Median Antibody Levels Research Articles

SARS-CoV-2 Antibody Response After a Third Dose of the BNT162b2 Vaccine in Patients Receiving Maintenance Hemodialysis or Peritoneal Dialysis

Rationale & ObjectiveRecent studies showed that antibody titers after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the dialysis population are diminished as compared with the general population, suggesting the possible value of a third booster dose. We characterized the humoral response after 3 doses of the BNT162b2 vaccine in patients treated with either maintenance hemodialysis (HD) or peritoneal dialysis (PD).Study DesignCase series.Setting & Participants69 French patients (38 HD and 31 PD) treated at a single center who received 3 doses of the BNT162b2 vaccine.FindingsHumoral response was evaluated using plasma levels of anti-SARS-CoV-2 spike protein S1 immunoglobulin measured after the second dose and at least 3 weeks after the third dose of the BNT162b2 vaccine. Patients (median age 68 years [interquartile range (IQR), 53-76 years], 65% men) had a median anti-S1 antibody level of 284 [IQR, 83-1190] AU/mL after the second dose, and 7,554 [IQR, 2,268-11,736] AU/mL after the third dose. Three patients were nonresponders (anti-S1 antibody level < 0.8 AU/mL), and 12 were weak responders (anti-S1 antibody level 0.8-50 AU/mL) after the second vaccine dose. After the third dose, 1 of the 3 initial nonresponders produced anti-spike antibody, and all the 12 initial weak responders increased their antibody levels. Patients with a greater increase in anti-S1 antibody levels after a third dose had lower antibody levels after the second dose, and a longer time interval between the second and the third dose. Adverse events did not seem to be more common or severe after a third vaccine dose.LimitationsObservational study, small sample size. Relationship between antibody levels and clinical outcomes is not well understood.ConclusionsA third dose of the BNT162b2 vaccine substantially increased antibody levels in patients receiving maintenance dialysis and appeared to be as well tolerated as a second dose.

Evaluation of the SARS-CoV-2 Antibody Response to the BNT162b2 Vaccine in Patients Undergoing Hemodialysis

Patients undergoing hemodialysis have a high mortality rate associated with COVID-19, and this patient population often has a poor response to vaccinations. Randomized clinical trials for COVID-19 vaccines included few patients with kidney disease; therefore, vaccine immunogenicity is uncertain in this population. To evaluate the SARS-CoV-2 antibody response in patients undergoing chronic hemodialysis following 1 vs 2 doses of BNT162b2 COVID-19 vaccination compared with health care workers serving as controls and convalescent serum. A prospective, single-center cohort study was conducted between February 2 and April 17, 2021, in Toronto, Ontario, Canada. Participants included 142 patients receiving in-center hemodialysis and 35 health care worker controls. BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. SARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP). Among the 142 participants undergoing maintenance hemodialysis, 94 (66%) were men; median age was 72 (interquartile range, 62-79) years. SARS-CoV-2 IgG antibodies were measured in 66 patients receiving 1 vaccine dose following a public health policy change, 76 patients receiving 2 vaccine doses, and 35 health care workers receiving 2 vaccine doses. Detectable anti-NP suggestive of natural SARS-CoV-2 infection was detected in 15 of 142 (11%) patients at baseline, and only 3 patients had prior COVID-19 confirmed by reverse transcriptase polymerase chain reaction testing. Two additional patients contracted COVID-19 after receiving 2 doses of vaccine. In 66 patients receiving a single BNT162b2 dose, seroconversion occurred in 53 (80%) for anti-spike and 36 (55%) for anti-RBD by 28 days postdose, but a robust response, defined by reaching the median levels of antibodies in convalescent serum from COVID-19 survivors, was noted in only 15 patients (23%) for anti-spike and 4 (6%) for anti-RBD in convalescent serum from COVID-19 survivors. In patients receiving 2 doses of BNT162b2 vaccine, seroconversion occurred in 69 of 72 (96%) for anti-spike and 63 of 72 (88%) for anti-RBD by 2 weeks following the second dose and median convalescent serum levels were reached in 52 of 72 patients (72%) for anti-spike and 43 of 72 (60%) for anti-RBD. In contrast, all 35 health care workers exceeded the median level of anti-spike and anti-RBD found in convalescent serum 2 to 4 weeks after the second dose. This study suggests poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in the hemodialysis population, supporting adherence to recommended vaccination schedules and avoiding delay of the second dose in these at-risk individuals.

