Antibody-negative Patients Research Articles

Molecular and clinical profiles of pediatric monogenic diabetes subtypes: comprehensive genetic analysis of 138 patients.

Single gene variants that give rise to neonatal diabetes mellitus (NDM), maturity onset diabetes of the young (MODY) and syndromic forms of diabetes mellitus (SDM) are responsible for 3.1-4.2% of all diabetes cases. This single-center study with a relatively larger sample size aimed to evaluate the clinical and genetic characteristics of Chinese children with suspected monogenic diabetes (MD) using next generation sequencing (NGS) methods. Data were collected from 1550 consecutive children diagnosed with diabetes/hyperglycemia at the Endocrinology Department of Children's Hospital of Nanjing Medical University from 2012 to 2023. The genotype and phenotype of 138 children with suspected MD were retrospectively analyzed. Among 138 children, 16, 97, and 25 patients with NDM, suspected MODY and SDM were assessed by NGS, with a pick-up rate of 87.5%, 57.8%, and 56%, respectively. In total, there was a high pick-up rate of MD, with 58% (80 of 138) among antibody-negative pediatric patients. Pathogenic variants were found in GCK, HNF1A, INS, KCNJ11, INSR, HNF4A, ABCC8, WFS1, ALMS1, HNF1B, BLK and ZFP57 genes with 13 novel variants in addition to 4 patients with CNVs. In this cohort, GCK-MODY was the leading cause and the mildest type of MODY. GCK-MODY displayed favorable lipid profile when compared to non-GCK-MODY and MODYX, which might be cardioprotective. Following an accurate genetic diagnosis of diabetes, 19 patients switched from insulin therapy to oral agents or lifestyle interventions. NGS tests helped to identify the precise etiology of monogenic diabetic patients which has implications for better individualized management.

A study of autoimmune thyroid disease in pregnant women and its effect on fetal and maternal outcome

ABSTRACT Introduction: Anti-thyroid antibodies not only cause thyroid dysfunction but have independent adverse outcomes in the fetus and mother during pregnancy and after birth. Chronic lymphocytic thyroiditis as a presentation of immune system deregulation may be associated with a generalized activation of the immune system at the fetus–maternal unit, the placenta. This interference could be associated with pregnancy morbidities in m o t h e r a n d fetus. This study was done to find out the frequency of autoimmune thyroid disease and its effect on maternal and fetal outcomes in a tertiary care facility in Jharkhand. Method: This is an Observational Prospective Study done during an 18-month period on 254 pregnant women in their second trimester who came to the antenatal clinic (ANC) clinic with singleton pregnancy at RIMS Ranchi. Result: 222 (87.4%) out of the 254 pregnant women had anti- TPO antibodies less than 35 IU/ml. Anti-thyroid peroxidase (anti-TPO) antibody positivity with values greater than 35 IU/ml was found in 32 patients (12.6%). Anti-TPO antibody mean value was 22.54 ± 19.67 IU/ml. Among the 222 individuals who tested negative for the anti-TPO antibody, 7 (3.3%) had miscarriages, 182 (88.3%) gave birth vaginally, and 33 (14.9%) underwent a cesarean section. Of the 32 individuals who tested positive for the anti-TPO antibody, 2 (6.3%) had miscarriages, 24 (75.0%) had vaginal deliveries, and 6 (18.8%) had cesarean sections. Using the Chi-square test, a P value of 0.549 was calculated, indicating statistical insignificance (Pearson Chi-square test value = 0.200a). Conclusion: Anti-TPO antibody positivity was significantly related to miscarriage and anemia. Other complications like preterm delivery, pre-eclampsia, and low birth weight were higher in anti-TPO antibody-positive patients as compared to anti-TPO antibody-negative patients. However, these findings were not statistically significant.

The correlation of GluR3B antibody with T lymphocyte subsets and inflammatory factors and their role in the progression of epilepsy

