Autoantibody Testing Research Articles

Polymer scaffolds delineate healthy from diseased states at sites distal from the pancreas in two models of type 1 diabetes.

Type 1 diabetes (T1D) prevention is currently limited by the lack of diagnostic tools able to identify disease before autoimmune destruction of the pancreatic β cells. Autoantibody tests are used to predict risk and, in combination with glucose dysregulation indicative of β cell loss, to determine administration of immunotherapies. Our objective was to remotely identify immune changes associated with the disease, and we have employed a subcutaneously implanted microporous poly(e-caprolactone) (PCL) scaffold to function as an immunological niche (IN) in two models of T1D. Biopsy and analysis of the IN enables disease monitoring using transcriptomic changes at a distal site from autoimmune destruction of the pancreas, thereby gaining cellular level information about disease without the need for a biopsy of the native organ. Using this approach, we identified gene signatures that stratify healthy and diseased mice in both an adoptive transfer model and a spontaneous onset model of T1D. The gene signatures identified herein demonstrate the ability of the IN to identify immune activation associated with diabetes across models.

A case of Buerger's disease with vasculopathy and skin fibrosis requiring differential diagnosis from systemic sclerosis.

Buerger's disease is characterized by peripheral ischemia due to occlusion of small- and medium-sized arteries in the extremities. This report describes a case of Buerger's disease in a 51-year-old male who presented with findings resembling systemic sclerosis. The patient exhibited Raynaud's phenomenon in year X-3, which developed to skin hardening, nail avulsion, and ulceration of the right fingers in year X. Diagnostic testing showed positive microvasculopathy on nailfold videocapillaroscopy (NVC) and positive fibrosis on skin biopsy. Although the patient fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for systemic sclerosis, several findings in this case were atypical for systemic sclerosis, including left-right asymmetry in finger involvement, nail loss, and negative autoantibody tests. Contrast-enhanced computed tomography showed poor perfusion of the right ulnar artery, and a heavy smoking history was established in the patient case. Therefore, based on Shionoya's criteria, he was diagnosed with a case of Buerger's disease confined to the upper extremity. Smoking cessation and vasodilator therapy resulted in the prompt resolution of ischemic symptoms, skin hardening, and ulcerations. Furthermore, NVC abnormalities improved, and ulnar artery occlusion showed reperfusion on repeat testing. The present case suggests that hypoxemia-driven microvasculopathy may contribute to vascular occlusion and skin fibrosis observed in this atypical presentation.

Racial variability in immune responses only partially explains differential systemic sclerosis disease severity

ObjectiveTo understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients.Methods803 black and 2178...

Incidence of seropositive and seronegative rheumatoid arthritis in Denmark: a nationwide population-based study

Objective To investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition. Method This nationwide population-based cohort study was based on data from Danish healthcare and clinical quality registries between 2000 and 2018. Information on anti-cyclic citrullinated peptide and immunoglobulin M rheumatoid factor was obtained, and definitions of seropositivity according to the number of applied data sources were prespecified. Annual age- and sex-standardized IRs were calculated as the number of incident seropositive and seronegative cases, divided by the number of person-years (PY) in the general population in that given year. Results An increasing temporal trend in IR of seropositive RA and a decreasing trend in seronegative RA were observed. The IRs were higher for seropositive RA than for seronegative RA from 2009 onwards, with a widening of the IR gap between 2009 and 2016 regardless of the definition of seropositivity. When combining laboratory- and physician-reported autoantibody information and ICD-10 codes, the IR of seropositive RA in 2018 was approximately twice that of seronegative RA, at 19.0 and 9.0 per 100 000 PY, respectively. The level of antibody testing increased significantly during the study period. Conclusions The IR of seropositive RA increased over time, whereas the IR of seronegative RA decreased. Temporal IR changes may be caused by a real change in the RA serology subtypes, an increase in autoantibody testing and availability, changes in registration practice over time, or a combination of these factors.