One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms.

After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including headache, concentration difficulties and loss of smell/taste, were reported by 51 of 83 (61%) participants and decreased over time to 28% one year after COVID-19. Specific IgA and IgG antibodies were detectable in 78% and 66% of participants, respectively, at a 12-month follow-up. Median antibody levels decreased by approximately 50% within the first 6 months but remained stable up to 12 months. Neutralizing antibodies could be found in 50% of participants; specific INFgamma-producing T-cells were present in two thirds one year after COVID-19. Activation-induced marker assays identified specific T-helper cells and central memory T-cells in 80% of participants at a 12-month follow-up. In correlative analyses, older age and a longer duration of the acute phase of COVID-19 were associated with higher humoral and T-cell responses. A weak correlation between long-term loss of taste/smell and low IgA levels was found at early time points. These data indicate a long-lasting immunological memory against SARS-CoV-2 after mild COVID-19.

Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis

Assessing the evolution of SARS-CoV-2 immune response among patients receiving dialysis can define its durability in a highly clinically relevant context because patients receiving dialysis share the characteristics of persons most susceptible to SARS-CoV-2 infection. To evaluate the persistence of SARS-CoV-2 receptor-binding domain (RBD) IgG in seroprevalent patients receiving dialysis. Prospective. Nationwide sample from dialysis facilities. 2215 patients receiving dialysis who had evidence of SARS-CoV-2 infection as of July 2020. Remainder plasma from routine monthly laboratories was used to measure semiquantitative RBD IgG index value over 6 months. A total of 2063 (93%) seroprevalent patients reached an assay detectable response (IgG index value ≥1). Most (n = 1323, 60%) had responses in July with index values classified as high (IgG ≥10); 1003 (76%) remained within this stratum. Adjusted median index values declined slowly but continuously (July vs. December values were 21 vs. 13; P < 0.001). The trajectory of the response did not vary by age group, sex, race/ethnicity, or diabetes status. Patients without an assay detectable response (n = 137) were more likely to be White and in the younger (18 to 44 years) or older (≥80 years) age groups and less likely to have diabetes and hypoalbuminemia. Lack of data on symptoms or reverse transcriptase polymerase chain reaction diagnosis, cohort of persons who survived infection, and use of a semiquantitative assay. Despite impaired immunity, most seropositive patients receiving dialysis maintained RBD antibody levels over 6 months. A slow and continual decline in median antibody levels over time was seen, but no indication that subgroups with impaired immunity had a shorter-lived humoral response was found. Ascend Clinical Laboratories.

Periodontal P eriodontal Parameters and Anti-Car ameters and Anti-Cardiolipin Antibodies F diolipin Antibodies Following ollowing Periodontal Ther eriodontal Therapy in Chr y in Chronic Periodontitis eriodontitis

Anti-cardiolipin (anti-CL) antibodies are autoantibodies which are directed against cell membrane phospholipids. A significant number of periodontitis patients showed positive for anti-CL antibody. Objective: This study aimed to determine the periodontal parameters and anti-CL antibodies levels before and after non-surgical periodontal therapy in chronic periodontitis. Methods: This cross-sectional study had been carried out at Periodontal Clinic, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. Thirty five chronic periodontitis (CP) and 39 non-periodontitis (NP) patients underwent clinical periodontal examination at baseline. Plaque index (PI), gingival index (GI), periodontal pocket depth (PPD), and clinical attachment loss (CAL) were measured. Scaling and polishing was performed and blood samples were taken for IgG and IgM anti-CL antibodies analysis. Re-evaluation was performed four weeks after initial therapy. CP patients were re-examined, all periodontal parameters were recorded and blood samples were taken for reassessment of IgG and IgM anti-CL antibodies. Results: Significant difference means of PI (p=0.001), GI (p=0.000), PPD (p=0.000) and, CAL (p=0.000) were found between CP and NP groups. All periodontal parameters were significantly reduced (p≤0.05) after four weeks of therapy. The mean levels of IgG and IgM anti-CL antibodies at baseline were significantly higher in CP than NP group (IgG=4.46 vs 3.22, p=0.002; IgM=3.28 vs 2.57, p=0.019). No significant difference of the median levels of IgG (p=0.82) and IgM anti-CL antibodies (p=0.35) following therapy. Conclusion: All periodontal parameters were significantly reduced following periodontal therapy. Higher level of Anti-CL antibodies in CP indicates stimulation of autoantibodies production by periodontal infection. Nonetheless no significant changes of this anti-CL antibodies levels despite significant reduction of the clinical parameters after periodontal therapy

