Prevalence Of Autoantibodies Research Articles

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study

Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects. Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels. In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group. Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner. AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference.

Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia

Aims/hypothesisWe aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations.MethodsA study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (n = 236, ≤35 years) and control participants (n = 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and HLA-DRB1 alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants.ResultsPatients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16–25 and 26–35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes. HLA-DRB1*03:01 (p = 0.0014) and HLA-DRB1*04 (p = 0.0001) were positively associated with this form of diabetes, while HLA-DRB1*15 was protective (p < 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (p = 1.60 × 10−7). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans.Conclusions/interpretationThe majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.

Prevalence of autoantibodies against Ras-like GTPases, RalA, in patients with gastric cancer.

Ras-like GTPases, RalA and RalB, are members of the Ras superfamily of small GTPases. RalA expression has been shown to be associated with aggressive clinicopathological characteristics and progression in cancer. RalA protein has been shown to be involved in immune reactions in some patients with cancer; however, the clinicopathological significance of serum RalA antibody in patients with gastric cancer has not been investigated. Serum samples of 291 patients with gastric cancer and 73 healthy controls were analyzed for serum RalA antibody using enzyme-linked immunosorbent assay. A cut-off optical density value was fixed at 0.255 (mean of control + 2 standard deviations). The clinicopathological and prognostic significance of s-RalA-Abs was evaluated. The positivity rate for serum RalA antibody (s-RalA-Abs) was 15%. The presence of serum RalA antibody was higher in younger patients compared with elderly patients, however this tendency was not statistically significant. s-RalA-Abs was not associated with tumor stage. Since s-RalA-Abs was independent of CEA (carcinoembryonic antigen) and carbohydrate antigen 19-9 (CA19-9), the combination of s-RalA-Abs with CEA and CA19-9 significantly increased the detection rate of gastric cancer at each tumor stage. Patients who were tested positive for s-RalA-Abs showed poor long-term survival; however, this association was not statistically significant by multivariate analysis. In conclusion, s-RalA-Abs may be a candidate serum marker for gastric cancer, when used in combination with CEA and/or CA19-9. Additionally, the presence of s-RalA-Abs, in combination with CEA and/or CA19-9, was associated with poor survival in patients with gastric cancer.

The Effect of Proteinuria on Antinuclear Antibody Assay Results in Patients with Glomerulonephritis

Background:Glomerulonephritis mostly results from dysregulated immune system. Impaired immune mechanisms can be primary or secondary to an autoimmune disorder. Antinuclear antibodies (ANA) are hallmark of autoimmunity and are frequently present at high titer (≥ 1: 160). ANA are characterized via anti-double stranded deoxyribonucleic acid (dsDNA) and antiextractable nuclear antigen (ENA) antibodies for the identification of underlying autoimmune disease. Heavy proteinuria can affect assessment of autoantibodies hence special attention is required for the definitive diagnosis in such cases.Objective:Our aim was to determine impact of heavy proteinuria on ANA titer, anti-dsDNA and anti-ENA antibodies in glomerulonephritis patients.Methods:150 glomerulonephritis patients were enrolled in this study. All had antinuclear antibodies, samples were tested for anti-dsDNA and anti-ENA. ANA titer of ≥1:160 was taken significant. Proteinuria was assessed by spot protein/creatinine ratio. Data was analyzed using SPSS software version. 20Results:Heavy proteinuria was present in 119(79%) patients. Low ANA titer(≤1:80) was present in 37(25%) patients. Of 33 patients with heavy proteinuria and low ANA titer, ANA was characterized in 11 patients. These include anti-dsDNA(two), anti-SSA(four), anti-Sm (one), antihistones( one), anti-RNP(two), anti-Pm-Scl(one) and anti-ribosomal P protein (two).There was no significant difference in the prevalence of various autoantibodies in patients with high or low ANA titer with heavy proteinuria.Conclusion:This study highlights the importance of low ANA titer in glomerulonephritis patients in the setting of heavy proteinuria. Significant protein loss may alter actual titer of autoantibodies. Hence in this scenario clinically correlation along with ANA characterization via specific autoantibodies is required for adequate patient management.