Comparative assessment of the diagnostic performances of particle-based multianalyte technology and commercial ELISA for antiphospholipid autoantibody testing

Background: Diagnosing Antiphospholipid Syndrome (APS) relies heavily on laboratory findings, particularly the detection of specific antibodies like lupus anticoagulant (LA), IgG and/or IgM anti-cardiolipin (aCL), and IgG and/or IgM anti-β2 glycoprotein 1 (aB2GP1). Although ELISA is widely used in the US for this purpose, standardization between different assay methodologies remains challenging, leading to significant variability across laboratories. Particle-based multi-analyte technology (PMAT) offers a streamlined one-step detection for all six antiphospholipid (aPL) autoantibodies, covering aCL and aB2GP1 of IgA, IgG, and IgM isotypes. Methods: In this study involving 224 subjects, including 34 clinically diagnosed with APS, alongside 160 non-APS patients and 30 healthy donors, PMAT’s performance was evaluated against commercial ELISA in detecting aPL antibodies. Results: At the manufacturer’s suggested cutoff, PMAT exhibited sensitivity comparable to ELISA, albeit with a low to moderate decrease in specificity for certain antibodies. With anti-CL IgM alone, PMAT displayed a 17.7% decrease in sensitivity, accompanied by a corresponding 31.1% increase in specificity compared to ELISA. However, applying a stricter cutoff (88–90% specificity), IgA and IgM antibodies yielded 5.9–17.6% higher sensitivities with PMAT, and IgG antibodies displayed similar sensitivity. Conclusions: In this study cohort, PMAT demonstrated higher or comparable sensitivity to that of commercial ELISA for all six aPL antibodies at a specificity cutoff near 90%. Notably, PMAT demonstrated superior sensitivity and specificity overall in detecting IgA aCL and aB2GP1 antibodies. This study highlights the potential of automated PMAT for detecting aPL antibodies in APS evaluation.

AUTOIMMUNE ENCEPHALITIS: DIAGNOSTIC AND TREATMENT APPROACH

Autoimmune encephalitis is a type of brain inflammation induced by an inappropriate immune response to a neuronal antigen, resulting in the generation of autoantibodies. Autoimmunity as important cause of encephalitis in recent years has not been much reported in Indonesia. Increased familiarity with autoimmune encephalitis among physician, not only neurologist, is extremely important for early detection. Prompt diagnosis and early immunotherapy leads to better prognosis in this potentially treatable disease, despite a long disease course. Autoimmune encephalitis is characterized by acute-subacute progressive neuropsychiatric symptoms with associated cognitive dysfunction, encephalopathy, psychiatric disorders, movement disorders and seizures, with anti-N-methyl-D-aspartate (NMDA) receptors encephalitis as the most common type. In addition to clinical features, further diagnostic investigations needed are brain magnetic resonance imaging (MRI), electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, and autoantibody testing. Challenges in establishing diagnosis include wide range of clinical symptoms, absence of abnormalities in brain MRI, unspecified EEG findings, negative antibody testing, and limited availability of antibody testing in Indonesia. This literature review discusses the recognition, diagnosis and principle of treatment of autoimmune encephalitis.

A Bead-Based Nonradioactive Immunoassay for Autoantibody Testing in a Mouse Model of Myasthenia Gravis.

Serological testing for anti-acetylcholine receptor (AChR) autoantibodies is not only crucial for the diagnosing, disease monitoring, and treatment management of patients with myasthenia gravis (MG) but also for preclinical studies utilizing MG disease models. However, there are no specific guidelines on which methods to use in clinical diagnostic or research laboratories to detect or quantify any MG-specific autoantibodies. Conventional autoantibody assays, particularly those for anti-AChR antibodies, are varied and mostly laboratory-specific. Here, we report our new nonradioactive immunoprecipitation-immunoblotting method for assessing autoantibodies (anti-AChR antibodies) in a mouse model of MG. This simple, efficient, reproducible, and cost-effective assay appears superior to the enzyme-linked immunosorbent assay but comparable to the radioimmunoprecipitation or cell-based assay in specificity and sensitivity. Thus, the newly developed assay can serve as a valuable alternative to classical assays and is suitable for routine testing of AChR-specific autoantibodies in preclinical studies. The further optimization of our assay may facilitate its application in the diagnosis and therapeutic management of patients with MG.