Immunoglobin G/total antibody testing for SARS-CoV-2: A prospective cohort study of ambulatory patients and health care workers in two Belgian oncology units comparing three commercial tests

BackgroundCoronavirus disease (COVID-19) is interfering heavily with the screening, diagnosis and treatment of cancer patients. Better knowledge of the seroprevalence and immune response after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in this population is important to manage them safely during the pandemic. Methods922 cancer patients, 100 non-cancer patients and 94 health care workers (HCW) attending the Multidisciplinary Oncology Unit of Antwerp University Hospital from 24th of March 2020 till 31st of May 2020, and the Oncology Unit of AZ Maria Middelares Hospital, Ghent, from 13th of April 2020 till 31st of May 2020 participated in the study. The Alinity® (A; Abbott) and Liaison® (D; DiaSorin) commercially available assays were used to measure SARS-CoV-2 IgG, while total SARS-CoV-2 Ig was measured by Elecsys® (R; Roche). ResultsIn the overall study population IgG/total SARS-CoV-2 antibodies were found in respectively 32/998 (3.2%), 68/1020 (6.7%), 37/1010 (3.7%) and of individuals using the A, D or R test. Forty-six out of 618 (7.4%) persons had a positive SARS-CoV-2 polymerase chain reaction (RT-PCR) test. Seroprevalence in cancer patients (A:2.2%, D:6.2%, R:3.0%), did not significantly differ from that in non-cancer patients (A:1.1%, D:5.6%, R:0.0%), but was lower than the HCW (A:13%, D:12%, R:12%; respectively Fisher’s exact test p = 0.00001, p = 0.046, p = 0.0004). A positive SARS-CoV-2 RT-PCR was found in 6.8% of the cancer patients, 2.3% of the non-cancer patients and 28.1% of the HCW (Fisher’s exact test p = 0.0004). Correlation between absolute values of the different Ig tests was poor in the cancer population. Dichotomising a positive versus negative test result, the A and R test correlated well (kappa 0.82 p McNemar test = 0.344), while A and D and R and D did not (respectively kappa 0.49 and 0.57; result significantly different p McNemar test = <0.0001 for both). The rate of seroconversion (>75%) and median absolute antibody levels (A: 7.0 versus 4.7; D 74.0 versus 26.6, R: 16.34 versus 7.32; all >P Mann Whitney U test = 0.28) in cancer patients and HCW with a positive RT-PCR at least 7 days earlier did not show any differences. However, none (N = 0/4) of the patients with hematological tumours had seroconversion and absolute antibody levels remained much lower compared to patients with solid tumours (R: 0.1 versus 37.6, p 0.003; D 4.1 versus 158, p 0.008) or HCW (all p < 0.0001). ConclusionHCW were at high risk of being infected by SARS-CoV-2 during the first wave of the pandemic. Seroprevalence in cancer patients was low in the study period. Although Ig immune response in cancer patients with solid tumours does not differ from healthy volunteers, patients with hematological tumours have a very poor humoral immune response. This has to be taken into account in future vaccination programmes in this population. SARS-CoV-2 antibody tests have divergent results and seem to have little added value in the management of cancer patients.

Effect of 4 years of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou, Mali