ObjectiveTo investigate changes in proportions of peripheral blood lymphocyte subsets, the correlation between the lymphocyte subsets and cytokine levels in patients with GluR3B antibody-positive epilepsy, analyze the role of GluR3B antibodies and cytokines in the progression of epilepsy. In addition, the immunotherapeutic effect in patients with GluR3B antibody-positive epilepsy will be evaluated.MethodsPatients with epilepsy hospitalized in the Department of Neurology of the affiliated Hospital of Xuzhou Medical University from December 2016 to May 2023 were recruited. GluR3B antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Lymphocyte subset proportions were determined using flow cytometry, and serum concentrations of 12 cytokines were measured using cytometric beads array. Differences in T lymphocyte subsets and inflammatory factors were analysed between GluR3B antibody positive and negative patients. Structural equation modeling (SEM) was used to analyse the role of GluR3B antibodies and inflammatory factors in drug-resistant epilepsy (DRE). Finally, the therapeutic effect of immunotherapy on epilepsy patients with GluR3B antibodies was assessed.ResultsIn this study, sixty-four cases of DRE, sixty-six cases of drug-naïve epilepsy (DNE), and forty-one cases of drug-responsive epilepsy were recruited. (1) DRE patients with positive GluR3B antibody were characterized by a significant increase in the proportion of cluster of differentiation (CD)4+ T lymphocytes, a decrease in CD8+ T lymphocytes, and an increase of CD4+/CD8+ ratio. Similar alterations in T lymphocyte subsets were observed in GluR3B antibody-positive patients with DNE. GluR3B antibody levels correlated positively with CD4+ T lymphocytes (r = 0.23) and negatively with CD8+ T lymphocytes (r=-0.18). (2) In patients with DRE, the serum concentrations of interleukin-1β (IL-1β), IL-8, and interferon-gamma (IFN-γ) were significantly higher in those with positive GluR3B antibody compared to those with negative GluR3B antibody. Serum IL-1β levels were also higher in GluR3B antibody-positive DNE patients compared to antibody-negative DNE patients. In drug-responsive epilepsy patients with GluR3B antibody-positive, both serum IL-1β and IFN-γ levels were higher than those with GluR3B antibody-negative. Moreover, the concentrations of serum GluR3B antibody were positively correlated with the levels of IL-1β, IL-8, and IFN-γ. (3) SEM analysis indicated that GluR3B antibody may be a direct risk factor for DRE (direct effect = 4.479, 95%CI 0.409–8.503), or may be involved in DRE progression through affecting IFN-γ and IL-8 levels (total indirect effect = 5.101, 95%CI 1.756–8.818). (4) Immunotherapy significantly decreased seizure frequency and serum GluR3B antibody levels, and the seizure frequency was positively correlated with the levels of GluR3B antibody levels in patients receiving immunotherapy.ConclusionsThis study demonstrates that GluR3B antibody may influence the progression of epilepsy through altering the proportion of CD4+ and CD8+ lymphocyte subsets and increasing proinflammatory cytokines. The seizure suppression of immunotherapy is associated with the decrease of GluR3B antibody levels. Thus, the present study contributes to a better understanding of the immunoregulatory mechanisms of autoimmune-associated epilepsy and provides a potential target for DRE.

Interleukin-17 Gene Polymorphisms and Hepatitis B Virus Infection in a Sample of Iraqi Patients

Hepatitis B, a chronic inflammatory liver condition, constitutes a significant global health issue, with 3 million new cases and over 1 million deaths annually (when combined with hepatitis C). The infection may be acute or chronic, and it transmits horizontally by contact with biological fluids such saliva, blood, semen, tears, vaginal secretions, or perinatal fluids following childbirth, which are transferred from mother to infant. Infections can be easily prevented with immunization, typically administered shortly after birth; nevertheless, if neglected, chronic hepatitis B may lead to severe outcomes, including liver cancer or cirrhosis. Interleukin-17A, a pro-inflammatory cytokine, is essential in the immune response to many infections and is implicated in autoimmune diseases. The cytokine interleukin-17 (IL-17A) is only secreted by activated T cells. cDNA of IL-17 has been isolated and cloned from murine hybridomas (cytotoxic T lymphocyte antigen 8 (CTLA-8)). Cytokine imbalance is a crucial factor in the progression and growth of the hepatitis B virus (HBV). A cross-sectional study was conducted including 180 patients with HBV infection at the Digestive and Liver Diseases Teaching Hospital in Baghdad province, from December 14, 2022, to February 15, 2023. This study comprised two groups: the first group consisted of 40 HBV antibody-positive patients, while the second group included 40 HBV antibody-negative patients, along with a control group of 20 individuals. A blood sample of 5 ml was collected from each patient, divided into 2 ml in an anticoagulated EDTA tube and 3 ml in a gel tube. Whole blood with anticoagulated samples was utilized under optimal conditions for DNA extraction, while serum was isolated from blood for biochemical tests. The study comprised 180 patients, categorized into three groups: HBV Positive, HBV Cleared, and Control. The HBV Positive cohort consists of 99 individuals, comprising 54 males (54.45%) and 45 females (45.45%). The average age in this cohort is 42.52 years, accompanied by a standard deviation of 15.13 years. Of these individuals, 84 (84.85%) are wed. The HBV Cleared group has 45 individuals, including 24 males (53.34%) and 21 females (46.67%). The average age in this cohort is 48.43 years, with a standard deviation of 13.98 years. A predominant 39 persons (86.67%) are wed. The Control group comprises 36 individuals, primarily male, consisting of 24 men (66.67%) and 12 females (33.34%). Genotype distribution for two genetic markers, rs2275913 and rs10484879, among three groups: HBV Positive, HBV Negative, and Control. In the HBV Positive group for the rs2275913 marker, the AA genotype is present in 30 patients, the AG genotype in 36 patients, and the GG genotype in 36 patients. In the HBV Negative group, the AA genotype is observed in 9 patients, the AG genotype in 12 patients, and the GG genotype in 21 patients. Multiple research investigations have concentrated on the role of SNPs in the IL17A gene, particularly rs2275913 and rs10484879, in the susceptibility to chronic HBV infection. The polymorphisms were specifically examined for their possible impact on immune response and disease progression in patients infected with HBV. A study of the Han Chinese population demonstrated a significant correlation between the GG genotype and G allele of rs2275913 and an increased risk of HBV infection, suggesting a causal relationship with heightened susceptibility to viral infection.

