Serum Titers Research Articles

Comparison of antibody responses of heterologous and homologous Covid-19 booster vaccination: an observational study

ObjectivePakistan has been seriously affected by the COVID-19 pandemic, with numerous waves of infection. Using different vaccine and booster doses was a key component to control and combat this pandemic. This study aims to monitor the heterologous and homologous booster vaccination doses that generate immune responses in healthy adults after 9 months of vaccination.MethodsIn this cross-sectional, observational study a total of 173 samples were collected. Participants from both genders (Male and Female) between the ages of 18 to 25 years were enrolled for the study. Participants who had booster shots of homologous Sinopharm BBIBP CorV and heterologous Pfizer-BioNTech vaccines were included only, with the use of a Roche Cobas-e601 analyzer, the antibody titers in the blood serum were quantified by the ECLIA method. IBM SPSS 22 was utilized for descriptive statistical analysis and P< 0.05 was considered significant.ResultsIn this study the IgG antibody levels were measured against the full length of receptor binding domain (RBD) of the spike (S) protein. The mean antibody titer in the Pfizer group was 9764 ± 10976 U/mL and 5762 ± 4302 U/mL in the Sinopharm group. The Mean IgG antibody levels of the Pfizer-vaccinated group were significantly higher than the Sinopharm-vaccinated group (P=0.000, each). Comparing the Sinopharm BBIBP CorV booster dosage to the Pfizer booster, Pfizer BNT162b2demonstrated a stronger immune response. However, there were no immunological gender-specific significant differences. The administration of a third dosage of Pfizer BNT162b2 after two doses of BBIBP CorVConclusionThe administration of a third dosage of Pfizer BNT162b2 after two doses of BBIBP-CorV is recommended to boost the humoral immune response in the general population while there was no gender-specific difference observed. More effectiveness can be attained by administering additional doses due to the antibody decay.

Evaluation of Infectivity, Length of Infection, and Immune Response of Avian Reovirus Variants in Egg-laying Hens.

ABSTRACTWe conducted research studies on avian reovirus (ARV) infectivity in egg-laying hens, focusing on three variants (δC genotypes 2, 3, and 5) detected in layer chickens in Pennsylvania to date. Day-old chicks (Hy-Line North America, LLC, PA), raised at the Poultry Education and Research Center of Penn State University Park campus, showed healthy growth and normal egg production after 20 weeks of age. ARV variants were propagated in LMH cell cultures, with concentrations measured at TCID50/mL. Each group of 10 hens received a 1.0 mL dose containing 103 to 104 TCID50/mL of one ARV variant through oral, nasal, and ocular routes. Infected hens showed normal egg production, with minimal symptoms of watery droppings in the first-week post-inoculation (pi). Cloacal and oral pharyngeal swabs were collected daily in the first week pi and every other day in the second-week pi to monitor virus shedding. Virus shedding began 24 hours pi through feces, peaked at 2 to 4 days pi, decreased by 5 to 7 days pi, and ceased after 12 to 14 days pi. A few birds' oral pharyngeal swabs were weakly positive for 1 to 3 days pi, then all turned negative. Infected hens developed high serum and egg yolk antibody titers at 2 to 3 weeks pi, showing 100% protection against subsequent infections with the same variant strain, demonstrating a 100% protection rate.

Significance of HBsAg Expression in Placental Tissue with Serum Positivity in Hepatitis B Virus-infected Mother

Introduction: Hepatitis B virus infection in fetal and newborn may result from the intrauterine vertical transmission. The purpose of our study is to determine the association between HBsAg expression in the placental and HBsAg serum in pregnant women. Methods: Total 67 placental tissues and serum were obtained from HBV-infected mothers. This study was conducted in various hospitals in Makassar, Indonesia from December 2017 until August 2018. Maternal serum and placental tissues were tested by ELISA and Immunohistochemistry staining. Results: 67 samples from placental tissues and serum were categorized into two different levels of serum titer and staining positivity. Twenty nine samples (43.3%) were categorized in low titer of HBsAg positive serum and 38 samples (56.7%) in high titer of HBsAg positive serum. From the total of 67 placental samples, 43 (64.2%) samples had positive expression of HBsAg immunohistochemistry staining and 24 (34.8%) samples had negative expressions. Conclusions: There was a significant correlation between the expressions of HBsAg in the placental tissues and serum titers of HBV-infected mothers that is important in predicting the risk of transplacental transmission. The results of this study can be used as guidelines for the prevention and therapeutic approach of mother-to-child HBV infection.