Thyroid Autoantibodies in Egyptian Patients with Autoimmune Rheumatic Diseases: Relation to Disease Activity and Functional Impairment

Background: Autoantibodies against the thyroid seem to be more common in patients with rheumatic diseases than in the normal population. Their appearance may be linked to an associated autoimmune thyroid disease. Knowing the degree of association between rheumatic and thyroid diseases may help the clinician to make the correct decision. Objectives: The aim of the work was to estimate the prevalence of thyroid autoantibodies among patients with systemic autoimmune rheumatic diseases with or without thyroid disorders and its association with disease activity and functional impairment. Patients and Methods: The current study included 60 patients and 20 healthy controls. Patients were divided into three groups; systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc). Clinical and laboratory assessment were done to all patients including routine laboratory investigations and thyroid function tests (thyroid stimulating hormone [TSH], T3 and T4), and thyroid autoantibodies; anti- thyroglobulin (TgAb) and anti-thyroperoxidase (TPOAb). Results: SLE group had significant (P=0.018) lower age than other groups. Antithyroid antibodies and thyroid disorders were more common in SSc and SLE patients than RA patients and control subjects; however, no significant difference between studied groups. Presence of autoantibodies with and without thyroid disorders was not associated with the activity or functional indexes evaluated. Conclusion: The prevalence of thyroid autoantibodies in SLE and SSc patients was higher than in RA patients. No link could be established between the presence of thyroid autoantibodies and the results from any of the instruments used to measure inflammatory activity and functional impairment in these cases of rheumatic diseases.

Thyroid Autoantibodies in Egyptian Patients with Autoimmune Rheumatic Diseases: Relation to Disease Activity and Functional Impairment

Background: Autoantibodies against the thyroid seem to be more common in patients with rheumatic diseases than in the normal population. Their appearance may be linked to an associated autoimmune thyroid disease. Knowing the degree of association between rheumatic and thyroid diseases may help the clinician to make the correct decision. Objectives: The aim of the work was to estimate the prevalence of thyroid autoantibodies among patients with systemic autoimmune rheumatic diseases with or without thyroid disorders and its association with disease activity and functional impairment. Patients and Methods: The current study included 60 patients and 20 healthy controls. Patients were divided into three groups; systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc). Clinical and laboratory assessment were done to all patients including routine laboratory investigations and thyroid function tests (thyroid stimulating hormone [TSH], T3 and T4), and thyroid autoantibodies; anti- thyroglobulin (TgAb) and anti-thyroperoxidase (TPOAb). Results: SLE group had significant (P=0.018) lower age than other groups. Antithyroid antibodies and thyroid disorders were more common in SSc and SLE patients than RA patients and control subjects; however, no significant difference between studied groups. Presence of autoantibodies with and without thyroid disorders was not associated with the activity or functional indexes evaluated. Conclusion: The prevalence of thyroid autoantibodies in SLE and SSc patients was higher than in RA patients. No link could be established between the presence of thyroid autoantibodies and the results from any of the instruments used to measure inflammatory activity and functional impairment in these cases of rheumatic diseases.

Evaluation of autoantibodies and immunoglobulin G subclasses in women with suspected macroprolactinemia.

BackgroundMacroprolactin mostly composed of an immunoglobulin G (IgG) and a monomeric prolactin (PRL) represents the major circulating PRL form in the patients with macroprolactinemia that are usually asymptomatic and may not require treatment. In this study, we aimed to evaluate the prevalence of antithyroid and antinuclear antibodies, as well as the IgG subclass distributions in the patients suspected for macroprolactinemia.MethodsFrom January to July in 2018, totally 317 patients with elevated PRL were subjected to the polyethylene glycol (PEG) precipitation assay. The patients with recovery rates of ≤60% were subjected for IgG subclass determination and autoantibody testing including thyroid peroxidase antibody (aTPO), antithyroglobulin antibody (aTG), and antinuclear antibodies (ANA).ResultsThe higher the post‐PEG PRL recovery rates, the less typical hyperprolactinemia symptoms and the higher prevalence of autoantibodies were observed. The IgG1 and IgG3 were the predominant subclasses in the PRL‐IgG complexes according to the immunoprecipitation experiments.ConclusionThe patients with post‐PEG PRL recovery rates of <40% and 40%‐60% were likely to represent two distinct populations of different clinical presentations. The prevalence of autoantibodies and IgG subclasses distribution suggested their pathogenic significance in the development of macroprolactinemia.