The alternative value of thyroid stimulating hormone instead of thyroglobulin in differentiation of follicular thyroid neoplasm in Hashimoto's thyroiditis.

To provide novel aspects for the preoperative diagnosis and appropriate differentiation strategies for follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). Among 25,765 cases, a total of 326 patients with follicular thyroid neoplasms between 2013 and 2019 were enrolled. Patient demographics, perioperative parameters, surgical profiles and oncologic outcomes were collected and analyzed. There were no significant differences in preoperative ultrasound findings between FTA and FTC patients. The true positive rate (sensitivity) and true negative rate (specificity) of fine needle aspiration (FNA) for FTA patients were 0.6956 and 0.5000, respectively, and those for FTC patients were 0.0714 and 0.9348, respectively. Patients with FTC presented significantly higher serum thyroglobulin (TG) levels than patients with FTA. Preoperative TG level was positively related to tumor invasiveness and recurrence or distant metastases in FTC patients. There were 55 patients with Hashimoto's thyroiditis (HT), accounting for 16.87% of enrolled patients. HT patients had significantly lower serum TG concentrations than antibody-negative patients. Among HT patients, no significant differences were observed in TG levels between the FTA and FTC groups. Instead, FTA patients had significantly higher serum thyroid stimulating hormone (TSH) levels and lower serum T3 (Triiodothyronine) levels compared to FTC patients. Serum TSH level >1.736U/L was associated with benign follicular neoplasms in HT patients according to the receiver operating characteristic (ROC) curve. Distinguishing FTC from FTA remains a challenge for ultrasonography and FNA. Serum TG should be measured as a risk factor of FTC. However, in HT patients, serum TSH levels can serve as a more reliable indicator for differentiating FTC from FTA preoperatively.

Hepatitis C Virus Seroprevalence and Genotypic Distribution Among Hemodialysis Patients at a Teaching and Training Hospital in Western Rajasthan, India.

Background Hepatitis C virus (HCV) infection is a chronic hepatotropic blood-borne infection. The transmission of HCV in patients undergoing hemodialysis (HD) is more common in comparison to the general population due to factors such as frequent blood transfusions, prolonged vascular access, and the potential for nosocomial infections. Western Rajasthan in India is home to numerous teaching and training hospitals that cater to a large number of HD patients. Understanding the seroprevalence and genotypic distribution of HCV in this specific patient population is crucial for assessing the extent of infection within this vulnerable group for targeted surveillance and developing effectively tailored treatment protocolsin healthcare settings. Hence, this study was conducted with an aim to determine seroprevalence, seroconversion, and genotypes of HCV in HD patients at a tertiary care hospital. Methods This was a cross-sectional observational study. The duration of the study was from July 2019 to March 2022. In this study, the patients undergoing maintenance HD due to chronic kidney disease (CKD) were recruited. The data collected include patients' demographics, etiology of CKD, underlying other co-morbidities, duration of dialysis, and biochemical and blood count parameters. The patients recruited at the start of the study were screened for anti-HCV antibodies by HCV enzyme-linked immune sorbent assay (ELISA). The anti-HCV antibody-negative patients were followed up for the detection of anti-HCV antibodies. At the end of the follow-up period, all anti-HCV antibody negative samples in the pool of five and all anti-HCV antibody positive samples were subjected to a real-time polymerase chain reaction (RT-PCR) of 5' untranslated region (5'UTR) and core region, followed by line probe assay (LiPA). Results In this study, after applying inclusion and exclusion criteria, a total of 109 patients were recruited, out of which 64 (58.7%) were males and 45 (41.3%) were females. The age range of participants was 11-88 years with a mean and standard deviation of 46.75 and 16.35 years, respectively. A total of 39 patients (20 on screening, 19 on follow-up) were detected anti- HCV antibody positive. By RT-PCR, 24 patients tested HCV RNA positive (10 on screening, 14 on follow-up). Among 24 HCV RNA-positive samples, LiPA showed, HCV genotype 1a (n=21), genotype 3b (n=1), and two samples were detected to be inconclusive. Conclusion The increasing duration of dialysis is significantly associated with acquiring HCV infection. The majority of the cases of CKD in this geographical region are due to hypertensive nephropathy. There can be discordance between antibody and viral RNA positivity in HCV infection. The predominant HCV genotype identifiedin the dialysis ward of tertiary care hospital was genotype 1a.

