Mean Antibody Levels Research Articles

The Underlying Pathology of Autoimmune Thyroid Disease is Il-22 Independent

The thyroid gland is frequently associated with autoimmune disease. It produces thyroid hormones responsible for controlling cellular metabolism. The current case control study involved ninety subjects which were assigned into two equal-numbered groups of patients and apparently healthy controls. For laboratory evaluation, five millilitres of venous blood were withdrawn from individual participants, serum were collected and stored at –20 oC to be analysed. Immunoassay technique was used to measure the serum level of thyroid stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3). While ELISA technique was used for measuring the serum levels of anti-thyroid peroxidase (anti-TPO) antibodies and IL-22. The results of the current study showed that, in the patient group, thirty eight (84.44 %) subjects were diagnosed with hypothyroidism, represented by thirty five female (77.77 %) and three male (6.67 %); furthermore, seven individuals (15.56 %) were grouped as hyperthyroid patients and represented by five females (11.11 %) and two males (4.45 %). The results also demonstrated that the serum TSH levels (12.04 ± 2.76) for the patients were significantly (p< 0.05) higher than that of the control group (1.87 ± 0.15). Whereas, T3 and T4 mean serum levels ± SE were 2.05 nmol/l ±0.14; 100.66 nmol/l ± 4.76 and 2.14 nmol/l ± 0.07; 105.37 nmol/l ± 2.92 for patient and control categories, respectively. The findings of this work showed that mean serum level (IU/ml) of anti-thyroidperoxidase antibody in patient group differed significantly (P <0.05) in comparison to control group (represented by 259.08±59.99 and 8.71 ±1.23, respectively). No statistical difference was non-significant when comparison involved mean serum concentration levels of IL-22 for patients (157.22 ng/ml ± 24.81) and controls (157.08 ng/ml ± 24.80). In conclusion: IL-22 cannot be proposed as an essential factor participating the development and/or the progression of autoimmune thyroid disease (AITD).

Immune Response Following Quadrivalent Human Papillomavirus Vaccination in Women After Hematopoietic Allogeneic Stem Cell Transplant

Human papillomavirus (HPV) infection is found in about 40% of women who survive allogeneic hematopoietic stem cell transplant and can induce subsequent neoplasms. To determine the safety and immunogenicity of the quadrivalent HPV vaccine (HPV-6, -11, -16, and -18) in clinically stable women post-allogeneic transplant compared with female healthy volunteers. Participants received the quadrivalent HPV vaccine in intramuscular injections on days 1 and 2 and then 6 months later. This prospective, open-label phase-1 study was conducted in a government clinical research hospital and included clinically stable women posttransplant who were or were not receiving immunosuppressive therapy compared with healthy female volunteers age 18 to 50 years who were followed up or a year after first receiving quadrivalent HPV vaccination. The study was conducted from June 2, 2010, until July 19, 2016. After all of the results of the study assays were completed and available in early 2018, the analysis took place from February 2018 to May 2019. Anti-HPV-6, -11, -16, and -18-specific antibody responses using L1 virus-like particle enzyme-linked immunosorbent assay were measured in serum before (day 1) and at months 7 and 12 postvaccination. Anti-HPV-16 and -18 neutralization titers were determined using a pseudovirion-based neutralization assay. Of 64 vaccinated women, 23 (35.9%) were receiving immunosuppressive therapy (median age, 34 years [range, 18-48 years]; median 1.2 years posttransplant), 21 (32.8%) were not receiving immunosuppression (median age, 32 years [range, 18-49 years]; median 2.5 years posttransplant), and 20 (31.3%) were healthy volunteers (median age, 32 years [range, 23-45 years]). After vaccine series completion, 18 of 23 patients receiving immunosuppression (78.3%), 20 of 21 not receiving immunosuppression (95.2%), and all 20 volunteers developed antibody responses to all quadrivalent HPV vaccine types (P = .04, comparing the 3 groups). Geometric mean antibody levels for each HPV type were higher at months 7 and 12 than at baseline in each group (all geometric mean ratios >1; P < .001) but not significantly different across groups. Antibody and neutralization titers for anti-HPV-16 and anti-HPV-18 correlated at month 7 (Spearman ρ = 0.92; P < .001 for both). Adverse events were mild and not different across groups. Treatment with the HPV vaccination was followed by strong, functionally active antibody responses against vaccine-related HPV types and no serious adverse events. These findings suggest that HPV vaccination may be safely administered to women posttransplant to potentially reduce HPV infection and related neoplasia. ClinicalTrials.gov Identifier: NCT01092195.