Stress-Induced Diabetic Ketoacidosis Due to Transient Beta Cell Stunning in a Youth with Type 2 Diabetes Mellitus: A Case Report

Abstract A 15-year-old boy was admitted to the intensive care unit of our hospital with complaints of increased urination, extreme tiredness, and nausea for the past 15 days. He had also lost 6.5 kg of weight (almost 10% of total body weight) in 1 month. On admission, his plasma glucose was 780 mg/dL, glycated haemoglobin (HbA1c) 11.6%, serum ketones >10.0 mmol/L, osmolality 346 mosm/kg, arterial pH 7.28, and bicarbonate 9 mEq/L. The C-peptide report initially indicated poor pancreatic beta cell reserve (fasting: 0.41 pmol/mL and stimulated: 0.46 pmol/mL). He was diagnosed with diabetic ketoacidosis and responded well to treatment, after which time he was switched to subcutaneous insulin. Ten days later, in the outpatient clinic, his fasting blood glucose was 132 mg/dL, postprandial blood glucose was 183 mg/dL, and C-peptide had improved to fasting: 0.89 pmol/mL and stimulated: 1.42 pmol/mL. Considering the presence of acanthosis nigricans on the neck, a body mass index in the overweight range, a positive family history of diabetes, and negative tests for pancreatic autoantibodies, an early onset diagnosis of type 2 diabetes mellitus was considered. Insulin was gradually withdrawn, and he was switched to metformin. Sustained recovery of C-peptide in this case indicates that lack of insulin at admission was due to beta cell stunning, rather than a total and irreversible loss of beta cells as expected in type 1 diabetes mellitus. Beta cell stunning is often reversible, as shown in this case.

Thyroid dysfunction and autoantibodies in rheumatoid arthritis patients at King Saud Medical City: A retrospective cohort study

Abstract: BACKGROUND: Autoimmune thyroid diseases often coexist with conditions such as Sjögren’s syndrome and rheumatoid arthritis (RA). Studies have shown that patients with RA are at an increased risk of thyroid dysfunction. Studies conducted in Egypt and Jeddah have demonstrated a higher prevalence of thyroid dysfunction in patients with RA. This study aimed to determine the prevalence of thyroid dysfunction and its characteristics in patients with RA treated at a single center in Saudi Arabia. METHODS: This was a retrospective cohort study conducted at King Saud Medical City, Riyadh, Saudi Arabia. All patients with RA who qualified for the American Rheumatism Association criteria between 2016 and 2021 were eligible for inclusion. All patients underwent clinical examination and tests for thyroid function and RA-specific autoantibodies. The primary outcome was the presence or absence of thyroid disorders. RESULTS: A total of 158 RA patients were included. Eighty-five patients (53.8%) were seropositive, including 65 (41.1%) positive for rheumatoid factor and 58 (36.7%) positive for anti–citrullinated protein antibody. Erythrocyte sedimentation rate was elevated in 108 (72%) patients and 28 (19%) patients had significant Disease Activity Score (DAS 28). Vitamin D deficiency was observed in 100 patients (66.7%). Sixteen percent of patients in this cohort had hypothyroidism and 4.2% had hyperthyroidism. Vitamin D deficiency was associated with hyperthyroidism (2.1% vs. 8.9%, P = 0.048). Vitamin D deficiency was not significantly linked to seropositive RA (50% vs. 60%, P = 0.247) but was significantly associated with higher DAS 28 (15% vs. 30%, P = 0.030). CONCLUSION: Our study provides insights into thyroid patterns in Saudi Arabian patients with RA, highlighting the role of Vitamin D in thyroid disorders and disease activity. CATEGORIES: Internal Medicine, Rheumatology.