Islet, thyroid and transglutaminase antibodies in adult Bulgarian patients with type 1 diabetes.

The aim of the study was to assess the prevalence and relationship of islet antibodies and autoantibodies of the most common associated autoimmune diseases-autoimmune thyroid disease (AITD) and celiac disease, in adult Bulgarian patients with type 1 diabetes of short duration. 160 type 1 diabetes patients, of mean age 36.3 ± 10.9 years, mean BMI 23.0 ± 4.2 kg/m2 and mean disease duration 1.35 ± 1.69 years were enrolled. Pancreatic islet cell antibodies-glutamic acid decarboxylase antibodies (GAD 65-Ab), tyrosine phosphatase antibodies (IA 2-Ab), and zinc transporter 8 antibodies (ZnT8-Ab), thyroid antibodies-thyroperoxidase and thyroglobulin antibodies, and transglutaminase antibodies (TTG-IgA-Ab) were assessed by ELISA. 87.5% of the patients had one or more of the islet antibodies-78.1% had GAD 65-Ab, 53.1%-ZnT8-Ab, and 34.4%-IA 2-Ab. 5% presented as just ZnT8-Ab positive. GAD 65-Ab identified 90.6% of the antibody positive patients. The addition of IA 2-Ab as a second immunologic marker identified 94.4%, while the use of ZnT8-Ab in second place identified 98.8% of the cases. 24.4% presented with positive thyroid antibodies and 33.8% had AITD. No relation was found between any of the islet antibodies and AITD. None of the patients was TTG-IgA-Ab positive. No significant correlations were established between the antibodies with different organ specificity. In adult Bulgarian type 1 diabetes patients ZnT8-Ab is an independent diagnostic marker rating second in prevalence and diagnostic significance after GAD 65-Ab. AITD affects about one third of this population and routine screening is required, while screening for celiac disease is not justified.

RETRACTED: Antibodies to cellular prion protein and its cognate ligand stress-inducible protein 1 in systemic lupus erythematosus.

ObjectivesThis study aimed to determine the prevalence of autoantibodies to cellular prion protein (PrP(C)) and its cognate ligand stress-inducible protein 1 (STI-1) in sera from patients with syst...

Chikungunya-Induced Arthritis in Reunion Island: A Long-Term Observational Follow-Up Study Showing Frequently Persistent Joint Symptoms, Some Cases of Persistent Chikungunya Immunoglobulin M Positivity, and No Anticyclic Citrullinated Peptide Seroconversion After 13 Years.

Reunion Island was struck by a massive Chikungunya outbreak in 2005-2006. Chikungunya infection is characterized by inflammatory joint symptoms, which may evolve into chronic arthritis. In this long-term longitudinal observational monocentric study, after the 2005-2006 outbreak in Reunion Island, 159 patients were first referred to a rheumatologist for post-Chikungunya chronic musculoskeletal pain, 73 of them were diagnosed with classifiable Chikungunya-related chronic inflammatory rheumatic diseases (>3 month symptom duration from the initial viral infection). Thirty of these 73 patients were clinically evaluated by a second rheumatologist in 2018-2019. The main objective of this second examination was to estimate the proportion of patients with persistent Chikungunya-related inflammatory joint symptoms after 13 years. Inflammatory joint symptoms persisted in 17/30 patients after 13 years (therefore in at least 23.3% of the 73 patients initially diagnosed with Chikungunya-related inflammatory joint symptoms and 10.7% of the 159 patients referred for post-Chikungunya chronic musculoskeletal pain). In the symptom persistence subgroup, the prevalence of positive autoantibodies (antinuclear or ACPA) was significantly higher - without any seroconversion, Chikungunya IgG and IgM levels were higher, long-term IgM positivity and radiographic damage were more frequent. Overall, after 13 years, pain and fatigue levels remained significant, 5 patients were still treated by methotrexate, 3 by TNF-blockers, highlighting long-term Chikungunya-related patient burden. Such a long-term persistence of Chikungunya-related chronic inflammatory rheumatic diseases had not been reported so far. Furthermore, the long-term Chikungunya IgM positivity we observed in some cases might corroborate the hypothesis of residual viral antigen-driven chronic arthritis.