Safety and immunogenicity of a 30-valent M protein-based group a streptococcal vaccine in healthy adult volunteers: A randomized, controlled phase I study

BackgroundStreptococcus pyogenes (group A Streptococcus, Strep A) is a widespread pathogen that continues to pose a significant threat to human health. The development of a Strep A vaccine remains an unmet global health need. One of the major vaccine strategies is the use of M protein, which is a primary virulence determinant and protective antigen. Multivalent recombinant M protein vaccines are being developed with N-terminal M peptides that contain opsonic epitopes but do not contain human tissue cross-reactive epitopes. MethodsWe completed a Phase I trial of a recombinant 30-valent M protein-based Strep A vaccine (Strep A vaccine, StreptAnova™) comprised of four recombinant proteins containing N-terminal peptides from 30 M proteins of common pharyngitis and invasive and/or rheumatogenic serotypes, adjuvanted with aluminum hydroxide. The trial was observer-blinded and randomized in a 2:1 ratio for intramuscular administration of Strep A vaccine or an alum-based comparator in healthy adult volunteers, at 0, 30 and 180 days. Primary outcome measures were assessments of safety, including assays for antibodies that cross-reacted with host tissues, and immunogenicity assessed by ELISA with the individual vaccine peptides and by opsonophagocytic killing (OPK) assays in human blood. ResultsTwenty-three Strep A-vaccinated participants and 13 controls completed the study. The Strep A vaccine was well-tolerated and there was no clinical evidence of autoimmunity and no laboratory evidence of tissue cross-reactive antibodies. The vaccine was immunogenic and elicited significant increases in geometric mean antibody levels to 24 of the 30 component M antigens by ELISA. Vaccine-induced OPK activity was observed against selected M types of Strep A in vaccinated participants that seroconverted to specific M peptides. ConclusionThe Strep A vaccine was well tolerated and immunogenic in healthy adults, providing strong support for further clinical development. [ClinicalTrials.gov NCT02564237].

Fasciola hepatica in a country of low incidence: a tricky diagnosis.

Fasciola hepatica is a foodborne trematode present worldwide. Definitive hosts are mostly ruminants such as cattle and sheep, as well as humans. In Switzerland, Fasciola infection in humans is rare. Unfortunately, many patients are likely to undergo multiple unnecessary investigations before the parasite is suspected and fascioliasis diagnosed, especially if symptoms are unspecific. Retrospective analysis of all patients diagnosed with Fasciola hepatica at the University Hospital of Bern between 2005 and 2018. Diagnosis was positive if a positive serology and/or eggs in stool samples correlated with clinical presentation (symptoms and/or imaging). Patients were excluded if serology was weakly positive and another diagnosis more likely. Personal data, laboratory results, imaging, proposed treatment and outcome were collected from patient files. Sixty patients had a positive serology during this time period. Forty-seven of them had a more plausible alternative diagnosis and were not included in the study, leaving 13 patients for analyses; 46.2% (6/13) were male, mean age was 45.8 years old (range, 17-80 years old). Four patients (4/13, 30.8%) were asymptomatic, nine (9/13, 69.2%) presented with symptoms ranging from right upper quadrant abdominal pain (44.4%) and generalized pruritus (33.3%) to weight loss and night sweats (33.3%). The mean duration of symptoms until correct diagnosis was 8.9 months (range, 1-48 months). Five patients (5/13, 38.5%) had documented eosinophilia, four (4/13, 30.8%) elevated liver enzymes and seven (7/13, 53.8%) elevated cholestasis parameters. Mean antibody level on serology was 88 AU/mL (range, 3-134 AU/mL). Ultrasound was used most frequently (7/13, 53.8%), followed by magnetic resonance imaging (4/13, 30.8%), computed tomography and endoscopic retrograde cholangiopancreatography (3/13, 23.1%). The most common findings were bile duct dilatation, followed by hepatic lesions. Treatment consisted of Triclabendazole 10 mg/Kg. One patient needed a second treatment course for persistent disease. There were no recurrences. With a low incidence of Fasciola hepatica in Switzerland, correct diagnosis is often substantially delayed. Raising awareness among Swiss physicians is paramount, and a higher level of suspicion necessary when confronted with unspecific symptoms or liver imaging, thus avoiding a long delay in diagnosis, as well as unnecessary tests.