Criteria and non-criteria antiphospholipid autoantibodies screening in patients with late pregnancy morbidity: A cross-sectional study

IntroductionAntiphospholipid syndrome (APS) is a cause of pregnancy morbidity. We aim to determine the frequency of criteria and non-criteria anti-phospholipid (aPL) autoantibodies in patients admitted for unexplained fetal death (UFD), pre-eclampsia (PE) and/or fetal growth restriction (FGR). MethodsAll consecutive patients with UFD, PE and/or FGR followed in the department of Obstetrics, Bichat Hospital, University of Paris, Paris, between January 2019 and December 2021 were screened. Patients with available serum stored from the index pregnancy were included. Patients with previously known APS or twin pregnancy were excluded. Testing for aPL autoantibodies included anti-cardiolipin (aCL), anti-β2GPI (aβ2GPI), anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine/prothrombin (aPS/PT) IgG/IgM and anti-annexin V IgG. When available, placenta specimens were analyzed by a pathologist blinded to the aPL status. All clinical characteristics, pregnancy features, and comorbidities were extracted from electronic medical records. ResultsOverall 167 (32 (28.8–35.7) years) patients with UFD (n = 28; 16.8 %), PE (n = 60; 35.9 %) and/or FGR (n = 105; 62.9 %) were screened for aPL autoantibodies. Moderate titers of aPL autoantibodies were detected in 33 (n = 33/167, 19.8 %) patients. aPL autoantibodies were non-criteria aPE IgG/IgM in most cases (n = 28/33, 84.8 %). aPS/PT IgG/IgM were found in 11 (n = 11/33, 33.3 %) cases and aCL or aβ2GP1 IgG/IgM in 4 (n = 4/33, 12.1 %). Multivariable logistic regression showed that aPL autoantibodies were mostly associated with UFD (OR 4.37 [1.72–11.20], p = 0.002), PE ≤ 34th week of gestation (3.22 [0.86–11.90], p = 0.070) and chronic deciduitis (8.03 [0.89–67.2], p = 0.060) DiscussionThe frequency of aPL autoantibodies, mostly aPE, is high in patients with late pregnancy morbidity and may qualify obstetrical APS.

Clinical management of lupus in the United States: A claims-based analysis

ObjectivesTo understand the evaluation and management of patients coded with lupus in the broad clinical community in the United States. MethodsClaims data for diagnoses, procedures, medications, and physician specialties were evaluated for three lupus cohorts [lupus nephritis (LN), systemic lupus erythematosus excluding LN (SLE), and cutaneous lupus erythematosus excluding SLE and LN (CLE)] using the EVERSANA claims databases. Identification of patients was based upon the occurrence of lupus-specific codes, with the requirement that a single patient receive a lupus-related ICD code twice within a six-month period. ResultsUsing ICD codes, we were able to identify 28,372 patients coded with LN, 82,744 patients coded with SLE, and 13,920 patients coded with CLE, and subsequently evaluate the journey of patients in each group in the year before and after being coded as having a diagnosis of lupus. For the three lupus cohorts, the basis of diagnosis was not always apparent, as clinical features of lupus were not often obtained, autoantibody testing was not usual, biopsies were uncommon and subspecialty involvement was not routine. In addition, a significant increase in laboratory testing, non-lupus diagnoses, emergency department visits and cost during the year before receiving a lupus code suggested uncertainty in disease recognition. Nevertheless, these patients received two separate lupus coding events within a six-month period, supporting a sustained or repeated diagnosis of lupus by the evaluating clinicians. When compared, the three lupus cohorts differed with regard to frequency of laboratory testing, subspecialty care, skin and renal biopsies, and medication management. Moreover, there was an increase in the cost of care of patients coded with lupus compared to a reference patient population both during the year before and after being coded with a diagnosis of lupus. ConclusionThe data present a comprehensive report of the care of patients coded as having a diagnosis of lupus in the United States, including those outside of specialty centers. Despite the unclear basis of diagnosis in some patients, evaluation and management of patients coded as having a diagnosis of lupus in the general care community does not closely follow the recommended guidelines set forth by professional societies.