Impaired survival of patients with non donor-specific anti-HLA antibodies before HLA-mismatched allogeneic stem cell transplantation

BackgroundWhile the detrimental role of donor-specific anti-HLA antibodies (DSAs) is well-described in the setting of hematopoietic stem cell transplantation (HSCT), few studies focus on non donor-specific ones and with controversial results. MethodsWe here report our monocenter experience on 64 adult patients receiving allogeneic HSCT from a HLA-mismatched donor between 2014 and 2022 who were tested for the presence of anti-HLA antibodies before transplant, focusing on fifteen patients with non donor-specific anti-HLA antibodies. ResultsThe survival of patients with non donor-specific anti-HLA antibodies was inferior with respect to patients without anti-HLA antibodies and similar to patients with DSAs. Median survival of patients with non donor-specific anti-HLA antibodies was 21 months (95 % CI: 9–42) vs. 61 months (95 % CI: 17–77) among the anti-HLA antibody-negative patients, with a significantly higher mortality incidence rate ratio (3.3 times-fold greater, p = 0.01). No pattern of death causes was found ConclusionsIn this monocenter series of HLA-mismatched HSCTs, impaired survival was observed in adult patients having non donor-specific anti-HLA antibodies before transplant, similar to those with DSAs. Our findings support those antibodies as a negative predictive factor even if they are not directed against the donor, thus warranting further investigation on larger cohorts.

Characteristics of after-discharges following compound muscle action potential or F-wave in primary peripheral nerve hyperexcitability syndrome.

F-wave testing frequently reveals after-discharges of varied morphologies in patients with primary peripheral nerve hyperexcitability syndrome (PNHS), although reports are scant. This study aimed to explore the morphological characteristics of the after-discharges during F-wave tests in PNHS, and to assess the association between after-discharges and the disease classification. We conducted a retrospective analysis of patients diagnosed with PNHS between 2014 and 2022. The morphological characteristic and duration of after-discharges during F-wave tests were analyzed. After-discharges in the Morvan syndrome group were compared with those in non-Morvan group, and between groups with positive or negative voltage-gated potassium channel (VGKC) complex antibodies. Twenty-nine patients were included in the study, of which 25 exhibited after-discharges. All after-discharges in Morvan patients occurred following compound muscle action potential (CMAP). In non-Morvan patients, after-discharges occurred following F-wave (32%) and CMAP (47%). The durations of after-discharges following CMAP were significantly prolonged in Morvan (54.2 ± 18.8 ms) compared to non-Morvan patients (34.5 ± 15.0 ms). The majority of antibody-positive patients (18/20) exhibited after-discharges following CMAP, whereas 67% of antibody-negative patients (6/9) showed after-discharges following F-wave. The varying presentations of after-discharges, including their location (after CMAP or F-wave) and the duration of after-discharge can assist in clinically classifying PNHS.

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units, and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody-negative patients. We observed statistical differences between antibody-positive and -negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody-positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

Brain-targeting autoantibodies in patients with dementia.

Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer's disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies.