M99. INVESTIGATING THE BEST PREDICTIVE CLINICAL FEATURES OF ANTI-N-METHYL-D-ASPARTATE RECEPTOR (NMDAR) ENCEPHALITIS IN THE 2010 AUSTRALIAN NATIONAL SURVEY OF HIGH IMPACT PSYCHOSIS (SHIP) COHORT

BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, a recently reported autoimmune disorder, can be mistakenly diagnosed as a psychotic disorder, especially schizophrenia, as patients can present with prominent psychotic symptoms, in particular persecutory ideation, hallucinations and disturbed speech. In this study we used machine learning of the clinical data in a large cohort of persons with a positive psychosis history to ascertain whether we could predict NMDAR-positive cases, and which variables most accurately distinguished between NMDAR-positive and -negative cases.MethodsSHIP collected nationally representative data from 1825 individuals with a psychotic illness. Plasma samples were available for n=472. To investigate the prevalence of NMDAR autoantibodies a recombinant indirect immunofluorescence test was performed (EuroImmun AG, Lübeck, Germany), with NMDAR transfected human embryonic kidney (HEK) 293 cells quantified using NIS Elements software. NMDAR-positive cases were estimated. Gradient boosting machine learning (the data were randomly split: 60% for initial ascertainment and 40% for validation) was subsequently performed using the clinical data available: 120 variables in total across various domains of sociodemographic, medical history, psychiatric diagnosis and current psychiatric symptoms. Only the variables found to have significant (or near significant) association with being NMDAR-positive were used to develop rules for identifying cases.ResultsThere were 38 NMDAR-positive cases. They were more likely to be associated with a schizophrenia /schizoaffective and a depressive psychosis diagnosis, and less likely to be associated with a bipolar diagnosis, than antibody-negative cases. They were also more likely to be associated with a single episode with good recovery, and with anxiety symptoms and dizziness in the prior 12 months (which included light headedness, feeling faint and unsteady). For the present state symptoms, restricted affect was more likely to be present whereas poverty of speech was rare. Initial insomnia and a medical history that included epilepsy were not present for any of the NMDAR-positive cases. The machine learning algorithm was able to successfully classify 94% of cases to the correct antibody group.DiscussionIn this significant Australian epidemiological cohort, we have identified key clinical features associated with anti-NMDAR encephalitis, including diagnosis, and symptoms and clinical course. The novel and insightful analyses afforded by using machine learning should be replicated in other samples to confirm the important clinical findings reported in the current work.

Clinical and functional consequences of anti-properdin autoantibodies in patients with lupus nephritis.

Properdin is the only positive regulator of the complement system. In this study, we characterize the prevalence, functional consequences and disease associations of autoantibodies against properdin in a cohort of patients with autoimmune disease systemic lupus erythematosus (SLE) suffering from lupus nephritis (LN). We detected autoantibodies against properdin in plasma of 22·5% of the LN patients (16 of 71) by enzyme-linked immunosorbent assay (ELISA). The binding of these autoantibodies to properdin was dose-dependent and was validated by surface plasmon resonance. Higher levels of anti-properdin were related to high levels of anti-dsDNA and anti-nuclear antibodies and low concentrations of C3 and C4 in patients, and also with histological signs of LN activity and chronicity. The high negative predictive value (NPV) of anti-properdin and anti-dsDNA combination suggested that patients who are negative for both anti-properdin and anti-dsDNA will not have severe nephritis. Immunoglobulin G from anti-properdin-positive patients' plasma increased the C3b deposition on late apoptotic cells by flow cytometry. Nevertheless, these IgGs did not modify substantially the binding of properdin to C3b, the C3 convertase C3bBb and the pro-convertase C3bB, evaluated by surface plasmon resonance. In conclusion, anti-properdin autoantibodies exist in LN patients. They have weak but relevant functional consequences, which could have pathological significance.