Relationship of Serum Antileishmanial Antibody With Development of Visceral Leishmaniasis, Post-kala-azar Dermal Leishmaniasis and Visceral Leishmaniasis Relapse.

IntroductionTo sustain the achievement of kala-azar elimination program (KEP), early detection and treatment of the visceral leishmaniasis (VL) cases and associated modalities such as treatment failure (TF), relapse VL (RVL), and Post-kala-azar dermal leishmaniasis (PKDL) is the cornerstone. A predictive biomarker for VL development and related complications could also play a crucial role in curtailing disease incidence and transmission. Investigations to find a biomarker with prospective capabilities are, however, scarce. Using samples and known clinical outcomes generated within two previous longitudinal cohort studies, we aimed to determine if fluctuations in serum anti-rK39 antibody levels could provide such predictive value.Materials and MethodsSerum samples collected at four different time points (Baseline, 12, 18, and 24 months) from 16 patients who had developed VL within the monitoring period and 15 of their asymptomatic healthy controls counterparts were investigated. To investigate potential prediction of VL related complications, serum samples of 32 PKDL, 10 RVL, 07 TF, and 38 cured VL from a single dose AmBisome trial were analyzed. Of this second panel, all patients were monitored for 5 years and sera were collected at four time points (Baseline then 1, 6, and 12 months after treatment). The level of anti-rK39 antibodies in archived samples was measured by a semi-quantitative ELISA.ResultsThe mean antibody level was significantly higher in VL patients compared to their asymptomatic healthy counterparts at each time point. Likewise, we observed a trend toward elevations in antibody levels for PKDL, RVL, TF relative to the reducing levels observed in cured VL. Receiver operating characteristic (ROC) analysis found a promising predictive power of rK39 antibody levels to reveal progression from asymptomatic Leishmania donovani infection stage to VL, defined as 87.5% sensitive and 95% specific. Following treatment, rk39 antibody notably showed 100% sensitivity and 95% specificity in predicting TF.ConclusionOur data indicate that the relative quantity of serum anti-rK39 antibody has promise within either a predictive or prognostic algorithm for VL and VL-related modalities. These could enable VL control programs to implement more effective measures to eliminate the disease. Further research is, however, imperative to standardize the rK39 antibody ELISA between sites prior to broader use.

Serological responses of Australian horses using a commercial duplex indirect ELISA following vaccination against strangles.

To determine the nature of serological responses in Australian horses using a commercial duplex indirect ELISA (iELISA) following vaccination against strangles. A group (n = 19) of client-owned horses from five properties were recruited to receive a primary course of a Streptococcus equi subsp. equi (S. equi) extract vaccine. Serological responses were determined by duplex iELISA incorporating S. equi-specific fragments of two cell wall proteins, SEQ2190 and SeM (antigens (Ag) A and C, respectively). The horses were administered a primary strangles vaccination course. Blood was collected immediately prior to each of the three vaccinations at 2-week intervals and additionally at 28 and 56 days following the 3rd vaccination (V3). Significant increases in mean antibody levels of horses following vaccination were limited only to AgC, which was significantly increased at T2/V3, 14 days following V2 (ratio of geometric means = 3.7; 95% confidence interval (CI): 1.6, 8.4; P = 0.003). There was no increase in mean antibody to Ag A (ratio of geometric means = 1.4; 95% CI: 0.6, 3.2; P = 0.39). Four horses (22%) exceeded the test cut-off for AgC following vaccination. Vaccination of Australian horses is unlikely to interfere greatly with detection of strangles using the duplex iELISA. No responses would be anticipated to AgA following vaccination with Equivac© S/Equivac© 2in1 and only a minority are likely to respond to AgC. We conclude that the results of this study validate the usefulness of the duplex iELISA to assist control measures for strangles outbreaks in Australian horse populations.