The Proportion of Ocular Involvement and Characteristics of Dry Eye Parameters in Primary Sjögren's Syndrome Referred from the Rheumatology Department.

To report the proportion of ocular involvement in primary Sjögren's syndrome (pSS) and to analyze various dry eye indexes and serum titers of markers depending on whether ocular involvement has occurred or not. This retrospective study considered 214 patients referred from the rheumatology department for pSS workup. Symptom questionnaires, ocular surface stain score (OSS), Schirmer test, tear break-up time (TBUT), meibomian gland (MG) dropout, meibum quality, meibum expressibility, lid margin abnormalities, and lipid layer thickness were evaluated. Anti-Ro Ab, anti-La Ab, ANA, RF, ESR, and CRP were included as systemic serum titers of markers. Patients with (Group 1) and without (Group 2) ocular involvement were compared. We conducted a further subgroup analysis of group 1 by dividing it into two groups based on whether or not the cases met all the ocular criteria for pSS diagnosis. Among the 214 referred patients, 118 were diagnosed as pSS: 87 out of 118 (74%) in group 1 and 31 (25%) in group 2. Group 1 showed higher meibum quality scores (p=0.016), meibum expressibility (p=0.01), and lid margin abnormalities on the lower lid (p=0.029) and lower TBUT (p=0.016) than group 2. Among the serum titers of markers, anti-Ro Ab negatively correlated with TBUT (r=-0.211, p=0.028). OSS, TBUT, and the schirmer test statistically differed between the patients who satisfied both ocular criteria (N=46) and those who satisfied only one criterion (N=41) (p=<0.001, 0.041, 0043, respectively). There were no statistical differences in serum titers of markers between the two groups. About half of patients referred from the rheumatology department for diagnosis of pSS were diagnosed with pSS. The proportion of ocular involvement in the pSS patients was 74%, and half of these patients met both ocular criteria. Only anti-Ro Ab negatively correlated with TBUT. Also, OSS, TBUT, and schirmer test were statistically different between the two subgroups.

Comparative Analysis of Newcastle Disease Seroprevalence in Different Breeds of Pigeon Populations in Chattogram Bangladesh

This study was performed to determine the antibody against Newcastle disease and serum protein level in pigeons of Chattogram, Bangladesh. The results were evaluated in pigeons of different groups of age, sex, and breed by applying the hemagglutination inhibition (HI) test. A total of 90 pigeons were selected for this research. Antibody titer against Newcastle Disease virus was analyzed according to the different age groups, sex, breeds and clinical signs of ND infection of pigeons by X2 test. Incase of less than 6 month age pigeons 73% (n=22) were HI titer positive whereas more than 6 months but less than 1 year 56% (n=32) were HI negative. There was no significant variation among different sex. In both male and female pigeon groups, the percentage of HI titer-positive pigeons in females and males was 51.7% and 57.4% respectively. There was significant variation among the different breeds and equal percentages of HI titer positive and negative pigeons were found in Giribaj and local breeds whereas 100% were found in King and Owl breeds and 80% were found in the Siraji breed. There was significant variation among NDV-infected and non-infected pigeons and equal percentage of HI titer negative and positive pigeons were found in ND non- infected, whereas (80.8%) were found in ND infected pigeons. A paired test was done between HI titer and total serum protein. There was a significant (t&lt;0.0) difference among the group. In the case of HI titer mean was about 23 titer and the standard error was 0.28. In the case of total serum protein mean was 4.45 and the standard error was 0.19.

Comparative Analysis of Newcastle Disease Seroprevalence in Different Breeds of Pigeon Populations in Chattogram, Bangladesh

This study was performed to determine the antibody against Newcastle disease and serum protein level in pigeons of Chattogram, Bangladesh. The results were evaluated in pigeons of different groups of age, sex, and breed by applying the hemagglutination inhibition (HI) test. A total of 90 pigeons were selected for this research. Antibody titer against Newcastle Disease virus was analyzed according to the different age groups, sex, breeds, and clinical signs of ND infection of pigeons by X2 test. In the case of fewer than 6 months of age pigeons, 73% (n=22) were HI titer positive whereas more than 6 months but less than 1 year 56% (n=32) were HI negative. There was no significant variation among the different sexes. In both male and female pigeon groups, the percentage of HI titer-positive pigeons in females and males was 51.7% and 57.4% respectively. There was significant variation among the different breeds and equal percentages of HI titer positive and negative pigeons were found in Giribaj and local breeds whereas 100% were found in King and Owl breeds and 80% were found in the Siraji breeds. There was significant variation among NDV-infected and non-infected pigeons and an equal percentage of HI titer negative and positive pigeons were found in ND non-infected, whereas (80.8%) were found in ND-infected pigeons. A paired test was done between HI titer and total serum protein. There was a significant (t&lt;0.0) difference among the groups. In the case of HI titer mean was about 23 titer and the standard error was 0.28. In the case of total serum protein mean was 4.45 and the standard error was 0.19.