A Case Report of Integrative Treatment in a Type 2 Diabetes Patient with Multiple Symptoms and Evaluation Using Continuous Glucose Monitoring

Introduction: We describe the effects of Sosiho-tang decoction and insulin combination therapy, as well as the effect of integrated traditional Korean medicine therapy, using continuous glucose monitoring (CGM) in a diabetic patient complaining of a range of diabetic symptoms.Case report: A 24-year-old female presented with symptoms of diabetes, including weight loss, thirst, and polyuria, and was diagnosed with type 2 diabetes through blood tests, endocrine tests, and autoantibody tests. During hospitalization, the patient received insulin therapy and Sosiho-tang decoction concurrently, achieving normal blood glucose levels. After discharge, adhering to the Sosiho-tang decoction and CGM enabled the insulin dosage to be gradually reduced while maintaining normal blood glucose levels.Conclusion: Combination therapy with insulin and Sosiho-tang rapidly reduced hyperglycemia in the short term. CGM post-discharge allowed for observation of the patient’s blood glucose levels. Ultimately, Sosiho-tang medication lowered blood glucose levels, reduced insulin requirements, and facilitated a reduction in the insulin dosage.

Development of a clinical calculator to aid the identification of MODY in pediatric patients at the time of diabetes diagnosis

Maturity Onset Diabetes of the Young (MODY) is a young-onset, monogenic form of diabetes without needing insulin treatment. Diagnostic testing is expensive. To aid decisions on who to test, we aimed to develop a MODY probability calculator for paediatric cases at the time of diabetes diagnosis, when the existing “MODY calculator” cannot be used. Firth logistic regression models were developed on data from 3541 paediatric patients from the Swedish ‘Better Diabetes Diagnosis’ (BDD) population study (n = 46 (1.3%) MODY (HNF1A, HNF4A, GCK)). Model performance was compared to using islet autoantibody testing. HbA1c, parent with diabetes, and absence of polyuria were significant independent predictors of MODY. The model showed excellent discrimination (c-statistic = 0.963) and calibrated well (Brier score = 0.01). MODY probability > 1.3% (ie. above background prevalence) had similar performance to being negative for all 3 antibodies (positive predictive value (PPV) = 10% v 11% respectively i.e. ~ 1 in 10 positive test rate). Probability > 1.3% and negative for 3 islet autoantibodies narrowed down to 4% of the cohort, and detected 96% of MODY cases (PPV = 31%). This MODY calculator for paediatric patients at time of diabetes diagnosis will help target genetic testing to those most likely to benefit, to get the right diagnosis.

Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study.

Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease. We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes. The average age at diagnosis was 45.93 ± 4.62 years (range: 11-72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on 18F-fluorodeoxyglucose positron-emission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up. The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis.

How to Perform Autoantibody Testing for Autoimmune and Inflammatory Diseases of Peripheral Nerves and Muscles

Measurement of autoantibodies is essential for the management of several peripheral nerve and muscle diseases. The clinical significance of autoantibody testing differs for each antibody. In addition, clinicians must understand several issues including the accuracy of the test, isotype and subclass distribution, and its relationship to disease activity. Moreover, many autoantibody tests are not covered by health insurance. With limited medical resources, clinicians are required to be up-to-date with the latest information to utilize test results in daily practice without misunderstanding.

Generation of type I interferon autoantibody tests for at-risk populations

Abstract A plethora of evidence has shown that 10-20% of cases of severe COVID-19 occur in individuals harboring autoantibodies that neutralize type I interferons (IFNs) and thus block their ability to initiate innate defenses and dampen viral replication. These autoantibodies are, therefore, currently the strongest and most common determinants of a growing range of severe viral diseases, especially in the elderly; yet, no routine test is available to the general population to gain knowledge of their immune insufficiency and potential risk from future infections. Here, we developed a set of assays to establish the levels of anti-IFN autoantibodies and their neutralizing activity and performed validation studies in a cohort of hospitalized COVID patients (N=388) to assess their sensitivity and specificity. Consistent with previous findings, our tests developed in a CLIA-certified laboratory were able to detect anti-IFN autoantibodies in a sizable fraction of patients with severe and critical COVID-19 pneumonia. Taken together, our results suggest that anti-IFN autoantibody testing should be considered for standard clinical screening.

FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review

BackgroundIn recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare.Case presentationHere, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response.ConclusionsOur case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.

P150 Diagnostic utility of anti-cN1A autoantibody testing in sporadic inclusion body myositis

Abstract Background/Aims Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients aged over 50 years. Diagnostic criteria encompass clinical, biochemical, and myopathological features. Certain myopathological features possess high specificity but low sensitivity; reliance on such findings may lead to delayed or misdiagnoses. The discovery of autoantibodies against cytosolic 5'-Nucleotidase 1A (cN1A) in sIBM patients suggests an autoimmune component in pathogenesis, but the inclusion of this autoantibody in diagnostic criteria remains uncertain. Additionally, optimal testing methodology has not been established, with varying techniques (e.g., ELISA/line-blot) in use. We assessed antibody profiles in an sIBM cohort and reviewed diagnoses in anti-cN1A positive patients. Methods This study was based at the Northern Care Alliance NHS Foundation Trust which hosts a tertiary neuromuscular referral service for the North-West of England. Data sources included myositis clinic and immunology results databases. All patients tested using a validated myositis line-blot immunoassay (EUROLINE 16 Antigen et cN1A [EUROIMMUN]) November 2021-April 2023 were included. Diagnoses of all tested patients were identified through case-note review. Sensitivity and specificity metrics were calculated based on diagnosis and anti-cN1A antibody status. Results The total number of patients tested for anti-cN1A was 495. Of these, 10 patients had a diagnosis of sIBM. The true-positive and false-negative rates were both 50% (n = 5 each). Of the 485 patients who did not have sIBM, true-negativity was 97.52% (n = 473) and false-positivity 2.47% (n = 12). Overall, anti-cN1A had a sensitivity of 50%, specificity of 97.52%, positive predictive value of 29.41% and negative predictive value of 98.95% for sIBM (Table 1). Patients with a false-positive anti-cN1A antibody had diagnoses of: primary Raynaud’s (n = 5); undifferentiated CTD (n = 3); systemic sclerosis (n = 2); non-sIBM myositis (n = 2). Conclusion Anti-cN1A detected using the EUROLINE 16 Antigen assay has high specificity but lacks sensitivity for sIBM, consistent with previous literature. These findings suggest that this assay performs similarly to other cN1A detection methodologies and has utility in confirming the diagnosis of sIBM where there is clinical suspicion. Further real-world analysis of antibody data in larger cohorts is required to clarify the role of serological testing in sIBM diagnostic criteria, to improve diagnostic delays and misclassifications. Disclosure M. Al-Attar: None. T. Khoo: None. J.B. Lilleker: None. H. Chinoy: None.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with “idiopathic” interstitial lung disease

BackgroundAutoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. Methods499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. Results2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. ConclusionSpecific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Clinical Significance of Uncommon, Non-Clinical, and Novel Autoantibodies.

Autoantibodies are a common mark of autoimmune reaction and their identification in the patients' serum, cerebrospinal fluid, or tissues is generally believed to represent diagnostic or prognostic biomarkers of autoimmune diseases or autoinflammatory conditions. Traditionally, autoantibody testing is an important part of the clinical examination of suspected patients, and in the absence of reliable T cell tests, characterization of autoantibody responses might be suitable in finding causes of specific autoimmune responses, their strength, and sometimes commencement of autoimmune disease. Autoantibodies are also useful for prognostic stratification in clinically diverse groups of patients if checked repeatedly. Antibody discoveries are continuing, with important consequences for verifying autoimmune mechanisms, diagnostic feasibility, and clinical management. Adding newly identified autoantibody-autoantigen pairs to common clinical laboratory panels should help upgrade and harmonize the identification of systemic autoimmune rheumatic disorders and other autoimmune conditions. Herein, we aim to summarize our current knowledge of uncommon and novel autoantibodies in the context of discussing their validation, diagnostic practicability, and clinical relevance. The regular updates within the field are important and well justified.