An Examination of Changes in Urinary Metabolites and Behaviors with the Use of Leucovorin Calcium in Children with Autism Spectrum Disorder (ASD)

Children with autism spectrum disorder (ASD) have been found to have a high prevalence of folate receptor auto-antibodies (FRAA), which may impair the normal transport of folate from blood into the cerebrospinal fluid (CSF). Leucovorin calcium (LC) is believed to bypass the folate transport system and restore function. We sought to examine changes in behavior and urinary metabolites in children and young adults with ASD being treated with LC. Students attending a K-12 school for ASD were recruited for an open-label, 12-week study of high-dose LC (2 mg/kg/day, max dose 50 mg/day). The primary outcome measures were the mean changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). We also examined changes in Pediatric Quality of Life (PedsQL) and urinary metabolites. Changes were assessed with paired sample t-tests. Twelve students aged 13 to 19 (2 girls, 10 boys) completed the study. The parent-reported SRS showed a non-significant decrease (improvement) of 7.8 points (95% CI − 1.6 to 17.3, p = 0.095), and the ABC showed a non-significant decrease of 2.4 points (95% CI − 6.4 to 11.3, p = 0.56). The teacher-reported ABC and the parent-reported PedsQL showed very little change. Urinary metabolites with the greatest changes were involved in folate, phosphatidylcholine, and tocopherol metabolism. In an open-label study of school-aged children with ASD, LC treatment did not lead to significant improvements. The parent-reported SRS showed a non-significant improvement of 7.8 points, which is clinically important and worthy of future study with larger samples. The potential benefits of LC may be limited to children with a specific physiological abnormality (e.g., FRAA status) and may require a targeted treatment approach. Urinary metabolites may be a useful tool to identify children who are likely to respond to treatment.

Anti-complement factor H autoantibodies may be protective in lupus nephritis

BackgroundThis study aimed to investigate the role of anti-CFH autoantibodies in lupus nephritis based on a well-defined cohort. MethodsOne hundred twenty patients with biopsy-proven active lupus nephritis were collected as the discovery cohort, sixty patients served as the validation cohort, thirty-four patients with SLE without renal involvement (NR-SLE) were as disease controls, and thirty healthy donors were also included. The anti-CFH autoantibodies and IgG subclasses were detected by ELISA, and epitopes were evaluated by western blot. Anti-CFH autoantibodies were purified by affinity chromatography column, and the interference on the biofunctions of CFH was further studied by the C3b binding assay and cofactor activity assay in vitro. ResultsThe prevalence of anti-CFH autoantibodies in lupus nephritis was significantly higher than that in healthy controls (8.3% (10/120) vs. 0% (0/30), P = 0.017), and no significant difference was found between the discovery and the validation group (8.3% (10/120) vs. 11.7% (7/60), P = 0.268) or the discovery and the NR-SLE group (8.3% (10/120) vs. 11.8% (4/34), P = 0.231). The subclass was mainly IgG2 (7/10), and major epitopes were in the middle (8/10 in SCRs 11–14) and N-terminal (7/10 in SCRs 1–4) regions of CFH. Patients with anti-CFH autoantibodies had a significantly lower prevalence of acute kidney injury (0% (0/10) vs. 40.0%(4/10), P = 0.025), lower serum creatinine levels (0.76 (0.40, 1.06) vs. 1.43 (0.46, 11.15), mg/dL, P = 0.023), and higher hemoglobin levels (113.8 ± 24.63 vs. 90.0 ± 22.53, g/L, P = 0.037) than those who were negative after further stratified analysis. A functional study showed that anti-CFH autoantibodies purified from patients with lupus nephritis could improve the binding between CFH and C3b, and also enhance the cofactor activity of CFH in vitro. ConclusionsAnti-CFH autoantibodies were detected in patients with lupus nephritis in approximately 10% of patients with polyepitopes and IgG2 subclass predominance. Patients with anti-CFH autoantibodies presented with milder renal damage, and the purified autoantibodies could enhance the C3b binding and CFI cofactor activity of CFH in vitro, which suggested a protective role in the lupus nephritis.