Human and hamster sera correlate well in identifying antigenic drift among SARS-CoV-2 variants, including JN.1.

Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with fivefold to sixfold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a fivefold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.IMPORTANCEUpdates to COVID-19 vaccine antigens depend on assessing how much vaccine antigens differ antigenically from newer SARS-CoV-2 variants. Human sera from single variant infections are ideal for discriminating antigenic differences among variants, but such primary infection sera are now rare due to high population immunity. It remains unclear whether sera from experimentally infected animals could substitute for human sera for antigenic assessments. This report shows that neutralization titers of variant-matched human and hamster primary infection sera correlate well and recognize variants similarly, indicating that hamster sera can be a proxy for human sera for antigenic assessments. We further show that human sera following an XBB.1.5 booster vaccine broadly neutralized XBB sub-lineage variants but titers were fivefold lower against the more recent JN.1 variant. These findings support updating the current COVID-19 vaccine variant composition and developing a framework for assessing antigenic differences in future variants using hamster primary infection sera.

Hepatitis B and/or C virus reactivation in patients receiving chemotherapy: An observational study

Background: Viral hepatitis reactivation occurs during various chemotherapy treatments. Patients with high serum titer levels of Hepatitis B virus (HBV) DNA before chemotherapy and those receiving intensive chemotherapy for hematological malignancies are particularly at risk. Aims and Objectives: This study aimed to determine the incidence, predictors, and clinical significance of HBV and hepatitis C virus reactivations during chemotherapy. Materials and Methods: This prospective observational study was conducted at a tertiary care center. Hepatitis B and C virus status was identified before the initiation of cancer treatment. Liver function was monitored in all patients before each cycle of chemotherapy. Patients with deranged liver function were subjected to repeated viral antigen tests and DNA/RNA titer levels. Results: A total of 110 patients were identified as having hepatitis virus reactivation out of 1190 patients. The sites of malignancy were breast, 39.1% (43 patients); colorectal, 11.8% (13 patients); upper gastrointestinal, 10% (11 patients); ovary, 9.1% (10 patients); hematological malignancies, 8.2% (9 patients); lung, 5.6% (6 patients); genitourinary, 4.5% (5 patients); head-and-neck, 4.5% (5 patients); biliary tract, 3.6% (4 patients); brain tumor, 1.8% (2 patients); and others, 1.8% (2 patients). Most of the patients with reactivation received 5-FU/Capecitabine-based chemotherapy 37.3%, (41 patients), taxane plus platinum (10.9%, 12 patients), taxane only (10%, 11 patients), trastuzumab (8.2%, 9 patients), platinum-based (6.4%, 7 patients), tyrosine kinase inhibitors (6.4%, 7 patients), monoclonal antibodies (MABs) (3.6%, 4 patients), anthracyclines (2.7%, 3 patients), immunomodulators (2.7%, 3 patients), and other agents (11.8%, 13 patients). Conclusion: We recommend that Hepatitis B and C virus Screening must me performed before chemotherapy and that non-reactive patients should be vaccinated.

Seropositivity to louping ill virus in dogs in the UK.

Louping ill virus (LIV) is a tick-borne flavivirus that can cause fatal meningoencephalomyelitis in dogs. Four dogs with confirmed LIV infection and a case series of dogs with suspected flavivirus infection have been reported in the UK. However, underreporting of LIV infection due to lack of testing is suspected. Surplus serum/plasma from 220 dogs was used to determine the seroprevalence of LIV by haemagglutination inhibition (HAI) test. Signalment and environmental factors were investigated for potential correlations with a positive titre (serum dilution of 1:20 or more). Two hundred and two dogs were suitable for inclusion in the study, nine of which (4.5%) were seropositive. Among the dogs investigated for neurological disease (40/202; 19.8%), six (15%) were seropositive. Ectoparasiticide use approached significance (p = 0.055) for being protective against LIV seropositivity. The main limitations were the specificity of the HAI test, the relatively small number of samples, the low number of seropositive dogs, the poor geographical distribution of the samples and the inherent limitations of questionnaire-based research. The seroprevalence of LIV in the UK dog population appears to be low. However, LIV should be considered in dogs presenting with unexplained acute or subacute progressive neurological clinical signs, especially because of the recent reports of several dogs with clinical flavivirus infections.

