Ab Levels Research Articles

N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia.

Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia. We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay. The FES group showed higher serum NMDAR Ab levels [(9.23 ± 4.15) ng/mL vs. (7.08 ± 2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference). Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

8426 Recurrence of Papillary Thyroid Carcinoma Despite Undetectable Levels of Thyroglobulin Measured by Both Immunoassay and LCMS

Abstract Disclosure: M.G. Hamilton: None. G. Patel: None. S. Teja Sathi: None. K. Win: None. P. Lekprasert: None. Serum thyroglobulin (Tg) levels are affected by the presence of anti-thyroglobulin antibodies (anti-Tg Abs) during surveillance of differentiated thyroid cancer (DTC). About 20% of patients have positive anti-Tg Abs post-thyroidectomy and laboratory investigations for DTC surveillance may lead to false negative results. Liquid chromatography-tandem mass spectrometry (LCMS) is superior to immunoassay in measuring Tg levels in patients with the presence of anti-Tg Abs. Mass spectrometry is the only currently available method that could eliminate the interference of anti-Tg Abs in the quantification of Tg but is not readily available. We present the case of a patient who had a recurrence of DTC despite persistently undetectable Tg levels using both immunoassay and LCMS methods. The patient is a 49-year-old female with a history of papillary thyroid cancer who underwent total thyroidectomy followed by adjuvant radio-ablation. She presented to our endocrinology office for routine follow up for her DTC. She reported subjective unknown weight loss over four months. Her physical exam was unremarkable with no palpable neck swelling or mass. Vital signs were within normal limits. She continued to have undetectable levels of Tg as measured by immunoassay, stable levels of anti-Tg Abs ranging from 19 IU/mL to 33 IU/mL, and negative findings on her thyroid ultrasound for the first four years post-op. When she presented to the office five years post-thyroidectomy her anti-Tg Ab level had increased to 114 IU/mL and subsequently to 137 IU/mL a few months later despite undetectable Tg levels on both immunoassay and LCMS. A thyroid ultrasound was completed due to rising anti-Tg Abs levels which showed a suspicious one cm mass at the right thyroid bed and suspicious bilateral cervical lymph nodes. Repeated FNA biopsy of the bilateral cervical lymph nodes confirmed follicular epithelium with nuclear inclusions and grooves, compatible with recurrent papillary thyroid carcinoma. This patient had a recurrence of her DTC despite undetectable Tg levels on both immunoassay and LCMS. Tg is an important aspect of surveillance post-treatment for all patients with DTC because its presence is a surrogate for the presence of thyroid tissue and therefore the recurrence of thyroid malignancy. Clinicians must have a high index of suspicion when monitoring a patient with a history of DTC and the presence of anti-Tg Abs because it interferes with the accurate measurement of Tg levels. A study conducted by Azmat et al. demonstrated that measuring Tg levels via LCMS has been found to eliminate the confounding effect of anti-Tg Abs with a sensitivity and specificity of 44.4% and 94.1% respectively. However, our case illustrates that even LCMS is not always reliable in such situations, and increasing levels of anti-Tg Abs should be an individual risk factor for suspecting recurrence of DTC. Presentation: 6/3/2024