BackgroundMore than 200 million people live in areas of highly seasonal malaria transmission where Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was recommended in 2012 by WHO. This strategy is now implemented widely and protected more than 19 million children in 2018. It was previously reported that exposure to SMC reduced antibody levels to AMA1, MSP-142 and CSP, but the duration of exposure to SMC up to three 3 years, had no effect on antibody levels to MSP-142 and CSP.MethodsIn 2017, a cross-sectional survey was carried out 1 month after the last dose of SMC had been given to children aged 4–5 years randomly selected from areas where SMC had been given for 2 or 4 years during the malaria transmission season. A total of 461 children were enrolled, 242 children in areas where SMC had been implemented for 4 years and 219 children in areas where SMC had been implemented for 2 years. Antibody extracted from dry blood spots was used to measure IgG levels to the malaria antigens CSP, MSP-142 and AMA1 by ELISA.ResultsThe prevalence of antibodies to MSP-142 was similar in children who had received SMC for 4 years compared to those who had received SMC for only 2 years (85.1 vs 86.0%, ajusted odd ratio (aOR) = 1.06, 95% confidence intervals (CI 0.62–1.80), p = 0.80). The prevalence of antibodies to AMA-1 and to CSP was not lower in children who received SMC for 4 years compared to those who had received SMC for only 2 years (95.3 vs 88.8%, aOR = 3.16, 95% CI 1.44–6.95, p = 0.004 for AMA-1; and 91.2 vs 81.9%, aOR = 3.14, 95% CI 1.70–5.76, p < 0.001 for CSP). Median antibody levels for anti-MSP-142 IgG were not significatively inferior in children who had received SMC for four rather than 2 years (0.88 (IQR: 0.64–1.15) and 0.95 ((0.68–1.15), respectively), anti-CSP (1.30 (1.00–1.56) and 1.17 (0.87–1.47)), and anti-AMA-1 (1.45 (1.24–1.68) and 1.41 (1.17–1.64)).ConclusionIn an area of high seasonal malaria transmission, children who had received SMC for 4 years did not had lower seropositivity or antibody levels to AMA1, MSP-142 and CSP compared to children who had received SMC for only 2 years suggesting that children who have received SMC for 4 years may not be more at risk of malaria after the cessation of SMC than children who have received SMC for a shorter period.

Possible vertical transmission and antibodies against SARS-CoV-2 among infants born to mothers with COVID-19: A living systematic review.

Current evidence suggests that coronavirus disease 2019 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), is predominantly transmitted from human-to-human. However, evidence on vertical transmission and natural passive immunity among the newborns exposed to COVID-19 is scanty and varies. This poses a challenge on preventive interventions for the newborns. We conducted a systematic review to first, determine the likelihood of vertical transmission among COVID-19 exposed infants and second, determine whether antibodies against SARS-CoV-2 were generated among COVID-19 vertically exposed but negative infants. This review registered in PROSPERO searched evidence from PubMed/MEDLINE and Google Scholar, among others. About 517 studies were pooled, where 33 articles (5.8%) met the inclusion criteria such as infection prevention and control measures at birth. A total of 205 infants born to COVID-19 positive mothers were studied. Overall, 6.3% (13/205; 95% CI: 3.0%-9.7%) of the infants tested positive for COVID-19 virus at birth. Of 33 eligible studies, six studies (18.8%) reported about immunoglobulin G/M (IgG/IgM) against SARS-CoV-2. IgG/IgM were detected in 90% infants (10/11; 95% CI: 73.9%-107.9%) who tested negative for COVID-19 virus. The median antibody levels detected were 75.49 AU/ml (range, 7.25-140.32 AU/ml) and 3.79 AU/ml (range, 0.16-45.83 AU/ml), p = .0041 for IgG and IgM, respectively. In conclusion, the current evidence revealed a low possibility of vertical transmission of COVID-19 and antibodies against SARS-CoV-2 were detected among vertically exposed but negative infants. Further studies on transplacental transmission and the magnitude of natural passive immunity in infants born to mothers with COVID-19 are warranted.

Comparative Pertussis Antibody Response of Nigerian Children to Diphtheria, Pertussis, Tetanus (DPT) and Pentavalent Vaccines

Background: In Nigeria Pentavalent vaccine had replaced Diphtheria-Pertussis- Tetanus [DPT] vaccine in the prevention of pertussis since 2012. Aims and Objectives: The aim of this study was to compare the anti-pertussis immunoglobin G (IgG) response of children who received DPT with those who received the pentavalent vaccine. Subjects and Methods: This study was carried out in Akpabuyo LGA of Cross River State from April to June 2016. It was a cross-sectional survey of anti-pertussis IgG levels in children aged 6 months to 5 years who received DPT and those who received pentavalent vaccine. IgG antibody levels were determined using enzyme-linked immunosorbent assay. The protective level was set at >11 DU according to manufacturer’s cut off point. Results: Seventy eight out of 230 children [33.9%] who had received DPT had protective levels of anti-pertussis IgG compared to 74 out of 192 children [38.5%] who had received pentavalent vaccine. The difference was not statistically significant [p = 0.61]. The median IgG antibody level in those who received DPT was 8.0 DU (interquartile range (IQR) 4.0 - 13.0) compared with 9.0 DU (IQR) 4.0 - 15.0 in those who received pentavalent vaccine [p = 0.18]. No single factor investigated predicted the development of protective levels of antibody in the multivariate analysis. Conclusion/Recommendation: There was no difference in the antipertussis antibody response between DPT and pentavalent vaccines recipients. Further study is needed to elucidate factors that could be responsible for low anti-pertussis antibody response in this population.