Variant-specific neutralising antibodies levels induced by the PHH-1 V SARS-CoV-2 vaccine (Bimervax®) by HIPRA

SARS-CoV-2 virus variants continue to emerge at an alarming rate due to spontaneous genetic mutations, particularly in the spike protein receptor-binding domain (RBD) portion, which render the virus more likely to escape immunity. So far, the immunity obtained through global primary and/or booster immunisation campaigns has been sufficient to protect the population from new emerging variants of the Omicron lineage. The current approach to update vaccines' antigen composition to new variants to boost immunity may not be sustainable in the long term. It might also be potentially redundant if the mutations are giving rise to variants which induce milder infections and existing vaccines, such as Bimervax®, are still sufficiently protective, as Covid is slowly becoming a seasonal illness. Through measuring neutralising antibody titres in sera from subjects boosted with Bimervax®, we have demonstrated the ability of Bimervax® to induce immune responses against a variety of SARS-CoV-2 variants, ranging from earlier variants inducing more serious infections to more recent variants which have been found to produce milder infections.

Association of Encephalitozoon cuniculi with Clinical Signs and Abnormal Hematologic/Biochemical Changes in Pet Rabbits in Thailand.

Encephalitozoon cuniculi can cause serious disease and subclinical infection in rabbits and requires active surveillance to control the infection. This study investigated the association between anti-Encephalitozoon cuniculi antibody status and various health parameters in pet rabbits. A total of 90 rabbits were divided into healthy (N = 30), subclinical (N = 30), and clinical (N = 30) groups based on their anti-Encephalitozoon cuniculi antibody status and clinical presentations. The mean ages of the control (37 ± 40 months) and subclinical groups (38 ± 34 months) were notably lower compared to that of the clinical group (63 ± 38 months, p < 0.01). Serum titers for anti-Encephalitozoon cuniculi antibodies were significantly elevated in rabbits with subclinical and clinical infections compared to those of healthy rabbits (p < 0.05). Neurological signs were predominant in rabbits with active E. cuniculi infection (80.0%), with additional pathological features including urinary dysfunction (10.0%) and cataracts (10.0%). The source of rabbits was not associated with E. cuniculi infection (p = 0.159). Anemia was significantly linked to E. cuniculi infection (p = 0.026); however, no significant associations were found with leukocytosis, thrombocytopenia, or serum biochemistry parameters. Mature adult rabbits were more likely to be infected with E. cuniculi. Recognizing anemia and neurological signs facilitates in early diagnosis of E. cuniculi infection.

Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks.

The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.

Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF. Urinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies. PwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified different associations of urinary injury markers with aminoglycoside exposure, lung function, and neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and decreased lung function was most prominent in patients harboring chronic Pseudomonas aeruginosa infection. Increased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and high Pseudomonas aeruginosa burden suggests that pulmonary disease may contribute to renal injury in CF.

Safety and Immunogenicity of a Carbohydrate Fatty Acid Monosulphate Ester Adjuvant Combined with a Low-Dose Quadrivalent Split-Virion Inactivated Influenza Vaccine: A Randomised, Observer-Blind, Active-Controlled, First-in-Human, Phase 1 Study.

Seasonal influenza vaccine effectiveness is low. Carbohydrate fatty acid monosulphate ester (CMS), a new oil-in-water adjuvant, has proven potency in animal models with suggested capacity for dose-sparing. The objective was to evaluate safety and immunogenicity of CMS when added to a low-dose influenza vaccine (QIV) in humans. In a randomised, double-blind, active-controlled, first-in-human study, sixty participants (18-50 years) received either 0.5 mg CMS or 2 mg CMS with 1/5th dose QIV, or a full dose QIV without CMS. Adverse events (AE) were monitored until 7 days post-vaccination. Haemagglutinin inhibition (HI) titres in serum and CD4+ T cells in PBMCs were determined at day 0, 7, 28, and 180. Mean age was 37.6 (±10.1) years and 42/60 (70.0%) were female. Pain at injection site (42/60, 86.7%) and headache (34/60, 56.7%) were reported most and more frequently in the 2 mg CMS group. HI titres and the frequency of influenza specific CD4+ T cells were equal across strains for the three cohorts on all visits, increased until day 28 and decreased at day 180 to values higher than baseline. CMS was safe in humans. Humoral and cell-mediated immunogenicity was similar across vaccines, even with 1/5th antigen dose. CMS can have beneficial implications in low-resource settings or in a pandemic context.