#369 Anti-nephrin antibodies identify patients with steroid-resistant nephrotic syndrome responsive to immunosuppressants

Abstract Background and Aims The presence of circulating anti-nephrin antibodies has been recently reported in some patients with nephrotic syndrome (NS) and minimal change lesions, implying an autoimmune podocytopathy subset. We hypothesized that the presence of anti-nephrin antibodies would identify a subset of patients with steroid resistant NS (SRNS) and explain their response to second-line immunosuppressant therapy before and after kidney transplantation. Method We evaluated 31 patients with available kidney biopsy samples of our previously described prospective cohort of SRNS patients, genetically tested with whole exome sequencing at Meyer University Hospital IRCCS. By using high-resolution confocal microscopy, we assessed the co-localization between IgG and nephrin staining on kidney biopsy. To unequivocally establish anti-nephrin specificity of the deposited IgG, we performed super-resolution STimulated Emission Depletion (STED) microscopy. Results We observed anti-nephrin antibodies in 35.5% of patients with SRNS irrespective of podocytopathy lesion pattern. Antibody-positive (Antibody+) patients had a more severe NS at onset and better response to immunosuppression therapy compared to antibody-negative (Antibody-) patients. Only 1/11 Antibody+ patient developed chronic kidney disease compared to 9/20 Antibody- patients over a 10-year period. The single multidrug-resistant Antibody+ patient reached kidney failure had a pathogenic variant in the autosomal dominant-transmitted LMX1B. The patient experienced recurrence of NS after kidney transplantation with a positive response to plasmapheresis and rituximab. The allograft biopsy confirmed the presence of anti-nephrin antibodies. Conclusion The observed variability in patients with SRNS, influenced by a combination of genetic factors and nephrin autoimmunity, likely contributes to the diverse long-term outcomes and variations in responses to second-line immunosuppressant therapy.

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody negative patients. We observed statistical differences between antibody positive and negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

Comparison of Interstitial Lung Disease Between Antineutrophil Cytoplasmic Antibodies Positive and Negative Patients: A Retrospective Cohort Study.

Positive antineutrophil cytoplasmic antibodies (ANCAs) may occur in the setting of interstitial lung disease (ILD), with or without ANCA-associated vasculitis (AAV). We aim to compare the characteristics and clinical course of patients with ILD and positive ANCA (ANCA-ILD) to those with negative ANCA. We performed a single-center retrospective cohort study from 2018 to 2021. All patients with ILD and ANCA testing were included. Patient characteristics (symptoms, dyspnea scale, and systemic AAV), test results (pulmonary high-resolution computed tomography and pulmonary function tests), and adverse events were collected from electronic medical records. Descriptive statistics and the Fisher exact test were used to compare the outcomes of patients with ANCA-ILD to those with ILD and negative ANCA. A total of 265 patients with ILD were included. The mean follow-up duration was 69.3 months, 26 patients (9.8%) were ANCA positive, and 69.2% of those with ANCA-ILD had another autoantibody. AAV occurred in 17 patients (65.4%) with ANCA-ILD. In 29.4% of patients, AAV developed following ILD diagnosis. Usual interstitial pneumonia was the most common radiologic pattern in patients with ANCA-ILD. There was no association between ANCA status and the evolution of dyspnea,diffusing capacity of the lungs for carbon monoxide, and lung imaging. Forced vital capacity improved over time in 42% of patients with ANCA-ILD and in 17% of patients with negative ANCA (P = 0.006). Hospitalization occurred in 46.2% of patients with ANCA-ILD and in 21.8% of patients with negative ANCA (P = 0.006). Both groups had similar mortality rates. Routine ANCA testing should be considered in patients with ILD. Patients with ANCA-ILD are at risk for AAV. More research is required to better understand and manage patients with ANCA-ILD.

The first involved joints and associated factors in patients with rheumatoid arthritis.

This study aimed to investigate the first involved joints and associated factors in Turkish patients with rheumatoid arthritis (RA). This retrospective cross-sectional study included 300 newly diagnosed and disease-modifying antirheumatic drug-naïve RA patients (240 females, 60 males; mean age: 54±1.2 years; range, 18 to 82 years). Baseline demographic, clinical, and laboratory data were evaluated between January 2022 and December 2022. The patients were divided into four groups according to autoantibody profile: antibody-negative patients (Group 1; both RF and anti-CCP were negative in this group of patients), RF-positive patients (Group 2), anti-CCP-positive patients (Group 3), and patients with dual seropositivity with RF and antiCCP (Group 4). The patients were also divided into two groups according to the size of the first affected joint: patients with SJI at diagnosis and patients without SJI involvement at diagnosis. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody positivity rates were 40.3% and 35.6%, respectively. The mean lag time to diagnosis was 25±36 months. At the disease onset, 20% of patients did not have small joint involvement (SJI). Seronegative patients tended to be female (p=0.001), had longer lag time (p=0.001), and had lower levels of C-reactive protein (p=0.025), white blood count (p=0.005), and neutrophil/lymphocyte ratio (p=0.001) compared to the dual seropositive group. Patients presenting with SJI had a younger age (p=0.002), tended to be female (p=0.001), and had lower RF (p=0.034) and anti-CCP (p=0.031) positivity. Only age (p=0.005) and dual seronegativity (RF and anti-CCP; p=0.035) were the independent predictors of SJI in multivariate analysis. The decreasing age and seronegative status were defined as independent risk factors of SJI at the onset of RA. Population-based, prospective studies are needed for earlier diagnosis.

