD (Tb.vBMD), cortical thickness (Ct.Th), bone marrow adiposity (BMA), and trabecular number, separation, and bone volume fraction. Parametric comparisons between the two groups were made for the femoral head, femoral neck, trochanter, and total hip using linear regression adjusting for several covariates, including metrics of body composition. In addition, we investigated the associations of BMA with Tb.vBMD and trabecular microarchitecture with Spearman's rank partial correlations. PLWH had lower Tb.vBMD and deteriorated trabecular microarchitecture in the femoral neck, trochanter and total hip, and elevated BMA in the femoral head, femoral neck, and total hip. Ct.vBMD and Ct.Th were not significantly different between the two groups. BMA was significantly associated with lower Tb.vBMD and deteriorated trabecular microarchitecture in both groups albeit at different femoral regions. Our findings suggest that the trabecular, and not the cortical, compartment is compromised in the proximal femur of PLWH. The observed impairments in fracture-prone regions in PLWH indicate lower femoral strength and suggest higher fracture risk. The inverse associations of BMA with trabecular bone density and microarchitecture quality agree with findings at other anatomic sites and in other populations, suggesting that excess BMA possibly due to a switch from the osteoblast to the adipocyte lineage may be implicated in the pathogenesis of bone fragility at the femur in PLWH.

Pulmonary Function and Long-Term Respiratory Symptoms in Children and Adolescents After COVID-19.

BackgroundPersistent respiratory symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults are frequent, and there can be long-term impairment of pulmonary function. To date, only preliminary evidence is available on persistent respiratory sequelae of SARS-CoV-2 in children and adolescents. Our objective was to examine the long-term effects of symptomatic and asymptomatic SARS-CoV-2 infections on pulmonary function in this age group in a single-center, controlled, prospective study.MethodsParticipants with serological or polymerase chain reaction-based evidence of SARS-CoV-2 infection were recruited from a population-based study of seroconversion rates. Multiple-breath washout (MBW), body plethysmography, and diffusion capacity testing were performed for children and adolescents. Participants were interviewed about their symptoms during the acute phase of infection and long-lasting symptoms. Cases were compared with SARS-CoV-2 seronegative controls from the same population-based study with and without history of respiratory infection within 6 months prior to assessment. Primary endpoints were differences in pulmonary function, including diffusion capacity and MBW, between participants with and without evidence of SARS-CoV-2 infection. Secondary endpoints included correlation between lung function and long-lasting symptoms as well as disease severity.FindingsIn total, 73 seropositive children and adolescents (5–18 years) were recruited after an average of 2.6 months (range 0.4–6.0) following SARS-CoV-2 infection. Among 19 patients (27.1%) who complained of persistent or newly emerged symptoms since SARS-CoV-2, 8 (11.4%) reported respiratory symptoms. No significant differences were detected in frequency of abnormal pulmonary function when comparing cases with 45 controls, including 14 (31.1%) with a history of previous infection (SARS-CoV-2: 12, 16.4%; controls: 12, 27.7%; odds ratio 0.54, 95% confidence interval 0.22–1.34). Only two patients with persistent respiratory symptoms showed abnormal pulmonary function. Multivariate analysis revealed reduced forced vital capacity (p = 0.012) in patients with severe SARS-CoV-2 infection.InterpretationPulmonary function is rarely impaired in children and adolescents after SARS-CoV-2 infection, except from those with severe infection, and did not differ between SARS-CoV-2 and other previous infections, suggesting that SARS-CoV-2 is not more likely to cause pulmonary sequelae than other infections. The discrepancy between persisting respiratory symptoms and normal pulmonary function suggests a different underlying pathology such as dysfunctional breathing.