B-266 Therapeutic Drug Monitoring of Natalizumab and Anti-Natalizumab Antibodies

Abstract Background Natalizumab (NTZ) is a monoclonal antibody directed against the α4-integrin subunit of α4β1 and α4β7 integrins. NTZ is used to treat relapsing and remitting forms of multiple sclerosis. Although a majority of patients on standard dosing (intravenous 300 mg, every 4 weeks) reach therapeutic drug concentrations, about 10% of patients will eventually fail NTZ therapy due to the development of anti-NTZ antibodies. NTZ and anti-NTZ antibody concentrations in serum are used together to provide patient-specific pharmacokinetic and immunogenic assessment to aid in patient management. Methods Serum measurements of NTZ and anti-NTZ antibody levels are performed by lab developed electro-chemiluminescent immunoassays where assay design and principle are equivalent to biologic therapeutic drug monitoring described in our previous publication. The natalizumab drug assay is an immunoassay validated to measure free drug (pharmacodynamically active, ADA-unbound) in serum. The anti-natalizumab antibody assay utilizes a solution phase bridging method designed to measure total binding antibodies (including IgM & IgG subtypes). All anti-natalizumab antibody positive samples are confirmed for drug-specificity by an additional signal suppression step. The anti-natalizumab antibody assay is quantitative and drug-tolerant, meaning that circulating drug in patient serum does not interfere with anti-NTZ detection and quantitation. Results Here, we report concomitant measurement of NTZ and anti-NTZ antibody in 160 patient serum samples. Positive anti-NTZ levels from 24 to 235 ng/mL were found in 7.5% (12/160) patients. Anti-NTZ-free samples (148/160) had NTZ drug levels ranging from undetectable (<1.0) to 85 ug/mL. The mean and median drug level in 90 samples (results >1.0) was 10.8 and 2.7, respectively. 61/90 samples had therapeutic drug concentrations (at least 2.0 ug/mL). In the presence of anti-NTZ, 67% (8/12) had undetectable drug level and (4/12) had mean and median drug levels of 1.2 and 1.3, respectively, which is 9- or 2-fold lower than the mean and median drug levels of the anti-NTZ Ab -free group. Conclusions Low serum NTZ and high anti-NTZ are associated with loss of clinical efficacy, while elevated NTZ may increase progressive multifocal leukoencephalopathy risk. Assays to measure biologic drugs and their anti-drug antibodies in patient serum may be useful tools in dose optimization and patient management.

Unique Kinetics of the Human Milk Antibody Response to JYNNEOS Vaccine for Prevention of Monkey Pox: A Case Study.

Background: JYNNEOS is a nonreplicating modified vaccinia Ankara vaccine currently licensed to prevent monkeypox infection, and its milk immunogenicity remains unstudied. Objective: Investigate the human milk immunogenicity of the JYNNEOS vaccine in one individual and examine the milk for evidence of vaccine components. Methods: Immunogenicity of milk and plasma samples were tested by Luminex assays against Vaccinia antigens, and vaccine components were tested using PCR and sandwich ELISA. Results: Plasma antibody (Ab) response increased up to 3.7-fold in immunoglobulin G (IgG) titer and 1.4-fold in IgA compared with baseline, confirming vaccine immunogenicity in this participant 2 weeks post dose 2. Specific plasma IgG remained 1.2- to 1.7-fold above baseline 12 weeks post dose 2, while IgA returned to baseline levels. Notably, the milk response exhibited unique kinetics, particularly for IgA. Milk IgA against all three antigens increased 0.9- to 2.2-fold 2 weeks post dose 2, reaching a peak titer increase of 1.1- to 2.7-fold at 12 weeks post dose 2. Secretory (s) Ab levels increased to 1.1- to 2-fold at 2 weeks post dose 2 and reached a peak of 2- to 3.2-fold increase at the 12-week time point. Importantly, IgA and sAb responses in milk exhibited correlation, suggesting most milk IgA was sIgA. Notably, no vaccine components (VACV protein or DNA) were detected in the milk samples. Conclusion: These data suggest that the milk Ab response to this intradermal (ID) VACV-based vaccine is distinct from that observed systemically, indicating a unique mucosal immune response and highlighting its potential to elicit protective long-lasting sIgA. This case report provides strong evidence for inclusion of this vaccine platform in future studies of maternal vaccines aimed to elicit a protective milk Ab response.

Erythema nodosum manifestation of Parvovirus B19-associated reactive arthritis.