Serum antibodies against Toxoplasma gondii and Neospora caninum in southeast Queensland dugongs

AbstractThe dugong (Dugong dugon) is an herbivorous marine mammal that inhabits tropical inshore waters and thus may be vulnerable to pollutants and terrestrial pathogens as a result of coastal runoff. In this study, serum samples collected from live, wild dugongs (n = 114) in an embayment located on the urbanized southeast Queensland coast of Australia during 2008–2014, were measured for IgG antibody levels specific to Toxoplasma gondii and Neospora caninum. An ELISA used to measure T. gondii tachyzoite antibodies indicated a non‐Gaussian distribution of antibody level, with five dugongs identified as high outliers. Mean levels of antibodies specific for T. gondii in dugongs sampled in 2014 were significantly higher than in 2010 (p = .006) and 2011 (p = .009) with an elevation in mean antibody levels after a major 2011 flood event relative to antibody levels prior to the flood (p &lt; .0001). A competitive ELISA to detect N. caninum antibody indicated a normal distribution of antibody with no high outliers. Mean antibody level for N. caninum was highest in 2012 and declined significantly in 2014 (p = .004). This is the first survey of antibodies directed against T. gondii and N. caninum in dugongs and suggests future health monitoring of this species.

Effects of Polymorphisms in the SjSP-13 Gene of Schistosoma japonicum on Its Diagnostic Efficacy and Immunogenicity

Schistosomiasis japonica is one of the most prevalent parasitic diseases in China. The scarcity of effective diagnostic tools is a major factor that contributes to the high prevalence of schistosomiasis japonica. SjSP-13 is a promising serological diagnostic biomarker of the disease. However, it is unclear whether polymorphisms in SjSP-13 affect its diagnostic efficacy and immunogenicity. Here, we found the SjSP-13 gene was highly polymorphic, and all the alleles of the gene were clustered into two clades, clade A and B. SjSP-13.6 and SjSP-13.25, the representative alleles of clade A and B, were produced in Escherichia coli. The diagnostic value of SjSP-13.6 (AUC = 0.983 ± 0.006), was found to be similar to the SjSP-13.25 (AUC = 0.973 ± 0.009) by receiver operating characteristic (ROC) analysis. SjSP-13.6 and SjSP-13.25 have the same specificity (96.7%), while the sensitivity of SjSP-13.6 (90.4%) is slightly but not significantly higher than SjSP-13.25 (85.2%). The combination use of the two alleles (SjSP-13.6/25) didn’t increase the diagnostic performance of SjSP-13 as the AUC value of SjSP-13.6/25 is 0.977 ± 0.009, lower than individual SjSP-13.6 (AUC = 0.983 ± 0.006). In addition, we found the immunogenicity of clade A alleles is significantly higher than clade B in Schistosoma japonicum naturally infected animals and patients, as the mean antibody levels of SjSP-13.6 was significantly higher than SjSP-13.25. We conclude that polymorphisms of the SjSP-13 gene should not affect its diagnostic efficacy, and it is not necessary to combine the alleles of the two clades for diagnosis of schistosomiasis.

Anti-polysaccharide and anti-diphtheria protective antibodies after 13-valent pneumococcal conjugate vaccination in rheumatoid arthritis patients under immunosuppressive therapy

Immunogenicity of 13-valent pneumococcal polysaccharide (PnPS) conjugate vaccine (PCV13) was evaluated in 38 rheumatoid arthritis patients under immunosuppressive treatment and 20 healthy controls (HC). Antibodies to all PnPS and diphtheria-toxin analogue conjugate protein were measured pre- (T0), 1 (T1), 6 (T2), 12 (T3) months post-immunization. Patients and HC had similar response to individual PnPS. Mean antibody levels to all PnPS but one doubled at T1 compared with T0, with T3 persistence for only 8-7/13 PnPS. Baseline antibody levels was inversely associated with the rate of responders at T1 (T1/T0≥2) to 11/13 PnPS. Few subjects reached protective IgG levels against some serotypes frequently isolated in Italian patients with invasive pneumococcal disease. Antibody response was not influenced by therapy, except the one to PS7F, which was reduced by tumor necrosis factor-α-inhibitors. Vaccination increased also anti-diphtheria IgG. Despite this study substantially confirmed the PCV13 immunogenicity in immunocompromised patients, it also revealed some limitations.

Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer

BackgroundResected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively.MethodsPre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival.ResultsPrior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p = 0.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR = 0.23; p = 0.04).ConclusionsThese results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting.Trial registrationClinicalTrials.gov, NCT00005970. Registered on July 5, 2000.

Evaluation of Some Immunological Marker for Early Diagnosis of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic,destructive autoimmune disease affecting the joints. With more sophisticated and effective therapies becoming available and with the understanding that early intervention is crucial in preventing irreversible joint damage,it is more and more important to diagnose RA at a very early stage in the disease. To facilitate diagnosis during the early stages of the disease,when often not all clinical symptoms are manifest,a good serological marker is needed. The main purpose of this observational study was to evaluate and detects a good serological marker and genetic factors may be used in early detection of RA. This study covers quite different regions of Najaf province,including rural and urban communities. During the period from May 2010 to May2011,a total of 40 patients with RA who were fulfilled four or more of the 1987 American College of Rheumatology (ACR),20 patients with joints problems (JP),20 RA patient relatives (PR) and 10 apparently healthy control individuals were included in this study. Cytokines (interleukin-1,IL-6,IL-10 and TNF ɑ),antibodies directed to cyclic citrullinated peptide (anti-CCP3),and anti-human immunoglobulin binding protein (anti-BiP) antibodies in the human serum samples were measured by enzyme-linked immunosorbent assay (ELISA). Thirty-two RA patients (80.0%) were positive for anti-CCP3,whereas only 20.0%,30.0% and 0.0% showed a positive reaction,in particular sera from PR,JP and healthy control,respectively with highly significant difference was observed. The mean serum anti-CCP3 antibody level was higher in RA patients than in other groups. The anti-BiP antibody levels were significantly increased in RA patients than in PR and healthy control. However,the levels of anti-BiP antibody were slightly increased in the JP and no significant difference was detected between RA patients and JP. Analysis of the serum samples showed that concentrations of the Proinflammatory cytokines,IL-1,IL-6 and TNFɑ were significantly increased in RA patients compared with matched control subjects. While,The level of IL-10 was significantly lower for RA patients than for healthy Control cases.

RELATIONSHIP OF SERUM DIPEPTIDYL PEPTIDASE-IV ACTIVITY AND ANTI-CASEIN ANTIBODIES TO GASTROINTESTINAL SYMPTOMS AMONG CHILDREN WITH AUTISM SPECTRUM DISORDER: AN EGYPTIAN STUDY

Objectives: The objectives of the study were to assess serum dipeptidyl peptidase-IV (DPP-IV) activity in autistic children suffering from severe gastrointestinal (GI) disorder and to examine the hypothesis that there is a link between DPP-IV activity in serum and GI disorder in a subgroup of children with autism spectrum disorder (ASD).Subjects and Methods: Serum levels of casein antibodies and DPP-IV enzyme activity from 40 autistic children with chronic GI symptoms, and 40 of age-matched children without autism or gastrointestinal (GI) symptoms were assayed using enzyme-linked immunosorbent assay kits.Results: In comparison with controls, developmental milestones were delayed among autistic children. The serum DPP-IV activity was significantly lower in the studied patients (p&lt;0.05), while the mean serum levels of casein antibodies were statistically significantly higher in the studied patients (p&lt;0.01). Multiple logistic regression analysis recorded significant association between the high serum level of antibodies to casein, food selectivity and recurrent attacks of abdominal pain (p&lt;0.05), while the low serum DPP-IV enzyme activity was associated with recurrent attacks of abdominal pain in the studied patients with a prediction of 95% (p&lt;0.05).Conclusions: Serum levels of casein antibodies were higher in children with ASD, and maybe contributes to their abdominal pain, and food selectivity. Serum DPP-IV enzyme activity was lower and associated with recurrent attacks of abdominal pain in the studied patients. They may benefit from a supplemental digestive enzyme formula.