Coagulation Parameters in Human Immunodeficiency Virus Infected Patients: A Systematic Review and Meta-Analysis

Background Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the mortality of HIV but increased coagulopathies. HIV-related thrombocytopenia, prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), and high D-dimer level commonly manifested in patients with HIV. Thus, this study is aimed to compare coagulation parameters of HAART-treated and HAART-naïve HIV-infected patients with HIV-seronegative controls. Methods A systematic literature search was conducted using the databases PubMed/MEDLINE, Embase, Web of Science, and Google Scholar of studies published until July 2021. The primary outcome of interest was determining the pooled mean difference of coagulation parameters between HIV-infected patients and seronegative controls. The Joana Briggs Institute (JBI) critical appraisal tool was used for quality appraisal. Statistical analyses were performed using Stata11.0 software. The statistical results were expressed as the effect measured by standardized mean difference (SMD) with their related 95% confidence interval (CI). Results A total of 7,498 participants (1,144 HAART-naïve patients and 2,270 HAART-treated HIV-infected patients and 3,584 HIV-seronegative controls) from 18 studies were included. HIV-infected patients (both on HAART and HAART-naive) exhibited significantly higher levels of PT than HIV-seronegative controls (SMD = 0.66; 95% CI: 0.53–0.80 and SMD = 1.13; 95% CI: 0.60–2.0, respectively). The value of APTT was significantly higher in patients with HIV on HAART than in seronegative controls. However, the values of PLT count, APTT, and fibrinogen level were significantly higher in seronegative controls. Besides, the level of fibrinogen was significantly higher in HAART-treated than treatment-naïve patients (SMD = 0.32; 95%CI: 0.08, 0.57). Moreover, the level of APTT and PT had no statistical difference between HAART and HAART-naïve HIV-infected patients. Conclusions This study identified that HIV-infected patients are more likely to develop coagulation abnormalities than HIV-seronegative controls. Therefore, coagulation parameters should be assessed regularly to prevent and monitor coagulation disorders in HIV-infected patients.

Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition - A Nested Case-Control Study in HIV-1 Serodiscordant Couples.

Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence includes macaque studies which suggest that xenoimmunization with HLA antigens may protect against simian immunodeficiency virus infection. Since HIV gp120 shows homology with class 2 HLA, including shared affinity for binding to CD4, class 2 HLA antibodies may influence HIV acquisition via binding to gp120 on the viral envelope. We conducted a nested case-control study on HIV serodiscordant couples, comparing the frequency of HLA antibodies among highly exposed persistently seronegative controls with those who went on to acquire HIV (HIV-seroconverters). We first performed low resolution HLA typing on 143 individuals who were HIV-infected at enrollment (index partners) and their corresponding sexual partners (115 highly exposed persistently seronegative individuals and 28 HIV-seroconverters). We then measured HLA class 1 and 2 antibodies in the highly exposed persistently seronegative individuals and HIV-seroconverters at early and late timepoints. We analyzed whether such antibodies were directed at HLA specificities of their HIV-infected index partners, and whether autoantibodies or complement-fixing class 2 HLA antibodies were present. Seventy-nine percent of highly exposed persistently seronegative individuals had HLA antibodies; 56% against class 1 and 50% against class 2 alleles. Half of the group of highly exposed persistently seronegative individuals, prior to seroconversion, expressed class 2 HLA antibodies, compared with only 29% of controls (p=0.05). HIV infection was a sensitizing event leading to de novo development of antibodies against HLA-A and HLA-B loci, but not against class 2 loci. HLA autoantibodies were present in 27% of highly exposed persistently seronegative individuals. Complement-fixing class 2 HLA antibodies did not differ significantly between highly exposed persistently seronegative individuals and seroconverters. In multivariable regression, presence of class 2 HLA antibodies at early timepoints was associated with reduced odds of HIV acquisition (odds ratio 0.330, confidence interval 0.112-0.976, p=0.045). These epidemiological data suggest that pre-existing class 2 HLA antibodies were associated with reduced odds of HIV acquisition.

Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

BackgroundFatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis and damaging the endothelium, we investigated endothelial dysfunction (ED) and endothelial biomarkers in patients with PCS.MethodsWe studied the endothelial function in 30 PCS patients with persistent fatigue and exertion intolerance as well as in 15 age- and sex matched seronegative healthy controls (HCs). 14 patients fulfilled the diagnostic criteria for ME/CFS. The other patients were considered to have PCS. Peripheral endothelial function was assessed by the reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) in patients and HCs. In a larger cohort of patients and HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) and ACE2 were analysed as endothelial biomarkers.ResultsFive of the 14 post-COVID ME/CFS patients and five of the 16 PCS patients showed ED defined by a diminished RHI (< 1.67), but none of HCs exhibited this finding. A paradoxical positive correlation of RHI with age, blood pressure and BMI was found in PCS but not ME/CFS patients. The ET-1 concentration was significantly elevated in both ME/CFS and PCS patients compared to HCs and PCHCs. The serum Ang-2 concentration was lower in both PCS patients and PCHCs compared to HCs.ConclusionA subset of PCS patients display evidence for ED shown by a diminished RHI and altered endothelial biomarkers. Different associations of the RHI with clinical parameters as well as varying biomarker profiles may suggest distinct pathomechanisms among patient subgroups.

Serum protein concentration and amino acid profile of HIV/HBV co-infected subjects on HAART in Plateau State, Nigeria.

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are currently two important blood-borne human pathogens of major public health concern with high prevalence rates in Africa. The study assessed the impact of HIV and HBV mono- and co-infections on serum total protein, albumin, globulin fractions and plasma free amino acids concentrations. This was a cross-sectional study on adult (25 - 64 years old) patients on Highly Active Antiretroviral Therapy attending AIDS Preventive Initiative in Nigeria Centre, Jos University Teaching Hospital, Plateau State, Nigeria. It involved 80 subjects; 20 HIV/HBV co-infected, 20 each of HIV and HBV mono-infected controls, and 20 seronegative controls. Significant (p<0.05) increases in total protein and gamma globulin but a reduction in albumin concentrations were observed in the HIV/HBV co-infected group. Similarly, significant (p<0.05) increases in alpha-1 and alpha-2 globulin concentrations were observed in the mono- and co-infected groups compared to the seronegative control group. There were significant (p<0.05) increases in the glucogenic, aromatic and branched-chain amino acid concentrations of the HIV/HBV co-infected subjects. The study suggests prognostic importance of alpha and gamma globulin fractions of serum protein as well as amino acid profile in the management of HIV/HBV co-infection.

A point-of-care diagnostic test for aquaporin-4 antibody seropositive neuromyelitis optica

BackgroundGiven the need for specialized laboratory techniques, diagnostic testing for serum antibodies to aquaporin-4, a protein associated with neuromyelitis optica spectrum disorder (NMOSD), is not globally accessible. We aimed to evaluate a novel point-of-care, filter paper-based test for serum AQP4 antibodies (AQP4-Ab). MethodsAdults with AQP4-Ab seropositive NMOSD and seronegative controls (with other central nervous system demyelinating diagnoses) used lancets to place blood drops (∼1 mL) on filter paper cards. Samples were analyzed after an average of 9.4 days using transfected AQP4-GFP HEK293 cells, and results were compared to participants’ prior serum AQP4-Ab test results by blinded laboratory staff. ResultsOf 40 participants (mean age 53.7 years; 83% female), 25 were cases and 15 were controls. The most common diagnosis of controls was multiple sclerosis (73%). The average NMOSD disease duration was 6.3 years. All AQP4-Ab seropositive participants were on disease modifying therapies at the time of participation. The point-of-care test yielded a sensitivity of 80% and specificity of 93% (positive and negative predictive values 95% and 74%). ConclusionThis point-of-care AQP4-Ab testing method may become a pragmatic option to diagnose AQP4-Ab seropositive NMOSD in difficult-to-reach settings. This method should be confirmed with other testing parameters and field tested in new populations.

Cognitive screening in HTLV-1-infected people using a self-perceived memory score and auditory P300.