Parvovirus B19 virus-mediated viral inflammation and immune-complex deposition generate mainly short-term manifestations in the affected individuals. The objective of this study was to determine Parvovirus B19 infection in rheumatoid arthritis (RA) patients. The study employed 50 patients diagnosed with RA and 30 healthy individuals. Blood samples were collected from both groups. The blood samples were screened for Parvovirus B19 infection using polymerase chain reaction to detect B19 DNA and enzyme-linked immunosorbent assay to detect anti-B19 IgM and IgG. 17 (34%) of 50 patients tested positive for parvovirus B19 DNA. In contrast, the mortality rate in the control group was significantly lower (6.7%; p = 0.005). Anti-B19 IgG antibody levels differed significantly with patients and control (p = 0.007), whereas anti-B19 IgM Ab levels did not (p = 0.6). There was a significant correlation between viremia B19 and all measured parameters. Parvovirus-affected patients had significantly higher CRP and ESR, elevated DAS28 scores, and more joint pain compared to parvovirus (-) patients. Anti-CCP and RF values were significantly high in parvovirus (+) patients. Joint erosion was also prevalent in patients who tested positive for parvovirus. The findings of this study suggest that infection with parvovirus in patients with RA, and a possible role of this viral infection in the pathogenesis of RA may contribute to the pathogenesis of RA.

Proportion and Covariates of Hypothyroidism Among Patients with Metabolic Syndrome Attending in Tertiary Care Hospital

Background: Hypothyroidism in patients with metabolic syndrome is associated with worse outcomes. However, this has not yet been adequately investigated in Bangladeshi people. Objective: To find out the proportion and covariates of hypothyroidism among patients with metabolic syndrome. Materials and methods: A hospital-based cross-sectional study was conducted with 323 patients from the Endocrinology and Allied Medicine Department at BIRDEM General Hospital. Patients with metabolic syndrome but no prior diagnosis of hypothyroidism were included. Detailed history, physical examinations, and thyroid function tests—Thyroid Stimulating Hormone (TSH), Free Thyroxine (FT4), and Anti-Thyroid Peroxidase Antibody (Anti-TPO Ab)—were performed. Subclinical hypothyroidism was defined as TSH >4.12 mIU/L and <10 mIU/L, while overt hypothyroidism was defined as TSH >10 mIU/L. Statistical analyses, including Chi-square tests, ANOVA, Pearson's correlation, and multiple linear regression, were conducted to explore associations between components of metabolic syndrome and thyroid dysfunction. Results: Out of the 323 participants, 62.8% were euthyroid, 28.5% had subclinical hypothyroidism, and 8.7% had overt hypothyroidism. Autoimmune hypothyroidism was confirmed in 31.6% of hypothyroid patients through elevated Anti-TPO Ab levels, a statistically significant finding. Hypothyroidism was significantly more prevalent in females and obese individuals. Significant positive correlations were observed between TSH and waist circumference (r=0.153), systolic blood pressure (r=0.271), and triglycerides (r=0.128), while FT4 showed negative correlations. Multiple linear regression indicated significant associations between waist circumference, fasting plasma glucose, and thyroid dysfunction. Conclusion: It was concluded that a higher proportion of metabolic syndrome cases were suffering from hypothyroidism. This necessitates that all MetS patients be screened for thyroid profile and autoimmune status and managed accordingly.

Effect of intravenous methylprednisolone on serum antibody levels in thyroid eye disease

Background/aimsWe evaluated longitudinal autoantibody changes after intravenous methylprednisolone (IVMP), compared them with those in untreated patients and identified prognostic factors for treatment response.MethodsIn this single-centre, retrospective, observational study, a total...

Primary Membranous Nephropathy Flare After COVID-19 Vaccination

Primary membranous nephropathy (MN) is due to autoantibodies to phospholipase A2 receptor (PLA2R Ab). It is unclear whether COVID-19 vaccines can trigger flares of glomerular diseases such as primary MN. There have been increasing reports of glomerular diseases presenting or flaring after receipt of COVID-19 vaccines. We present a patient with primary MN who developed nephrotic syndrome after receiving her second mRNA-1273 COVID-19 vaccine with positive PLA2R Ab. Renal biopsy confirmed primary MN. She was treated for her primary MN flare with rituximab in a manner similar to non-vaccine-associated MN, which led to significant reduction in both PLA2R Ab level and proteinuria. This case adds to the growing literature on MN flares after receipt of mRNA COVID-19 vaccines. Close follow-up of patients with primary MN and other glomerular diseases after COVID-19 vaccination is warranted. Further research is needed to determine the pathophysiology behind vaccine-induced MN flares and whether there is a potential association between exposure to SARS-CoV-2 antigens and loss of tolerance to the PLA2R antigen.