Autoantibody Prevalence in Cerebrospinal Fluid in Autoimmune Encephalitis and Related Disorders: The Need for a More Targeted Screening Approach

Abstract Detection of a neural autoantibody can confirm diagnosis and guide patient management and treatment. Recent recommendations suggest concurrent serum and cerebrospinal fluid (CSF) testing. However, most studies on prevalence of these autoantibodies have focused on serum testing. Herein we performed a retrospective review of CSF specimens submitted to Mayo Clinic Laboratories for CSF panel (Encephalopathy, Dementia, Paraneoplastic or Epilepsy) testing. Autoimmune encephalitis-associated and other autoimmune neurologic disorder-associated autoantibody prevalence was evaluated in conjunction with ordering patterns for CSF testing only or paired with serum testing to evaluate the clinical relevance of autoantibody testing in CSF. An overall positivity rate of 4.63% (112/2420) was observed, with 95.54% (107/112) CSF specimens positive for a single autoantibody. The CSF positivity rates were highest for antibodies associated with autoimmune encephalitis (GAD65&amp;gt;NMDA&amp;gt;GABA-B&amp;gt;LGI1&amp;gt;AMPA&amp;gt;VGKC) except CASPR2 which was not detected, while antibodies associated with paraneoplastic syndrome were less prevalent (ANNA-1/Hu&amp;gt;PCA-1/Yo&amp;gt;CRMP-5/CV2&amp;gt;AGNA-1/SOX-1&amp;gt;PCA-2) or not detected (amphiphysin, ANNA-2/Ri, ANNA-3 and PCA-Tr). Most CSF specimens (62.56%; n=1514) did not have a paired serum submitted for testing. Of 906 CSF/serum pairs, only 49 were CSF autoantibody positive. Rarely were antibodies identified in CSF with negative serum results while antibodies were more frequently identified in serum with negative CSF results. These data indicate that test utilization for neural autoantibodies in CSF could be substantially improved by basing ordering practices on clinical manifestations and autoantibody prevalence.

Prominent antibody mediated auto-immune response in idiopathic CD4 lymphopenic patients

Abstract Patients with Idiopathic CD4 Lymphocytopenia (ICL) have low circulating CD4 T cell numbers, accompanied sometimes by low numbers of CD8, B and/or NK cells, making them susceptible to opportunistic infections. The etiology is unknown and there is no familiar linkage. In spite of their immune deficiency 32% of ICL patients have clinically defined auto-immune disease. To analyze the presence of auto-antibodies in these patients we hybridized sera from 34 patients and 15 healthy control (HC) to a 9,000 proteins human array. When identifying positive targets as the ones with Z score ≥4 we found that all 34 ICL patients, unrelated to their autoimmune disease manifestations, had IgG antibodies against tens of proteins while the HC had none. There was considerable variability in both numbers and identities of targets. We next evaluated whether some of these antigens might be displayed on the T cell membrane. Using a flow-based assay we tested sera from 72 ICL patients and found that 50% of them had either IgG, mostly but not exclusively IgG1 and/or IgG4 isotypes, or IgM antibodies against T cell membrane proteins. Functionally, 50% of the plasma with IgG1 or IgG3 antibodies induced antibody dependent cell mediated cytotoxicity against healthy T-lymphocytes. In addition, sera from 20% of the patients with anti-lymphocyte antibodies induced complement deposition on healthy CD3 T cells and some of them induced complement dependent cytotoxicity. Furthermore, we observed complement deposition (C1q, C4c and C3b) on CD4 T cells in 14% of the 72 ICL patients when analyzed directly ex vivo. Our data support a high prevalence and pathogenicity of autoantibodies in ICL, which offers a potential therapeutic target.

Autoantibody Prevalence in Cerebrospinal Fluid in Autoimmune Encephalitis and Related Disorders: The Need for a More Targeted Screening Approach (4897)

Autoantibody Prevalence in Cerebrospinal Fluid in Autoimmune Encephalitis and Related Disorders: The Need for a More Targeted Screening Approach (4897)

Autoantibody profile in a cohort of Algerian patients with systemic sclerosis.