The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the most common neurological manifestation associated with human T-cell lymphotropic virus type-1 (HTLV-1) infection. Although cognitive impairment has been highlighted in the spectrum of HTLV-1 neurological manifestations, it may go unnoticed in those who do not spontaneously report it. We aimed at evaluating the applicability of a self-perceived memory score (SMS) and the cognitive event-related potential (P300) for early detection of cognitive impairment in HTLV-1-infected people. The SMS was measured by a 0-10 point numeric scale combined with a sad-happy face rating scale. The higher the number, the better was the SMS. The P300 was obtained through an oddball paradigm with a mental counting task. The participants were 15 (21.4%) individuals with HAM/TSP, 20 (28.6%) HTLV-1 asymptomatic carriers, and 35 (50%) seronegative controls. We found that SMS (p < 0.001) and P300 latency (p < 0.001) got progressively worse from the seronegative controls to the asymptomatic carriers and then to the HAM/TSP. The results that indicated cognitive impairment were SMS < 7.2 points and P300 latency > 369.0ms. The HAM/TSP group showed the highest prevalence of altered P300 (80%) and SMS (87%). Interestingly, the asymptomatic group also presented significantly higher prevalence of altered SMS (60%) and P300 (35%) when compared to controls (< 10%). The frequency of cognitive impairment was 16 times higher in the HTLV-1 asymptomatic group and 69 times higher in the HAM/TSP group when compared to controls. The use of SMS in the medical consultation was a useful and easy-to-apply method to screen HTLV-1-infected subjects for everyday memory complaints.

Cytomegalovirus Seropositivity as a Potential Risk Factor for Increased Noise Trauma Susceptibility.

Context:Cytomegalovirus (CMV) represents the leading congenital viral infection in humans. Although congenital CMV due to vertically transmitted infections is the main cause of CMV-related diseases, adult CMV infections might still be of clinical significance. It is still discussed how far CMV seropositivity, due to horizontal infection in immunocompetent adults, is able to induce significant dysfunction. The present study investigates in how far CMV seropositivity is an additional risk factor for an increasing susceptibility to sensorineural hearing loss induced by acoustic injury during adulthood in a guinea pig CMV (GPCMV) model of noise-induced hearing loss (NIHL).Methods:Two groups (GPCMV seropositive vs. seronegative) of normal hearing adult guinea pigs were exposed to a broadband noise (5–20 kHz) for 2 hours at 115 dB sound pressure level. Frequency-specific auditory brainstem response recordings for determination of auditory threshold shift were carried out and the number of missing outer hair cells was counted 2 weeks after the noise exposure.Results:The data show a slightly increased shift in auditory thresholds in seropositive animals compared to the seronegative control group in response to noise trauma. However, the observed difference was significant at least at high frequencies. The differences in threshold shift are not correlated with outer hair cell loss between the experimental groups.Conclusion:The results point to potential additional pathologies in a guinea pig NIHL model in correlation to GPCMV seropositivity, which should be taken into account when assessing risks of latent/reactivated CMV infection. Due to the relatively slight effect in the present data, the aim of future studies should be a more detailed consideration (e.g., larger sample size) and to localize possible target structures as well as the significance of the infection route.

The role of Serum Interleukin-4 and Interleukin-6 in Helicobacter pylori-infected patients

BackgroundHelicobacter pylori (H. pylori) is a Gram-negative bacteria that colonizes the gastrointestinal mucosa and causes chronic inflammation. AimsThere are several studies related to cytokines concentrations in H. pylori infection, but there is no study that clarifies the role of IL-4 and IL-6 together in H. pylori infection. Subjectsand methods: A total of (65) individuals, (25) healthy controls and (40) patients with H. pylori infection which are submitted to the hepato-gastrointestinal unit of AL-Imamian Al-Kadhimiyain medical hospital city in Baghdad consulted and diagnosed by traditional ways. In addition, the diagnosis was confirmed by ELISA Helicobacter pylori IgG kit. IL-4 and IL-6 levels were also assessed by using ELISA kits, according to the manufactures procedures. ResultsSignificant increase of IL-4 and IL-6 concentration in seropositive patients compared with seronegative controls. ConclusionOur findings and previous researches indicate that the immune response of gastric mucosa to H. pylori varies among patients. It depends on the stage of infection, and increases the cytokines secretion in the chronic stage, which is expected because of increased immune cell infiltration at the site of infection.