SARS-COV-2 breakthrough infection and its covariates among healthcare providers of a hospital in Bangladesh during the omicron wave

IntroductionBreakthrough infection by SARS-COV-2 virus among vaccinated individuals has been reported from all over the world and it has created a substantial challenge in designing strategies to live with the virus in the post-pandemic era. Factors affecting the extent and nature of breakthrough infection are still not fully understood and those are known to vary depending on host and agent factors. Health Care Workers (HCWs), especially in hospital settings, are front-liners in combating the epidemic and, consequently, they are more vulnerable to breakthrough infection by SARS-COV-2. Like most of the countries of the world, Bangladesh went through several waves of COVID-19 and the last (3rd wave) was the widespread Omicron wave during the winter of 2022. HCWs in Bangladesh have been disproportionately affected by the virus. Under this context, the aim of the present study was to explore breakthrough infection (BTI) and its host-related covariates among HCWs of a COVID-dedicated city-based hospital during the Omicron wave in Bangladesh. Materials and methodsAn observational cross-sectional study was conducted on 267 HCWs of the Narayanganj Tertiary (300-bed) hospital during February–March 2022 which coincided with the terminal part of the 3rd wave. Data were collected by trained Field Assistants using Interviewer-administered Data Collection Forms with Questionnaires as instruments. Previous COVID-19 status (any time after the onset of the pandemic and within last 3 months) was explored by the history of specific symptoms as well as by the confirmatory rtPCR test reports from DGHS approved laboratories Anti-nucleocapsid antibody (Anti-N-Ab) in venous blood samples, assayed by a chemiluminescent ELISA technique, was used as a seroprevalence-based marker of breakthrough infection during the preceding few months. Data were analyzed by bivariate as well as multivariate statistics using the IBM-SPSS software. ResultsThe median age (range) of the HCWs was 38 (21–65) years; Body Mass Index (BMI, kg/m2) 25 (15–49); and Waist-Hip Ratio (WHR) was 0.92 (0.46–1.21). The male subjects had significantly higher median age (p = 0.01) and higher WHR (p = 0.001) as compared to the female subjects. As per the BMI category, subjects with overweight and obesity constituted 83.3 % of the male subjects as compared to 61.6 % of the female subjects (p = 0.001). The time lapse between receiving of 3rd dose and blood sampling was significantly higher among females compared to males (median days 60 vs 49, p < 0.02) indicating earlier vaccination with 1st booster dose among females. A proportion of 51.85 % male and 49.68 % female subjects showed Anti-N-Ab positivity; there was no significant difference between the gender groups. Also, there was no significant difference among male and female subjects regarding the Ab levels. On Spearman correlation analysis, a tendency of association of WHR with Ab level was observed among the male subjects; however, the association did not show statistical significance (p = 0.09). On binary logistic regression Ab positivity was found to be independently associated with WHR (p = 0.03), and prior SARS-COV-2 infection within the last 3 months (p = 0.02) among males. When all the subjects were considered together, COVID symptom positivity during the last 3 months (p = 0.067) and receiving the 1st booster dose (p = 0.07) showed a tendency of association with Ab positivity. On multiple regression analysis, Ab levels showed a negative association with WHR (p = 0.035) among males. ConclusionsMore than 50 % of the vaccinated hospital-based HCWs in Bangladesh suffered from BTI during the winter of 2022 when the Omicron wave (the 3rd wave) of COVID-19 was at its peak. The data also indicate that overweight and obesity are major host-related risk factors underlying BTI. Inadequate coverage by a booster dose seems to be another determinant of BTI and the level of immune response in this population.

Neutrophils impaired by anti-galectin-3 antibodies elicit inflammation of endothelial cells to aggregate the development of lupus cutaneous vasculitis.

To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

Effect of angiotensin II type 1 receptor antibodies on graft function and survival in paediatric kidney transplant recipients.