Clinical characteristics of patients with autoimmune nodopathy with anti-neurofascin155 antibodies.

According to the latest guidelines on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), patients with CIDP with anti-neurofascin 155 (NF155) antibodies are referred to as autoimmune nodopathy (AN), an autoimmune disorder distinct from CIDP. We aimed to compare the clinical data of patients with AN with anti-NF155 antibodies with those of anti-NF155 antibodies-negative patients with CIDP, and to summarize the clinical characteristics of patients with AN with anti-NF155 antibodies. Nine patients with AN with anti-NF155 antibodies and 28 serologically negative patients with CIDP were included in this study. Diagnosis was made according to the diagnostic criteria in the European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines on CIDP published in 2021. Demographics, clinical manifestations, electrophysiological examination, cerebrospinal fluid (CSF) tests, and response to treatment were retrospectively analyzed. Compared with serologically negative patients with CIDP, those patients with AN with anti-NF155 antibodies were younger (p=0.007), had a younger onset age (p=0.009), more frequent ataxia (p=0.019), higher CSF protein levels (p=0.001), and more frequent axon damage in electrophysiology (p=0.025). The main characteristics of patients with AN with anti-NF155 antibodies include younger age and onset age, limb weakness, sensory disturbance, ataxia, multiple motor-sensory peripheral neuropathies with demyelination and axonal damage on electrophysiological examination, markedly elevated CSF protein levels, and varying degrees of response to immunotherapy. Patients with AN with anti-NF155 antibodies differed from serologically negative patients with CIDP in terms of clinical characteristics. When AN is suspected, testing for antibodies associated with the nodes of Ranvier is essential for early diagnosis and to guide treatment.

Lymphocyte Crossmatch Testing or Donor HLA-DP and -DQ Allele Typing Effectiveness in Single Cord Blood Transplantation for Patients With Anti-HLA Antibodies Other Than Against HLA-A, -B, -C, and -DRB1

Anti-human leukocyte antigen (HLA) antibodies other than those against HLA-A, -B, -C, and DRB1 are a risk factor for engraftment delay and failure, especially in cord blood transplantation (CBT). The primary objective of this study was to assess the impact of the presence of anti-HLA antibodies on CBT and to evaluate the utility of lymphocyte crossmatch testing or additional HLA-DP and -DQ typing of CB units in improving transplant outcomes. We retrospectively assessed the engraftment rates and transplant outcomes of 772 patients who underwent their first CBT at our hospital between 2012 and 2021. Donors were routinely typed for HLA-A, -B, -C, and-DRB1 alleles, and the anti-HLA antibodies of recipients were screened before donor selection in all cases. Among patients who had antibodies against other than HLA-A, -B, -C, and DRB1 (n = 58), lymphocyte crossmatch testing (n = 32) or additional HLA-DP/-DQ alleles typing of CB (n = 15) was performed to avoid the use of units with corresponding alleles. The median patient age was 57 years (16 to 77). Overall, 75.7% had a high-risk disease status at transplantation, 83.5% received myeloablative conditioning regimens, and >80% were heavily transfused. Two hundred twenty-nine of the 772 recipients (29.6%) were positive for anti-HLA antibodies. There were no statistical differences in the number of infused CD34-positive cells between the anti-HLA antibody-positive and the anti-HLA antibody-negative patients. Of the 229 patients with anti-HLA antibodies, 168 (73.3%) had antibodies against HLA-A, -B, -C, and-DRB1 (Group A), whereas 58 (25.3%) had antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5 with or without antibodies against HLA-A, -B, -C, and -DRB1 (Group B). No patients in both Groups A and B exhibited donor-specific anti-HLA antibodies against HLA-A, -B, -C, and -DRB1. The neutrophil engraftment rate was lower in patients with anti-HLA antibodies than in those without antibodies (89.9% versus 94.1%), whereas nonrelapse mortality (NRM) before engraftment was higher in antibody-positive patients (9.6% versus 4.9%). In patients who received 2 or more HLA allele-mismatched CB in the host-versus-graft (HVG) direction (n = 685), the neutrophil engraftment rate was lower in the anti-HLA antibody-positive recipients than in the antibody-negative recipients with significant differences (88.8% versus 93.8%) (P = .049). Similarly, transplant outcomes were worse in the antibody-positive patients with respect to 2-year overall survival (OS) (43.1% versus 52.3%) and NRM (44.0% versus 30.7%) than in the antibody-negative patients. In contrast, the results of Group B were comparable to those of the antibody-negative patients, while those of Group A were statistically worse than the antibody-negative patients in terms of all engraftment rate (88.6%), OS (34.2%), and NRM (49.0%). The presence of anti-HLA antibodies negatively impacts engraftment, NRM, and OS in CBT. However, HLA-DP/-DQ allele typing of CB units or lymphocyte crossmatch testing could be a useful strategy to overcome poor engraftment rates and transplant outcomes, especially in patients with anti-HLA antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5.