Evaluation of the Relationship of HBsAg Serum Plasma Values with HBV DNA and Other Serologic Markers in the Diagnosis of Hepatitis B

Objective: Hepatitis B virus (HBV) infections cause a major public health problem worldwide diagnosis and treatment of HBV infection is an important issue. Detection of HBV DNA by polymerase chain reaction (PCR) and demonstration of viral replication together with serologic and biochemical indicators are very useful in diagnosis and treatment. In this study, we aimed to evaluate the relationship between HBsAg serum concentration values and other serologic parameters related to HBV in the diagnosis of hepatitis B. Methods: HBsAg, HBV DNA, Anti HBc IgG, Anti HBc IgM, HBeAg, and Anti HBe values obtained from blood sera taken from patients in Sivas Cumhuriyet University Application and Research Hospital Microbiology Laboratory between 2012-2020 were retrospectively analyzed from laboratory records. Results: A positive correlation was found between HBsAg serum titers and HBV DNA and between HBeAg and HBV DNA. It was found that HBV DNA positivity rates increased as HBsAg titers increased. Similarly, it was found that HBc IgG positivity increased as HBsAg titers increased. HBeAg positivity increased with increasing HBsAg titers up to a certain point, while HBeAg positivity decreased after a certain titer. When HBV DNA results were compared with HBeAg results, the relationship between the two values was found to be significant. Conclusion: We think that it is useful to investigate the relationship between serum concentrations of HBsAg and HBV DNA and other serologic parameters in the accurate identification of HBV infection and monitoring of treatment.

The significance of low titer serum cryptococcal antigen testing from 2017 to 2023 performed in a tertiary care center.

Several false positive low serum cryptococcal antigen (SCrAg) reports by lateral flow assay (LFA) were identified in late 2016 at our tertiary care hospital. After the recall and correction of the problem in the reagent, we studied the significance of SCrAg LFA≤1:10 from January 2017 to October 2023. Of 20 patients with 31 samples of SCrAg LFA≤1:10, 14 patients (70%) were classified as true positives, four (20%) were indeterminate, and only two (10%) patients were false positives. If a new SCrAg LFA≤1:10 is detected, it should be repeated, and additional workup should be pursued.

The genetic resistance of sows to Escherichia coli F4 adhesion reduces their response to a vaccine containing F4 fimbriae but does not affect the preweaning performance of their susceptible piglets.

Pigs without intestinal receptors for F4 fimbriae are congenitally resistant to F4 fimbriae-bearing enterotoxigenic Escherichia coli (ETEC F4). In general, 50 % and 100 % of piglets born to resistant (RR) sows crossed with hetero- or homozygous susceptible (SR, SS) boars, respectively, are susceptible but do not receive colostral antibodies against F4 fimbriae unless the sows have been vaccinated. The question arises as to whether resistant sows produce protective amounts of F4 antifimbrial antibodies after vaccination. The serum and colostrum antibody titres of 12 resistant and 12 susceptible vaccinated gilts were compared. The effect of the receptor status of the dam and sire on the preweaning performance of 5027 piglets was evaluated using Agroscope's recordings. The sows of the experimental herd, where ETEC F4 was circulating, were vaccinated against ETEC twice during the first pregnancy and once during each following pregnancy. The log2 transformed F4 antibody titres in the serum obtained after the second vaccine injection as well as in the colostrum of the 12 resistant animals were lower than the titres of the susceptible animals (serum: F4ab 11,19 ± 1,44 vs. 12,18 ± 1,33, P = 0,096; F4ac 10,03 ± 1,58 vs. 11,59 ± 1,43, P = 0,019; colostrum: F4ab 12,20 ± 2,41 vs. 14,02 ± 1,31, P = 0,033; F4ac 10,93 ± 2,46 vs. 13,03 ± 5,21, P = 0,006). The heat labile enterotoxin (LT) antibody titres after vaccination did not differ between susceptible and resistant animals (p > 0,10). Preweaning mortality in the offspring of RR sows × SS boars was slightly lower than in the offspring of SS sows × RR boars (P = 0,04), suggesting that the disease risk of susceptible piglets born to vaccinated resistant sows was not increased, even though they received colostrum with a slightly reduced content of antibody against F4 fimbriae.