HLA donor specific antibodies (DSA) are implicated in antibody-mediated rejection (AMR), graft dysfunction and failure in kidney transplant (KT) recipients. Non-HLA antibodies including angiotensin II type 1 receptor (AT1R) may also play a role in AMR, impact graft function and survival. Data is limited in paediatric KT cohorts. We aimed to assess the prevalence and effect of pre-transplant AT1R antibodies on rejection, graft function and survival in paediatric KT recipients. This was a retrospective cohort study conducted across two paediatric centres including KT recipients with a pre-transplant AT1R antibody level. Outcomes included rejection, de novo DSA formation, graft function, failure, proteinuria and hypertension. Of 71 individuals, 72% recorded a positive pre-transplant AT1R Ab level (≥17 U/mL). Over a median follow-up of 4.7 years, AT1R Ab positivity demonstrated a trend towards increased risk of rejection however was not statistically significant (HR 3.45, 95% CI 0.97-12.35, p-value 0.06). Sensitivity analysis with AT1R Ab levels of ≥25 U/mL (HR 2.05 95% CI 0.78-5.39, p-value 0.14) and ≥40 U/mL (HR 1.32, CI 95% 0.55-3.17, p-value 0.53) validated this. De novo DSA formation occurred more frequently with AT1R Ab positivity (41% vs. 20%, p-value 0.9). AT1R Ab was not associated with hypertension, proteinuria, graft failure or dysfunction. In conclusion, this cohort study demonstrated a high prevalence of pre-transplant AT1R Ab positivity (72%). AT1R Ab positivity demonstrated a trend towards increased risk of rejection and de novo DSA formation however did not meet statistical significance. There was no association between AT1R Ab and hypertension, proteinuria, graft failure or dysfunction.

Interleukin-17A (IL-17A) is involved in antibody specificity to conformational epitopes

The specificity of antibodies (Ab) is essential for the precise recognition of foreign or dangerous molecules. We have shown that mice infected with non-pathogenic Lactate Dehydrogenase Elevating Virus (LDV) inoculated with human growth hormone (hGH) or Ovalbumin (OVA), exhibit modified specificity of anti-hGH or anti-OVA Ab associated with the secretion of IFN-γ, IL-13, and IL-17.Cytokines are directly or indirectly involved in the isotypes, specificity, and affinity of Ab. Accordingly, here we investigated the effect of IL-17 neutralization on Ab specificities to OVA and Diphtheria Toxoid (DTx) in a mouse model of viral infection. Thereby, we employed an anti-cytokine “auto-vaccination” with an OVA/IL-17A complex or a Monoclonal Ab (MAb) anti-IL-17A (MM17/F3).Competitive ELISA assays were used to estimate the quality of the humoral immune response and the amount of Abs to conformational versus linear antigenic determinants. Results indicated that the OVA/IL-17A complex increased Abs levels to conformational epitopes of OVA, while LDV prolonged antibodies for a longer period. Mice treated with MM17F3 MAb showed an increase in Abs to conformational epitopes of OVA. A similar effect, confirmed by a competitive Western-blot assay, was produced by LDV. Moreover, an increased level of IgM, IgG1, and IgG2a was found in infected animals. Similarly, MAb anti-IL-17A treatment increased the proportion of Ab to conformational epitopes of DTx in uninfected mice, while LDV decreased this parameter.In conclusion, our findings demonstrate a correlation between IL-17A neutralization and a change in Ab specificity to OVA or DTx, presenting a novel strategy for obtaining Abs with higher specificity.