To describe the autoantibody profile in a cohort of Algerian patients with systemic sclerosis (SSc) and to determine clinical associations between SSc-related autoantibodies, disease subtypes and specific clinical features. Consecutive Algerian patients with SSc were included in the present study. In addition to clinical characterization, all subjects underwent autoantibody testing using indirect immunofluorescence, immunoenzymatic, and line immunoblot assays. A total of 150 patients were included in this study, 103 (68.7%) had limited cutaneous SSc (lcSSc), 42 (28%) had diffuse cutaneous SSc (dcSSc) and 5 (3.3%) had sine cutaneous scleroderma. One hundred thirty-five (90.0%) patients were positive for SSc-related autoantibodies, including 63 (42%) with more than one autoantibody. The two most frequent autoantibodies were anti-topoisomerase I (ATA) (76; 50.7%) and anti-SSA/Ro (49; 32.7%). Only 23 (15.3%) patients were positive for anticentromere; 9 (6%) were positive for anti RNA polymerase III; 5 (3.3%) for anti-U3 RNP; 3 (2%) for anti Th/To; 25 (16.7%) for anti-U1 RNP; 11 (7.3%) for anti-PM/Scl and 4 (2.7%) for anti-Ku. Anti-topoisomerase I was associated with dcSSc (p <0.0001), interstitial lung disease (ILD) (p <0.0001) and digital ulcers (p <0.0001). Anti-U3 RNP was associated with pulmonary arterial hypertension (PAH) (p=0.031). Notable similarities and differences in the prevalence of SSc-related autoantibodies were found in our population when compared to other ethnic groups. ATA and anti-U3 RNP may be a reliable biomarker for ILD and PAH. Further studies should be conducted to better understand the ethnic influence on disease expression and autoantibody production.

Analysis of myositis autoantibodies in Chinese patients with cancer-associated myositis.

BackgroundCancer‐associated myositis (CAM) has poor prognosis and causes higher mortality. In general, myositis‐specific autoantibodies (MSAs) and myositis‐associated autoantibodies (MAAs) have been shown to be useful biomarkers for its diagnosis.MethodsIn the present study, focus was given in assessing the presence, prevalence, and diagnostic values of myositis autoantibodies in Chinese patients diagnosed with CAM. The sera collected from 49 CAM patients, 108 dermatomyositis/polymyositis (DM/PM) patients without cancer, 105 disease controls, and 60 healthy controls were detected for the presence of 16 autoantigens (Jo‐1, OJ, EJ, PL‐7, PL‐12, MDA5, TIF1γ, Mi‐2α, Mi‐2β, SAE1, NXP2, SRP, Ku, PM‐Scl75, PM‐Scl100, and Ro‐52) using a commercial Euroline assay.ResultsThe frequency of anti‐TIF1γ was significantly higher in CAM patients than in DM/PM patients without cancer (46.9% vs 14.8%, P < .001). Importantly, the sensitivity and specificity for this MSA were 46.9% and 85.2%, respectively. These helped to differentiate CAM patients from DM/PM patients without cancer. However, there was no difference in other MSAs and MAAs between CAM and DM/PM patients without cancer.ConclusionThe present study indicates that anti‐TIF1γ levels can serve as important biomarkers for CAM diagnosis and help in distinguishing between CAM and DM/PM patients without cancer.

Prevalence of anti-DFS70 autoantibodies in a Latin American cohort of patients with systemic lupus erythematosus and without autoimmune diseases.

Anti-dense fine speckled 70 (DFS70) autoantibodies were reported to be more prevalent in healthy individuals than those with autoimmune diseases such as systemic lupus erythematosus (SLE). We determined anti-DFS70 autoantibody prevalence in a Latin American cohort of patients with SLE and healthy individuals. This study included 127 individuals with anti-nuclear antibodies (ANAs; > 1:160) suggesting the presence of anti-DFS70, including 64 patients with SLE and 63 healthy controls. The anti-DFS70 autoantibodies were determined by immunoadsorption using NOVA Lite® HEp-2 Select kit with DAPI. Negative fluorescence after adsorption with the DFS70 antigen indicated anti-DFS70 autoantibody positivity. The presence of anti-DFS70 autoantibodies was confirmed by indirect immunofluorescence in 21 (33.3%) healthy controls and 8 (12.5%) patients with SLE (p = 0.005). Among the anti-DFS70-positive patients with SLE, the most frequent compromise was renal involvement in six cases (75%), 4 patients (37.5%) were positive for anti-Sm, which was the most frequently associated antibody, and one patient (12.5%) was positive for anti-DNA. Anti-DFS70 autoantibodies might be considered a biomarker to differentiate patients with SLE from ANA-positive individuals without autoimmune diseases. • In a Latin American cohort, the anti-DFS70 was higher in individuals without autoimmune diseases compared with that in patients with SLE.• The anti-DFS70 might have utility as a biomarker of exclusion in patients with non-specific clinical signs of AARDs.