Significance of Anti-Myosin Antibody Formation in Patients With Myocardial Infarction: A Prospective Observational Study

Anti-myosin antibodies (AMAs) are often formed in response to myocardial infarction (MI) and have been implicated in maladaptive cardiac remodelling. We aimed to: (1) compare AMA formation in patients with Non-ST-Elevation MI (NSTEMI) and ST-Elevation MI (STEMI); (2) evaluate factors predicting autoantibody formation; and, (3) explore their functional significance. Immunoglobulin M (IgM) and Immunoglobulin G (IgG) AMA titres were determined in serum samples collected at admission, 3 and 6 months post MI. The relationship between demographic and clinical data, and antibody formation, was investigated to determine factors predicting antibody formation and functional significance. Forty-three (43) patients were consecutively recruited; 74.4% were positive for IgM at admission, compared with 23.3% for IgG. Mean IgG levels increased by 1.24% (±0.28) at 3 months, and 13.55% (±0.13) at 6 months post MI. Mean antibody levels were significantly higher in the NSTEMI cohort at both follow-up time points for IgG (p<0.001, p<0.0001), but not IgM (p=0.910, p=0.066). A moderately positive correlation between infarct size and increase in mean IgM concentration was observed at 3 months (r(98)=0.455; p=0.015). Anti-myosin antibody formation was not associated with an unfavourable outcome at follow-up. Anti-myosin antibodies are formed in a significant proportion of patients following MI, particularly among those with NSTEMI. While IgM levels fall after infarction, IgG levels increase and persist beyond 6 months of follow-up. This raises the possibility that they may contribute to long-term myocardial damage and dysfunction. Future research should focus on the specific epitopes that are targeted by these antibodies, and their functional significance. This may result in the emergence of novel therapies to attenuate cardiac dysfunction in MI patients.

Antinucleosome Antibody in Children and Adolescents with Systemic Lupus Erythematosus

AbstractBackground: SLE is an autoimmune disease of unknown etiology characterized by the production of abroad and heter-ogeneous group of autoantibodies. These autoantibodies are directed to nuclear, cytoplasmic, and cellular membrane antigens. Recently, it was proposed that the nucleosome is the principal antigen in the pathophysiology of SLE, and that anti-Nuc antibodies are associated with organic damage.Aim of the Study: The aim of this work was to study the potential utility of serum levels of anti- nucleosome antibodies as a diagnostic tool and a disease activity marker in children and adolescents with systemic lupus erythematosus.Patients and Methods: The study was carried out on forty five patients with SLE who attended to the outpatient clinic and inpatient of Pediatric Nephrology matched age and sex served as a control group. All studied children were subjected to full history, complete physical examination, SLEDAI score, routine laboratory investigations and anti-dsDNA and anti-nucleosome antibody IgG assay. Data was analyzed by using SPSS.Results: The mean serum level of anti-Nuc antibody was significantly higher in patients than controls (p-value <0.001). But there was no significant difference between patients' subgroups. There was a weak correlation between serum anti-Nuc antibody and SLEDAI score (r: 0.213) but strong corre-lation between anti-dsDNA antibody and SLEDAI score (r: 0.711). Anti-Nuc antibody showed higher sensitivity but equal specificity to anti-dsDNA antibody for the diagnosis of SLE.Conclusion: Anti-nucleosome antibodies are superior to anti-dsDNA antibodies in the diagnosis of SLE especially in anti-dsDNA negative patients as they have higher sensitivity but as regard to disease activity antidsDNA antibody is more accurate.

Neural autoantibodies in patients with neurological symptoms and histories of chemical/mold exposures.