Frequency of seropositive celiac disease and hypothyroidism among children and adolescents with congenital heart disease: A case-control study

BackgroundThe prevalence of celiac disease (CD) and hypothyroidism exhibit significant variation in different studies among patients with congenital heart disease (CHD). This study evaluated the frequency of laboratory test abnormalities in children and adolescents with CHD in Shiraz, Iran.MethodsThis prospective case-control study was conducted on 223 children and adolescents with CHD and healthy individuals referred to the heart clinic affiliated with Shiraz University of Medical Sciences between February 2019 and December 2021. They were classified into case and control groups. Blood tests were performed for total IgA antibody, anti-tissue transglutaminase IgA antibody (anti-TTG Ab), T4, and thyroid stimulating hormone (TSH) and anti-thyroid peroxidase antibodies in serum, along with transthoracic echocardiography. Likewise, demographic characteristics of patients, including age, sex, weight, height, and body mass index (BMI), were recorded. Also, anti-TTG Ab levels were compared among CHD patients according to cyanosis status, gender, age (above and below five years), and BMI (under and over 18.5).ResultsNinety-eight CHD patients and 100 healthy individuals with an average age of 5.32 ± 4.05 years (1–18 years) were examined. In children with CHD, atrial septal defect (27%), ventricular septal defect (20%), and tetralogy of Fallot (13%) were the most prevalent disorders. Only one CHD patient had an anti-TTG Ab level of 16.6 unit/mL, considered borderline for seropositive CD diagnosis. There was no difference in anti-TTG Ab levels between age (above and below five years), BMI (under and over 18.5), cyanosis status, and gender groups. Seven CHD patients had high TSH levels, three had cyanotic CHD, and one had Down syndrome. The TSH levels and non-autoimmune hypothyroidism were significantly higher in CHD patients than in normal subjects (p < 0.05).ConclusionsAccording to the results of this study, the serum level of TSH and prevalence of non-autoimmune hypothyroidism were higher in patients with CHD than in normal subjects, but the serum level of anti-TTG Ab was not different between the two groups.

Anti-Lipoprotein Lipase Antibody as a Useful Marker for Plaque Vulnerability in Patients with Stable Angina.

Identifying patients with vulnerable plaque who have poor prognosis among those with coronary artery disease (CAD) is crucial to deciding future therapeutic interventions. We previously reported that male CAD patients with low anti-apolipoprotein B-100 autoantibody (anti-apoB-100 Ab) levels were at an increased risk of developing unstable plaque lesions. This study focused on the autoantibodies against lipoprotein lipase (LPL), a key enzyme in triglyceride metabolism, which is another risk factor for atherosclerosis, and investigated their association with plaque characteristics. We measured serum anti-LPL Ab levels using a homemade enzyme-linked immunosorbent assay in 80 male CAD patients. Coronary plaque properties were evaluated using iMAP®-intravascular ultrasound. Serum anti-LPL Ab levels were not correlated with plaque burden but were significantly negatively and positively correlated with fibrotic and necrotic plaques, respectively. High-risk patients with low anti-apoB-100 Ab levels were divided into groups according to their anti-LPL Ab levels. The group with high anti-LPL Ab levels exhibited more necrotic plaques and fewer fibrotic plaques as well as higher remnant-like lipoprotein particle levels than the group with low anti-LPL Ab levels. Serum anti-LPL Ab levels can serve as a marker of plaque instability in CAD patients and can help identify higher-risk cases when combined with anti-apoB-100 Ab levels.

Time-Dependent Effects of Clinical Interventions on SARS-CoV-2 Immunity in Patients with Lung Cancer.

In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to develop a time-dependent regression model elucidating individual contributions of factors influencing SAb levels in LC patients using a prospective, longitudinal, multi-institutional cohort study initiated in January 2021. The study evaluated 296 LC patients-median age 69; 55% female; 50% stage IV. Blood samples were collected every three months to measure SAb levels using FDA-approved ELISA. Asymptomatic and unreported infections were documented through measurement of anti-nucleocapsid Ab levels (Meso Scale Discovery). Associations between clinical characteristics and titers were evaluated using a time-dependent linear regression model with a generalized estimating equation (GEE), considering time-independent variables (age, sex, ethnicity, smoking history, histology, and stage) and time-dependent variables (booster vaccinations, SARS-CoV-2 infections, cancer treatment, steroid use, and influenza vaccination). Significant time-dependent effects increasing titer levels were observed for prior SARS-CoV-2 infection (p < 0.001) and vaccination/boosters (p < 0.001). Steroid use (p = 0.043) and chemotherapy (p = 0.033) reduced titer levels. Influenza vaccination was associated with increased SAb levels (p < 0.001), independent of SARS-CoV-2 vaccine boosters. Prior smoking significantly decreased titers in females (p = 0.001). Age showed no association with titers. This GEE-based linear regression model unveiled the nuanced impact of multiple variables on patient anti-spike Ab levels over time. After controlling for the major influences of vaccine and SARS-CoV-2 infections, chemotherapy and steroid use were found to have negatively affected titers. Smoking in females significantly decreased titers. Surprisingly, influenza vaccinations were also significantly associated, likely indirectly, with improved SARS-CoV-2 titers.