Autoantibody levels are associated with acute kidney injury, anemia and post-discharge morbidity and mortality in Ugandan children with severe malaria

Autoantibodies targeting host antigens contribute to autoimmune disorders, frequently occur during and after infections and have been proposed to contribute to malaria-induced anemia. We measured anti-phosphatidylserine (PS) and anti-DNA antibody levels in 382 Ugandan children prospectively recruited in a study of severe malaria (SM). High antibody levels were defined as antibody levels greater than the mean plus 3 standard deviations of community children (CC). We observed increases in median levels of anti-PS and anti-DNA antibodies in children with SM compared to CC (p < 0.0001 for both). Children with severe malarial anemia were more likely to have high anti-PS antibodies than children with cerebral malaria (16.4% vs. 7.4%), p = 0.02. Increases in anti-PS and anti-DNA antibodies were associated with decreased hemoglobin (p < 0.05). A one-unit increase in anti-DNA antibodies was associated with a 2.99 (95% CI, 1.68, 5.31) increase odds of acute kidney injury (AKI) (p < 0.0001). Elevated anti-PS and anti-DNA antibodies were associated with post-discharge mortality (p = 0.031 and p = 0.042, respectively). Children with high anti-PS antibodies were more likely to have multiple hospital readmissions compared to children with normal anti-PS antibody levels (p < 0.05). SM is associated with increased autoantibodies against PS and DNA. Autoantibodies were associated with anemia, AKI, post-discharge mortality, and hospital readmission.

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test

BackgroundEarly signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk. MethodsA retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed. Corresponding clinical data were reviewed and patients with cystic fibrosis were assigned to one of four groups based on their mycobacterial culture results. In addition, anti-Mycobacterium avium complex immunoglobulin G levels were measured longitudinally before and after first positive culture in the period 1984–2015. ResultsThree-hundred and five patients with cystic fibrosis were included with a median of five nontuberculous mycobacterial cultures. Four individuals had Mycobacterium avium complex pulmonary disease at the time of cross sectional testing and their median antibody level was 22-fold higher than patients with no history of infection (1820 vs. 80 IgG units; p < 0.001). Test sensitivity was 100% (95% CI 40–100) and specificity 77% (95% CI 72–81). Longitudinal kinetics showed rising antibodies prior to first positive culture suggesting diagnostic delay. ConclusionsAntibody screening for Mycobacterium avium complex may be used as a supplement to culture. Although confirmation in a larger cohort is needed, our findings suggest that stratifying a cystic fibrosis population into high- and low-risk groups based on antibody levels may help clinicians identify patients in need of more frequent culture.

Long-term Antibody Response to Human Papillomavirus Vaccines: Up to 12 Years of Follow-up in the Finnish Maternity Cohort

Most cervical cancers are caused by vaccine-preventable infections with human papillomaviruses (HPV). The HPV prophylactic vaccines Gardasil and Cervarix have been widely used for >10 years and are reported to induce high antibody levels. A head-to-head comparison of the antibody responses induced by the 2 vaccines has been performed only up to 5 years. Among 3300 Finnish females aged 16-17 years who got 1 of the 2 HPV vaccines in phase 3 licensure trials, virtually all consented to registry-based long-term follow-up. Linkage with the Finnish Maternity Cohort found that they donated >2500 serum samples up to 12 years later. Sera of 337 (38.6%) Gardasil and 730 (30.3%) Cervarix vaccine recipients were retrieved from the Finnish Maternity Cohort biobank and type-specific anti-HPV antibody levels were determined using in-house multiplexed heparin-HPV pseudovirion Luminex assay. Anti-HPV-16 and anti-HPV-18 antibody levels remained stable and above natural infection-related antibody levels for up to 12 years for most vaccine recipients. The median antibody levels were higher among Cervarix recipients 7-12 years post vaccination (P < .0001). The stability of vaccine-induced antibody levels is in accordance with the high long-term protection reported previously. The differences in antibody levels induced by the 2 vaccines imply that continued follow-up to identify possible breakthrough cases and estimation of the minimal protective levels of serum antibodies is a research priority.

HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy

Genome-wide associations and HLA genotyping have revealed associations between HLA alleles and susceptibility to primary membranous nephropathy. However, associations with clinical phenotypes and kidney outcome are poorly defined. We previously identified DRB1*1501 and DRB1*0301 as independent risk alleles for primary membranous nephropathy. Here, we investigated HLA associations with demographic characteristics, anti-phospholipase A2 receptor (PLA2R) antibody, treatment response and kidney outcome after a median follow-up of 52 months in 258 patients. DRB1*0301, but not DRB1*1501, was associated with a significantly higher level of PLA2R antibody (odds ratio 1.58, 95% confidence interval 1.13-2.22). Although DRB1*1502, which differs from DRB1*1501 by a single amino acid, was not a risk allele for primary membranous nephropathy (odds ratio 1.01), it was associated with significantly lower estimated glomerular filtration rates both at baseline (1.79, 1.18-2.72) and at last follow-up (1.72, 1.17-2.53), a significantly worse renal outcome by Kaplan-Meier analysis and a significantly higher risk of end-stage renal disease by Cox regression analysis (hazard ratio 4.52, 1.22-16.74). Nevertheless, the absence of remission remained the only independent risk factor for end-stage renal disease by multivariate analysis. DRB1*1502 was also associated with a significantly higher median PLA2R antibody level [161.4 vs. 36.3 U/mL] and showed interaction with DRB1*0301 for this variable. Thus, HLA genes control PLA2R antibody production and primary membranous nephropathy severity and outcome. Additionally, DRB1*1502 behaves like a modifier gene with a strong predictor value when associated with HLA risk alleles. Other modifier genes need further investigations in larger cohorts.

Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure

ObjectiveTo assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity. Patients and MethodsWe searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab–seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated. ResultsOf 289 patients who met inclusion criteria, 163 (56.4%) were women, median age was 54 years (range, 10-87 years), median antibody level was 0.11 nmol/L (range, 0.05-22.10 nmol/L), and median CASS total score was 2.0 (range, 0-10). Using receiver operating characteristic curve analysis, a level above 0.40 nmol/L predicted severe AF (CASS score, ≥7) with 92% specificity and 56% sensitivity. For at least moderate AF (CASS score ≥4 and anhidrosis ≥25%), a level of at least 0.20 nmol/L had 80% specificity and 59% sensitivity. Levels below 0.20 nmol/L were not predictive of the presence or absence of AF. For predicting orthostatic hypotension, ganglionic AChR-Ab level had excellent specificity above 0.4 nmol/L but lacked sensitivity. Autoantibodies to additional targets were present in 61 patients (21.1%). ConclusionGanglionic AChR-Ab level of at least 0.40 nmol/L is a moderately sensitive and highly specific marker for severe AF, as is a level of at least 0.20 nmol/L for moderate AF if CASS score is coupled with anhidrosis of 25% or more, among patients with suspected ganglionic AChR-Ab autoimmune autonomic ganglionopathy. Antibody levels of less than 0.20 nmol/L have little clinical importance in the absence of clinical AF.

Quantitation of HBV cccDNA in anti-HBc-positive liver donors by droplet digital PCR: A new tool to detect occult infection