Identification of potential biomarkers for neuromyelitis optica by quantitative proteomics.

Neuromyelitis optica (NMO) was a serious autoimmune inflammatory condition affecting the central nervous system. Currently, there was a lack of diagnostic biomarkers for AQP4-IgG-negative NMO patients. A comparative proteomic analysis was conducted on the CSF of 10 patients with NMO and 10 patients with non-inflammatory neurological disorders (NND) using tandem mass tagging technology. Differentially expressed proteins (DEPs) were analyzed using bioinformatic methods. The candidate proteins were then validated through ELISAs in a subsequent cohort of 160 samples, consisting of paired CSF and plasma samples from 50 NMO patients, CSF samples from 30 NND patients, and plasma samples from 30 healthy individuals. We identified 389 proteins via proteomics, screening 79 DEPs. NCAM1, SST and AHSG were selected as candidate molecules for further validation. Compared to NND patients, there were decreased levels of AHSG in CSF and increased levels of NCAM1 and SST in NMO patients. The ELISA results revealed significantly higher levels of AHSG, SST and NCAM1 in the CSF of the NMO group compared to the NND group. Similarly, the serum levels of these three proteins were also higher in the NMO group compared to the healthy control group. It was found that serum NCAM1 levels significantly decreased in patients with non-relapsed NMO compared to patients with relapsed NMO and CSF NCAM1 level increased in patients with bilateral NMO compared to patients with unilateral NMO. Furthermore, CSF SST levels increased in AQP4 antibody-positive NMO patients compared to AQP4 antibody-negative patients. CSF NCAM1, serum NCAM1 and serum SST may serve as potential biomarkers for NMO patients and aid in the diagnosis of AQP4 antibody-negative NMO patients.

Performance of assessment tools in predicting neural autoantibody positivity in patients with seizures

BackgroundThe identification of patients with seizures of unknown etiology who would benefit from neural antibody testing necessitates effective assessment tools.The study aimed to compare the performance of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and the “Obvious” Indications for Neural Antibody Testing in Epilepsy or Seizures (ONES) checklist. We also intended to evaluate whether the performance of the tools varied by types of antibody. MethodsPatients diagnosed with epilepsy, seizures, or status epilepticus of unknown etiology at West China Hospital from January 2019 to December 2021 were included. Paired serum/cerebrospinal fluid samples were analyzed for antineuronal and antiglial antibodies. The APE2 score and ONES checklist were applied, and their outcomes were compared to laboratory antibody test results. Possible false positive neuronal antibody results were excluded in sensitivity/specificity analysis reasonably. ResultsA total of 113 antibody-positive and 159 antibody-negative patients were enrolled in sensitivity/specificity analysis. The ONES checklist showed superior sensitivity than APE2 score (95.6 % vs.79.6 %, P < 0.001). Specificity was not statistically different (60.4 % vs. 57.9 %, P = 0.557). The negative predictive value (NPV) of ONES checklist was higher than that of APE2 score (94.8 % vs 80.7 %, P < 0.001). The positive predictive value of them was not statistically different (61.7 % vs 58.8 %, P = 0.557). APE2 score exhibited lower sensitivity for predicting LGI-Abs (52.9 % vs. 80.3 %, P = 0.022) compared to NMDAR-Abs. Similarly, ONES checklist showed lower sensitivity for LGI1-Abs than NMDAR-Abs (82.4 % vs. 100.0 %, P = 0.009). ConclusionsThe ONES checklist demonstrates superior sensitivity for neural antibody positivity than APE2 score. Specificity of the two assessment tools was similar. ONES checklist performed better NPV than the APE2 score. Both assessment tools performed less well in predicting the presence of LGI1- Abs when compared to NMDAR-Abs.