Different Patterns of Autoantibody Secretion by Peripheral Blood Mononuclear Cells in Autoimmune Nodopathies.

Autoimmune nodopathies with antibodies against the paranodal proteins show a distinct phenotype of a severe sensorimotor neuropathy. In some patients, complete remission can be achieved after treatment with rituximab whereas others show a chronic course. For optimal planning of treatment, predicting the course of disease and therapeutic response is crucial. We stimulated peripheral blood mononuclear cells in vitro to find out whether secretion of specific autoantibodies may be a predictor of the course of disease and response to rituximab. Three patterns could be identified: In most patients with anti-Neurofascin-155-, anti-Contactin-1-, and anti-Caspr1-IgG4 autoantibodies, in vitro production of autoantibodies was detected, indicating autoantigen-specific memory B cells and short-lived plasma cells/plasmablasts as the major source of autoantibodies. These patients generally showed a good response to rituximab. In a subgroup of patients with anti-Neurofascin-155-IgG4 autoantibodies and insufficient response to rituximab, no in vitro autoantibody production was found despite high serum titers, indicating autoantibody secretion by long-lived plasma cells outside the peripheral blood. In the patients with anti-pan-Neurofascin autoantibodies-all with a monophasic course of disease-no in vitro autoantibody production could be measured, suggesting a lack of autoantigen-specific memory B cells. In some of them, autoantibody production by unstimulated cells was detectable, presumably corresponding to high amounts of autoantigen-specific plasmablasts-well in line with a severe but monophasic course of disease. Our data suggest that different B-cell responses may occur in autoimmune nodopathies and may serve as markers of courses of disease and response to rituximab.

Indocyanine green angiography reveals choroidal hypoperfusion in subacute sclerosing panencephalitis (SSPE).

We report the choroidal findings on indocyanine green angiography (ICGA) in two cases of subacute sclerosing panencephalitis (SSPE). The two immunocompetent patients (31-year-old and 30-year-old Asian Indian males) presented with acute-onset rapidly progressing vision loss with findings of necrotizing retinitis involving the central macula. Both patients tested negative for serological evidence of herpes or varicella, and toxoplasma antibodies. The patients demonstrated high serum and cerebrospinal fluid titers of anti-measles antibody (and abnormal electroencephalogram in one patient) leading to the diagnosis of SSPE. ICGA of both patients revealed distinct "dark dots" which showed hypofluorescence in the early and late phases suggestive of choroidal involvement/hypoperfusion. Choroidal involvement in SSPE has not been evaluated before and must be considered in the pathological manifestations of the disease.

Management of Red Cell Alloimmunization in Pregnancy.

Rhesus immune globulin has resulted in a marked decrease in the prevalence of RhD alloimmunization in pregnancy; however, antibody formation to other red cell antigens continues to occur. Evaluation for the presence of anti-red cell antibodies should be routinely undertaken at the first prenatal visit. If anti-red cell antibodies are detected, consideration of a consultation or referral to a maternal-fetal medicine specialist with experience in the monitoring and treatment of these patients is warranted. Cell-free DNA can be used to determine fetal red cell antigen status to determine whether the pregnancy is at risk of complications from the red cell antibodies. First-time sensitized pregnancies are followed up with serial maternal titers, and, when indicated, serial Doppler assessment of the peak systolic velocity in the middle cerebral artery should be initiated by 16 weeks of gestation. When there is a history of an affected fetus or neonate, maternal titers are less predictive of fetal risk; if the fetus is antigen positive, serial peak systolic velocity in the middle cerebral artery measurements should be initiated by 15 weeks of gestation because intraperitoneal intrauterine blood transfusions can be used at this gestation if needed. The mainstay of fetal therapy involves intrauterine transfusion through ultrasound-directed puncture of the umbilical cord with the direct intravascular injection of red cells. A perinatal survival rate exceeding 95% can be expected at experienced centers. Neonatal phototherapy and "top-up" transfusions attributable to suppressed reticulocytosis often are still required for therapy after delivery.