The accurate diagnosis of occult hepatitis B virus (HBV) infection (OBI) requires the demonstration of HBV DNA in liver biopsies of hepatitis B surface antigen-negative individuals. However, in clinical practice a latent OBI is deduced by the finding of the antibody to the hepatitis B core antigen (anti-HBc). We investigated the true prevalence of OBI and the molecular features of intrahepatic HBV in anti-HBc-positive individuals. The livers of 100 transplant donors (median age 68.2 years; 64 males, 36 females) positive for anti-HBc at standard serologic testing, were examined for total HBV DNA by nested-PCR and for the HBV covalently closed circular DNA (HBV cccDNA) with an in-house droplet digital PCR assay (ddPCR) (Linearity: R2 = 0.9998; lower limit of quantitation and detection of 2.4 and 0.8 copies/105 cells, respectively). A total of 52% (52/100) of the individuals studied were found to have OBI. cccDNA was found in 52% (27/52) of the OBI-positive, with a median 13 copies/105 cells (95% CI 5-25). Using an assay specific for anti-HBc of IgG class, the median antibody level was significantly higher in HBV cccDNA-positive than negative donors (17.0 [7.0-39.2] vs. 5.7 [3.6-9.7] cut-off index [COI], respectively, p = 0.007). By multivariate analysis, an anti-HBc IgG value above 4.4 COI was associated with the finding of intrahepatic HBV cccDNA (odds ratio 8.516, p = 0.009); a lower value ruled out its presence with a negative predictive value of 94.6%. With a new in-house ddPCR-based method, intrahepatic HBV cccDNA was detectable in quantifiable levels in about half of the OBI cases examined. The titer of anti-HBc IgG may be a useful surrogate to predict the risk of OBI reactivation in immunosuppressed patients. The covalently closed circular DNA (cccDNA) form of the hepatitis B virus (HBV) sustains the persistence of the virus even decades after resolution of the symptomatic infection (occult HBV infection). In the present study we developed a highly sensitive method based on droplet digital PCR technology for the detection and quantitation of HBV cccDNA in the liver of individuals with occult HBV infection. We observed that the amount of HBV cccDNA may be inferred from the titer in serum of the IgG class antibody to the hepatitis B core antigen. The quantitation of this antibody may represent a surrogate to determine which patients are at the highest risk of HBV reactivation following immunosuppressive therapies.

Rapid decline of anti-hepatitis C virus (HCV) antibodies following early treatment of incident HCV infections in HIV-infected men who have sex with men.

Following clearance of incident hepatitis C virus (HCV) infections, HCV antibody levels may decline, resulting in seroreversion. It is unclear to what extent HCV antibody level trajectories differ between patients with treatment-induced sustained virological response (SVR), those with spontaneous clearance and those with untreated replicating HCV infection. We investigated HCV antibody level dynamics in HIV-infected MSM with different clinical outcomes. We investigated anti-HCV antibody level dynamics following an incident HCV infection in 67 HIV-infected men who have sex with men (MSM) with different clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated replicating infection (n = 22). Antibody levels were measured at the time of HCV diagnosis, and at yearly intervals for 3 years thereafter. At baseline, median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5 sample to cut-off (S/CO) for SVR, spontaneous clearance and untreated infection, respectively. Over 3 years of follow-up, SVR was associated with a more pronounced decrease in anti-HCV levels compared with spontaneous clearance and untreated infection [median decline 71% [interquartile range (IQR: 43-87%), 38% (IQR: 29-60%) and 12% (IQR: 9-22%), respectively; P < 0.001]. Seroreversions occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with spontaneous clearance. A shorter delay between time of infection and treatment start correlated with higher rates of decline in antibody levels. Seven patients experienced a reinfection. Treatment-induced HCV clearance was associated with a more pronounced decline in anti-HCV antibody levels and with higher rates of seroreversion compared with spontaneous clearance or untreated replicating HCV infection among HIV-infected MSM with incident HCV infections. Rapid clearance of HCV RNA following early HCV treatment might impair the development of persistent antibody titres.

Transcriptome of Porcine PBMCs over Two Generations Reveals Key Genes and Pathways Associated with Variable Antibody Responses post PRRSV Vaccination

Porcine reproductive and respiratory syndrome virus (PRRSV) is a virus susceptible to antibody dependent enhancement, causing reproductive failures in sows and preweaning mortality of piglets. Modified-live virus (MLV) vaccines are used to control PRRS in swine herds. However, immunized sows and piglets often generate variable antibody levels. This study aimed to detect significant genes and pathways involved in antibody responsiveness of pregnant sows and their offspring post-PRRSV vaccination. RNA sequencing was conducted on peripheral blood-mononuclear cells (PBMCs), which were isolated from pregnant sows and their piglets with high (HA), median (MA), and low (LA) PRRS antibody levels following vaccination. 401 differentially expressed genes (DEGs) were identified in three comparisons (HA versus MA, HA versus LA, and MA versus LA) of sow PBMCs. Two novel pathways (complement and coagulation cascade pathway; and epithelial cell signaling in H. pylori infection pathway) revealed by DEGs in HA versus LA and MA versus LA were involved in chemotactic and proinflammatory responses. TNF-α, CCL4, and NFKBIA genes displayed the same expression trends in subsequent generation post-PRRS-MLV vaccination. Findings of the study suggest that two pathways and TNF-α, CCL4, and NFKBIA could be considered as key pathways and potential candidate genes for PRRSV vaccine responsiveness, respectively.