Role of FDG PET/CT in definitive and presumed autoimmune encephalitis.

F-18 Fluorodeoxyglucose PET/CT (FDG-PET) is emerging as a useful imaging adjunct to MRI in the initial diagnostic evaluation of autoimmune encephalitis (AIE)-though presently it is not included in the diagnostic criteria. In this prospective study we enrolled a total of 52 patients with clinically diagnosed and treated AIE. MRI evaluation was done in each case along with CSF and EEG where feasible. FDG-PET was done for all and images were interpreted visually and using SPM. The mean age group of patients included was 38.5 ± 22.6 years with 31 females and 21 males. 23 antibody-positive cases underwent PET, the most common antibody detected was anti-NMDAR type followed by anti-LGI 1. Most common metabolic pattern in NMDARE was hypermetabolism in basal ganglia and hypometabolism in parieto-occipital cortices and ovarian teratoma was detected in two of these patients on whole-body PET. A metabolic pattern consistent with AIE was demonstrated in 22/29 (75.8%) antibody-negative patients with hypermetabolism in basal ganglia and mesial temporal cortices. The overall sensitivity of FDG PET was 86% (45/52). MRI abnormalities were detected in 22/52 (42%) cases, 10/23 antibody positive and 12/29 antibody negative cases. PET was positive in 23/30 (76%) MRI negative cases. Sensitivity of FDG PET for supporting a diagnosis of AIE was higher compared to MRI in both antibody-positive (definitive) and antibody-negative (presumed) AIE. Specific metabolic patterns can be demonstrated on FDG PET in AIE, prompting an early diagnosis so that timely treatment can be instituted.

Prior COVID-19 infection is associated with persistent and higher thrombus burden in acute coronary syndromes

Abstract Background/Introduction The COVID-19 pandemic challenged global healthcare systems by causing a multi-organ syndrome with a high mortality rate. COVID-19 infection is associated with a profound inflammatory response and hypercoagulability in the acute phase, however little is known on the persistence of endothelial dysfunction and hypercoagulability beyond this phase and its impact on acute coronary syndrome (ACS). Purpose The purpose of this study was to investigate the effects of COVID-19 infection on the presentation and outcomes of coronary artery disease in patients with ACS. Methods A single centre prospective observational study was conducted from 10th of June 2020 to 6th of May 2021. Patients aged 18 or over presenting with ACS were included. Participants were excluded if they had active COVID-19 infection or if they did not undergo coronary angiography on admission. Study participants were tested one presentation for SARS-CoV-2 nucleoprotein (N) antibody and SARS-CoV-2 spike protein receptor binding domain (RBD) antibody to determine whether the participants had prior COVID-19 infection, COVID-19 vaccination, or neither at the time of their presentation. Data was collected on their baseline demographics, angiographic findings, and treatments. Patients were followed up via telephone call and electronic case record review to assess outcomes at one year. The primary end-point was all-cause mortality. Pre-specified secondary endpoints were cerebral infarction, repeat myocardial infarction or unplanned revascularisation and death (MACE) at one year, coronary artery ectasia, presence of thrombus, and thrombectomy requirement. Results 280 patients were approached for the study. 5 refused participation, 8 were lost to follow-up, 2 did not undergo coronary angiography, and 98 had uninterpretable/insufficient blood samples for antibody analysis. The remaining study population had 167 patients (median age 64 [43-85], 69.5% male). 22 (13.1%) had prior infection, 76 (45.5%) were antibody negative and 69 (41.3%) had a post COVID-19 immunisation response. 31.7% had diabetes mellitus, and 49.7% were smokers. There was no difference in the primary endpoint between the groups. Patients with prior COVID-19 infection were more likely to have coronary ectasia/aneurysm compared to vaccinated and antibody negative patients (57.1% vs 27.5% and 30.3%, respectively p = 0.034). They were also more likely to have thrombosis (61.9% vs 33.3% and 52.6%, p = 0.019), and undergo thrombectomy (19.0% vs 4.3% and 3.9%, p=0.027). Conclusions and Relevance Our findings suggest that COVID-19 infection may lead to persistent endothelial dysfunction and hypercoagulability, portending increased severity of coronary artery ectasia and coronary thrombosis even after recovery from the initial infection.