Clinical Changes and Autoantibody Level Changes in Thyroid Eye Disease Patients after Intravenous High-dose Steroid therapy

Purpose: To evaluate the effects of intravenous steroid therapy on the clinical activity score (CAS), exophthalmos, margin-reflex distance 1 (MRD1), and autoantibody levels in patients with thyroid eye disease.Methods: In this retrospective observational study, we enrolled 83 patients diagnosed with thyroid eye disease treated with intravenous steroid therapy. We assessed exophthalmos, MRD1, CAS, thyroid-stimulating antibody (TSAb), and thyroid-stimulating hormone receptor antibody (TSHR Ab) levels at baseline, 6 and 12 weeks after initiating therapy, and 2 months after therapy termination. Additionally, baseline serum selenium levels were examined to determine their impact on treatment efficacy.Results: TSAb, TSHRAb, and CAS levels showed a continuous decline from 443.22 to 341.03 specimen-to-reference control ratio (SRR%), 22.18 to 7.91 IU/L, and 3.37 to 1.88, respectively (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001), up to 2 months following therapy termination. Exophthalmos did not show significant changes at any assessed time point up to 2 months after therapy termination. MRD1 decreased until 12 weeks after therapy initiation but showed no significant change 2 months later. No correlation was found between baseline serum selenium levels and changes in exophthalmos, MRD1, TSAb, TSHR Ab, or CAS.Conclusions: Intravenous steroid therapy was effective in reducing TSAb, TSHR Ab, and CAS levels up to 2 months after therapy termination. However, it had limited positive impact on exophthalmos or eyelid retraction. Baseline selenium levels did not correlate with the changes in any of the examined parameters.

Vaccine-Induced Immunity Against Pertussis in Lung Transplant Candidates

Background. Given the high prevalence of Bordetella pertussis, patients with respiratory disorders are at risk of getting infected with this pathogen and developing pertussis. Therefore, they should be considered a target group for vaccination against this infection. Aims — the objective of the study was to assess vaccine-induced immunity against pertussis in lung transplant candidates. Methods. Twenty-four patients with severe bronchopulmonary diseases, aged 18 to 60, were vaccinated against pertussis with Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine. Five patients underwent lung transplantation. Immunoglobulin G (IgG) antibodies (Abs) were measured using the RIDASCREEN® Bordetella IgG test system. Results. In the post-vaccination period, only 8.3% of the patients developed such local reactions as tenderness and induration at the injection site. The proportions of patients who were seropositive for pertussis before vaccination, one month and one year after vaccination were 71, 100 and 100%, respectively (p = 0.02). A significant increase in anti-pertussis IgG Ab levels was identified one month after a single vaccine dose, and was still observed after 12 months. In the group of two-dose vaccination, there was no statistical difference between the levels of IgG Abs one month after the first dose and one month after the second dose. A significant increase in anti-Bordetella pertussis IgG Ab levels was observed in the group of initially seronegative patients compared to seropositive patients (p = 0.03). A year after vaccination, there was no statistically significant difference in IgG Ab levels between the patients with and without a history of lung transplantation. Conclusions. The majority (71%) of patients with severe bronchopulmonary disease was seropositive for B. pertussis. Single-dose vaccination against pertussis was safe; it induced the production of additional specific Abs and an increase in their levels in all patients. Therapy administered after lung transplantation did not significantly affect the levels of vaccine-induced Abs.