A number of studies have linked exposures to industrial and household chemicals and biological toxins to increased risk of autoimmunity in general and elevated levels of autoantibodies to neural antigens specifically. Elevated neural autoantibodies are biomarkers for many diseases such as multiple sclerosis and Parkinson's disease. Our study reports levels of six types of neural autoantibodies in a group of 24 toxicant-exposed patients. The patients were exposed to a variety of toxicants including contaminated drinking water (four patients), building water/mold damage (eight patients), pesticides (four patients), and other assorted toxic chemicals (eight patients). Levels of all six neural autoantibodies were significantly elevated in most patients and in the patient group at large, with mean antibody levels for the 24 chemically exposed patients (relative to a healthy control population), in descending order: 475% for tau proteins, 391% for microtubule associated proteins-2, 334% for neurofilament proteins (NFP), 302% for myelin basic protein, 299% for glial fibrillary acidic proteins, and 225% for tubulin. Tau protein autoantibodies were significantly elevated in the patient groups with peripheral neuropathy, muscle and joint pain, asthma, and chemical sensitivity. Autoantibodies to tubulin were significantly higher in the chemical sensitivity and asthma patients, autoantibodies to NFP were significantly higher in the patients with sleep apnea, whereas S-100B autoantibodies were significantly increased in patients with muscle/joint pain, asthma, and apnea/insomnia. In patients exposed to environmental toxicants, measurements of autoantibodies may be useful for prevention, diagnosis, and treatment. This study adds to the scientific literature the ability of a broad spectrum of environmental triggers adversely affecting the nervous system through the process of autoimmunity, which may explain the increasing incidence of neurodegenerative diseases.

Modeling specific antibody responses to natural immunization to predict a correlate of protection against infection before commencing a clinical vaccine trial

ABSTRACT Background Clinical trials of vaccines for children to prevent acute otitis media (AOM) infections caused by the bacteria Streptococcus pneumonia (Spn) are in Phase I. The objective of this study was to use serum antibody measurements to pneumococcal purified protein candidate antigens that occurred after natural “immunization” to predict a correlate of protection response needed following an injectable vaccine against AOM in children. Methods 590 nasal and serum samples were collected from 129 healthy children at 6, 9, 12, 15, 18, 24 and 30–36 months of age and when the child developed AOM. Middle ear fluid to detect Spn was collected at every episode of AOM. Quantitative ELISA was used to determine serum IgG against 7 Spn vaccine antigens: PspA clade 3, PspA clade 5, PhtD, PhtE, LytB, PcpA and Ply. A correlate of protection (COP) was estimated by regressing AOM events against age adjusted antibody levels induced by nasopharyngeal colonization and AOM infections, using logistic regression and generalized estimating equation methods. Results A significant COP was found for Spn PhtD (p = 0.0015), PhtE (p = 0.00034), LytB (p = 0.004), PcpA (p = 0.002), and Ply (p = 0.007) between higher antibody levels and reduced frequency of AOM. We estimated that a 2-fold higher antibody level in a child than the mean antibody level induced by NP colonization (after adjusting for subject age) to PhtD, LytB, PcpA, PhtE or Ply reduced the risk of AOM by 14–21%, a 4-fold higher level reduced it by 25–38% and a 10-fold higher level reduced it by 39–54%. Conclusion We developed a model to predict the necessary level of serum antibody and fold higher above a threshold to PhtD, PhtE, LytB, PcpA and Ply that would correlate with a reduced likelihood of AOM in children age 6–24 months old if enrolled in a Phase III clinical efficacy trial.

Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer.

The anaplastic lymphoma kinase (ALK) is recognized by the immune system as a tumor antigen, and preclinical evidence suggests that ALK-rearranged NSCLCs can also be successfully targeted immunologically using vaccine-based approaches. In contrast to ALK-rearranged lymphomas, the frequency and clinical significance of spontaneous ALK immune responses in patients with ALK-rearranged NSCLCs are largely unknown. We developed an enzyme-linked immunosorbent assay (ELISA) to measure anti-ALK antibody levels and mapped specific peptide epitope sequences within the ALK cytoplasmic domain in patients with non-small cell lung cancer. The ELISA method showed good correlation with ALK antibody titers measured with a standard immunocytochemical approach. Strong anti-ALK antibody responses were detected in 9 of 53 (17.0%) ALK-positive NSCLC patients and in 0 of 38 (0%) ALK-negative NSCLC patients (P<0.01), and the mean antibody levels were significantly higher in ALK-positive than in ALK-negative NSCLC patients (P=0.02). Across individual patients, autoantibodies recognized different epitopes in the ALK cytoplasmic domain, most of which clustered outside the tyrosine kinase domain. Whether the presence of high ALK autoantibody levels confers a more favorable prognosis in this patient population warrants further investigation.