Comparative tetanus antibody response of Nigerian children to diphtheria-pertussis-tetanus and pentavalent vaccines.

In Nigeria and many parts of the world, the pentavalent vaccine is replacing the diphtheria-pertussis-tetanus (DPT) vaccine in tetanus prevention. The aim of this study was to compare the anti-tetanus immunoglobulin G (IgG) response of children who received DPT with those who received the pentavalent vaccine. A cross-sectional survey of anti-tetanus IgG levels in children aged 6 months to 5 years who received DPT and in children who received the pentavalent vaccine. IgG antibody levels were determined using enzyme-linked immunosorbent assay. The protective level was set at ≥0.1 IU/ml. One hundred and twenty-two out of 130 children (93.9%) who had received DPT had protective levels of anti-tetanus IgG compared to 278 out of 288 children (96.5%) who had received the pentavalent vaccine. The difference was not statistically significant (P = 0.21). The median IgG antibody level in those who received DPT was 1.1 IU/ml (interquartile range (IQR) 0.4-1.8) compared with 0.6 IU/ml (IQR 0.4-1.4) in those who received pentavalent vaccine (P = 0.006), with age being the only predictor of variability in the multivariate analysis. DPT and pentavalent vaccines are equally effective in inducing protective levels of anti-tetanus IgG in children. Vaccination with the pentavalent vaccine, which is the current policy in Nigeria and many other parts of the world, should continue.

The Effect of Concurrent Tetanus-diphtheria Vaccination on the Antibody Response to Rabies Vaccine: A Preliminary Study.

The number of studies in the literature investigating the effect of tetanus vaccination on rabies prophylaxis is rather limited. In this study, we aimed to investigate the effect of concurrent tetanus-diphtheria (Td) vaccination on the antibody response to rabies vaccine. The data of consecutive 80 patients who presented to Sakarya University Training and Research Hospital, Department of Emergency due to rabies suspected exposure between 15 October 2012 and 12 June 2013 were enrolled to this study. Postexposure rabies prophylaxis had been given to all cases, however concurrent tetanus vaccination had been administered to some of them according to their need. Cases were divided into two parts according to their receipt of tetanus prophylaxis as rabies only group (group R, n=37), and rabies and tetanus-diphtheria group (group R+Td, n=43). Rabies antibody levels were tested in sera of the cases at first and postvaccination 21st day. The median antibody levels of each group were measured and compared with each other statistically. In our study, postvaccination 21st day antibody level of group R was 0.68 IU/ml (IQR: 0.79), while the same for group R+Td was 0.52 IU/ml (IQR: 0.48) (p=0.022). Concurrent administration of Td vaccine was found to have a significant negative effect on the antibody response to rabies vaccine. Our results should be confirmed with further studies including more cases.

Epidemiological study of antibody to pertussis toxin IgG in newborns in Shunyi District of Beijing in 2016

Objective To investigate the levels of antibody to pertussis toxin (PT) IgG in newborns in Shunyi Women and Children's Hospital of Beijing Children's Hospital in 2016. Methods A total of 419 newborns were enrolled in this study. Umbilical cord blood sample was collected from each subject and detected by enzyme-linked immunosorbent assay to measure the concentration of PT-IgG. Besides, all newborns were followed up to January 31, 2017. Chi-square test was used for statistical analysis. Results The detectable rate of umbilical cord blood samples for PT-IgG accounted for 30.1% (126/419). The median antibody level was <5 U/ml, and the 90th and the 95th percentile were 14.3 and 24.0 U/ml, respectively. No cases of pertussis occurred at the end of follow-up. Conclusions The newborns born in Shunyi Women and Children's Hospital of Beijing Children's Hospital are generally lack of protective PT antibody. Key words: Pertussis toxin; Immunoglobulin G; Whooping cough; Fetal blood; Epidemiologic studies; Infant, newborn