Appropriate Sampling and Longer Follow-Up Are Required to Rigorously Evaluate Longevity of Humoral Memory After Vaccination.

One of the goals of vaccination is to induce long-lived immunity against the infection and/or disease. Many studies have followed the generation of humoral immunity to SARS-CoV-2 after vaccination; however, such studies typically varied by the duration of the follow-up and the number of time points at which immune response measurements were done. How these parameters (the number of time points and the overall duration of the follow-up) impact estimates of immunity longevity remain largely unknown. Several studies, including one by Arunachalam etal. (2023. J. Clin. Invest. 133: e167955), evaluated the humoral immune response in individuals receiving either a third or fourth dose of mRNA COVID-19 vaccine; by measuring Ab levels at three time points (prior to vaccination and at 1 and 6 mo), Arunachalam etal. found similar half-life times for serum Abs in the two groups and thus suggested that additional boosting is unnecessary to prolong immunity to SARS-CoV-2. I demonstrate that measuring Ab levels at these three time points and only for 6 mo does not allow one to accurately evaluate the long-term half-life of vaccine-induced Abs. By using the data from a cohort of blood donors followed for several years, I show that after revaccination with vaccinia virus, vaccinia virus-specific Abs decay biphasically, and even the late decay rate exceeds the true slow loss rate of humoral memory observed years prior to the boosting. Mathematical models of Ab response kinetics, parameterized using preliminary data, should be used for power analysis to determine the most appropriate timing and duration of sampling to rigorously determine the duration of humoral immunity after vaccination.

The Frequency of Celiac Disease and Its Association with Infertility in Women Attending Infertility Clinics: A Case-Control Study in Southern Iran

Background: Celiac disease (CD) is a multifactorial systemic disease that causes enteropathy and can lead to a wide spectrum of disorders related to infertility. Objectives: This case-control study aimed to evaluate the frequency of celiac disease (CD) and its association with infertility in women. Methods: This study was conducted on women referred to Ghadir Mother and Child Hospital in Shiraz. Women with infertility served as the case group, while fertile women comprised the control group. Blood samples were collected from participants, and tissue anti-transglutaminase (Anti-TTG Ab) levels were measured. Patients with elevated Anti-TTG Ab levels were referred for duodenal biopsy. Results: One hundred subjects were enrolled in the case group and 200 in the control group. Eight patients in the case group tested positive for serology, and four of these had duodenal biopsies confirming CD. In the control group, one individual tested positive for serology, but the duodenal biopsy was negative (P for between-group differences: 0.001 for serology and 0.012 for biopsy results). There was a significant association between high levels of Anti-TTG Ab and infertility (odds ratio = 17.30, 95 % CI: 2.13 - 140.39), which remained even after adjusting for age and body mass index (odds ratio = 9.92, 95 % CI: 1.17 - 84.21). Conclusions: The frequency of CD was higher among infertile women compared to fertile women. Increased levels of Anti-TTG Ab were independently associated with infertility.

Breakthrough Infections in SARS-CoV-2-Vaccinated Multiple Myeloma Patients Improve Cross-Protection against Omicron Variants.

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants of concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral and cellular vaccine responses in MM patients stratified according to disease stage/treatment into group (1) monoclonal gammopathy of undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) after SCT with IT, and (4) progressed MM, and in healthy subjects (prospective cohort study). In contrast to SARS-CoV-2 hu-1-specific Ab levels, Omicron-specific Abs and their cross-neutralisation capacity remained low even after three booster doses in a majority of MM patients. In particular, progressed MM patients receiving anti-CD38 mAb and those after SCT with IT were Ab low responders and showed delayed formation of spike-specific B memory cells. However, MM patients with hybrid immunity (i.e., vaccination and breakthrough infection) had improved cross-neutralisation capacity against VOCs, yet in the absence of severe COVID-19 disease. Our results indicate that MM patients require frequent variant-adapted booster vaccinations and/or changes to other vaccine formulations/platforms, which might have similar immunological effects as BTIs.