A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections.

This review aims to evaluate the literature on the safety and efficacy of novel toxoid vaccines for the prophylaxis of Clostridium difficile infections (CDI) in healthy adults. Literature searches for clinical trials were performed through MEDLINE, ClinicalTrials.gov, and Web of Science using the keywords bacterial vaccines, Clostridium difficile, and vaccine. English-language clinical trials evaluating the efficacy and/or safety of Clostridium difficile toxoid vaccines that were completed and had results posted on ClinicalTrials.gov or in a published journal article were included. Six clinical trials were included. The vaccines were associated with mild self-reported adverse reactions, most commonly injection site reactions and flu-like symptoms, and minimal serious adverse events. Five clinical trials found marked increases in antibody production in vaccinated participants following each dose of the vaccine. Clinical trials evaluating C. difficile toxoid vaccines have shown them to be well tolerated and relatively safe. Surrogate markers of efficacy (seroconversion and geometric mean antibody levels) have shown significant immune responses to a vaccination series in healthy adults, indicating that they have the potential to be used as prophylaxis for CDI. However, more research is needed to determine the clinical benefits of the vaccines.

Anti -citrullinated peptide antibodies profiling in established rheumatoid arthritis

ObjectivesAnti-citrullinated protein/peptide antibodies (ACPA) represent an important tool for the diagnosis of rheumatoid arthritis (RA) and the presence of multiple ACPA specificities is highly correlated with the evolution towards RA. However, little is known about the association of single specificities with disease manifestations and response to therapy in established RA. The aim of this work is to evaluate in a retrospective study the clinico-serological association of ACPA detected using VCP1 and VCP2 (EBV-derived citrullinated peptides) and HCP1 and HCP2 (histone-H4-derived citrulinated peptides) in established RA. MethodsIn 413 RA patients, anti-VCP1, -VCP2, -HCP1, -HCP2 were measured by ELISA. Patients were evaluated for systemic involvement, disease activity/severity, ongoing and past therapies. Data were analyzed by cluster analysis (CA) and principal component analysis (PCA). ResultsAnti-VCP1 were detected in 44% of RA patients; anti-VCP2 in 52%; anti-HCP1 in 46% and anti-HCP2 in 63%. CA and PCA independently demonstrated that ACPA levels are associated with RF positivity, and lung involvement. Subdividing patients in 5 groups according to the number of anti-peptide antibodies, mean antibody level and RF positivity, as well as the frequency of lung involvement, progressively increase in parallel with the number of ACPA specificities. ConclusionsHigher number/levels of ACPA subtypes is associated with lung involvement but not with erosive disease. Moreover, a broader ACPA repertoire may identify patients treated with biological therapy, probably affected by a more severe disease. In conclusion, ACPA typing might be relevant for a better characterization of some disease features in established RA.

Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels.

BackgroundSerological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays.Methods/Principal findingsWe developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P. falciparum (Spearman’s rho = 0.75). In both high- and low transmission settings, mean antibody curves revealed changes in population mean antibody levels that were masked by seroprevalence measures because changes took place above or below the seropositivity cutoff.Conclusions/SignificanceAge-dependent antibody curves and summary means provided a robust and sensitive measure of changes in transmission, with greatest sensitivity among young children. The method generalizes to pathogens that can be measured in high-throughput, multiplex serological assays, and scales to surveillance activities that require high spatiotemporal resolution. Our results suggest quantitative antibody levels will be particularly useful to measure differences in exposure for pathogens that elicit a transient antibody response or for monitoring populations with very high- or very low transmission, when seroprevalence is less informative. The approach represents a new opportunity to conduct integrated serological surveillance for neglected tropical diseases, malaria, and other infectious diseases with well-defined antigen targets.