Evaluation of a Ten-Antigen Immunodot Test in Autoimmune Hepatitis and Primary Biliary Cholangitis: Lessons Learned for a Tertiary Care Academic Hospital.

Autoimmune diseases of the liver and biliary tract require timely and accurate diagnosis. This study evaluates the D-tek panel (D-Tek, Mons, Belgium) of 10 immunodot antigens for its effectiveness in diagnosing autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). We retrospectively analysed serum samples from 111 patients who had undergone routine testing, including indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA), to confirm or exclude autoimmune liver or biliary tract disease. The panel tested for M2/nPDC, M2/OGDC-E2, M2/BCOADC-E2, M2/PDC-E2, gp210, sp100, LKM1, LC1, SLA, and F-actin antigens. Results showed that all positive IIF+ELISA results were confirmed by the immunodot panel, except for two samples from patients who had never been diagnosed with AIH. The immunodot test identified over 20 additional autoantibodies in samples initially negative by IIF, corroborated by laboratory imaging and medical history. The immunodot technique proved to be a quick, sensitive, and specific method with high overall accuracy. This study suggests that the immunodot technique may be an effective screening and confirmatory method for autoimmune liver diseases, potentially improving diagnostic efficiency and accuracy in clinical practice.

Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy.

OBJECTIVE: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. METHODS: Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician's Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. RESULTS: Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (ß = 3.830; p < 0.0001), muscle VAS (ß = 2.893; p < 0.0001), MMT8 (ß=-19.368; p < 0.0001), and creatine kinase (CK) levels (ß = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (ß = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). CONCLUSION: In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis.

Autoimmune Diseases Following Environmental Disasters: A Narrative Review of the Literature.

Environmental disasters are extreme environmental processes such as earthquakes, volcanic eruptions, landslides, tsunamis, floods, cyclones, storms, wildfires and droughts that are the consequences of the climate crisis due to human intervention in the environment. Their effects on human health have alarmed the global scientific community. Among them, autoimmune diseases, a heterogeneous group of disorders, have increased dramatically in many parts of the world, likely as a result of changes in our exposure to environmental factors. However, only a limited number of studies have attempted to discover and analyze the complex association between environmental disasters and autoimmune diseases. This narrative review has therefore tried to fill this gap. First of all, the activation pathways of autoimmunity after environmental disasters have been analyzed. It has also been shown that wildfires, earthquakes, desert dust storms and volcanic eruptions may damage human health and induce autoimmune responses to inhaled PM2.5, mainly through oxidative stress pathways, increased pro-inflammatory cytokines and epithelial barrier damage. In addition, it has been shown that heat stress, in addition to increasing pro-inflammatory cytokines, may also disrupt the intestinal barrier, thereby increasing its permeability to toxins and pathogens or inducing epigenetic changes. In addition, toxic volcanic elements may accelerate the progressive destruction of myelin, which may potentially trigger multiple sclerosis. The complex and diverse mechanisms by which vector-borne, water-, food-, and rodent-borne diseases that often follow environmental diseases may also trigger autoimmune responses have also been described. In addition, the association between post-disaster stress and the onset or worsening of autoimmune disease has been demonstrated. Given all of the above, the rapid restoration of post-disaster health services to mitigate the flare-up of autoimmune conditions is critical.

Aquaporin4-IgG seropositivity significantly increases the risk of comorbid autoimmune diseases in NMOSD patients: population-based registry data.

BACKGROUND: The aim of our study was to estimate the frequency of autoimmune comorbidities, in NMOSD patients from the national Serbian NMOSD Registry. METHODS: Our study comprises 136 patients with NMOSD, diagnosed according to the NMOSD criteria 2015. At the time of the study, in the Registry were collected demographic and clinical data, including those related to the coexisting comorbidities and pathogenic autoantibodies. Not all patients were tested for all autoimmune antibodies. None of the seronegative aquaporin4-IgG (AQP4-IgG) NMOSD patients, included in the Registry, were positive for the myelin oligodendrocyte glycoprotein IgG. RESULTS: Among 136 NMOSD patients, 50 (36.8%) had at least one associated autoimmune disorder. AQP4-IgG was present in the sera from 106 patients (77.9%), the proportion of NMOSD patients with autoimmune comorbidities being significantly higher in the AQP4-IgG positive subgroup in comparison to the AQP4-IgG negative (p = 0.002). AQP4-IgG seropositive NMOSD patients had 5.2-fold higher risk of comorbid autoimmune diseases (OR = 5.2, 95% CI 1.4-18.5, p = 0.012). The most frequently reported diseases were autoimmune thyroid disease (15.4%), Sjogren's syndrome (11.0%), systemic lupus erythematosus (5.1%), myasthenia gravis (4.4%), and primary antiphospholipid antibody syndrome (2.9%). Antinuclear antibodies (ANAs) were frequently detected in the subgroup of NMOSD patients tested for this antibody (50/92; 54.3%). The higher frequency of ANAs and anti-extractable nuclear antigen autoantibodies, in the subgroups of AQP4-IgG-positive patients compared to the AQP4-IgG negative, tested for these antibodies, was statistically significant (p = 0.009, and p = 0.015, respectively). CONCLUSION: In conclusion, based on our results, in a defined cohort with European ethnical background, a wide spectrum of autoimmune diseases is frequently associated with AQP4-IgG seropositive NMOSD patients.

Clinical presentations and antibody mechanisms in anti-IgLON5 disease.

Anti-IgLON5 disease is a rare neurological disease, identified just ten years ago, where autoimmunity and neurodegeneration converge. The heterogeneity of symptoms, sometimes mimicking pure neurodegenerative diseases or motor neuron diseases, in addition to lack of awareness, represents a diagnostic challenge. Biomarkers of neuronal damage in combination with in vivo visualization of tau deposition using positron emission tomography (PET) scanning could represent a major advance in monitoring disease progression. Recent studies with more autopsies available have helped refine the knowledge of the pathological features of the disease and strengthen the autoimmune hypothesis of the disease. Although the pathogenesis of anti-IgLON5 disease remains unclear, the irreversible antibody-mediated decrease of IgLON5 clusters from the cell surface and alterations produced in the cytoskeleton, as well as the behavioural abnormalities and signs of neuroinflammation and neurodegeneration observed in the brains of animals infused with antibodies from patients by passive transfer, which have recently been published, support the autoimmune hypothesis of the disease. This review aims to summarize these important aspects and recent advances in the pathophysiology of anti-IgLON5 disease.

Type 1 diabetes, celiac disease, and autoimmune thyroiditis autoantibodies in population-based type 2 diabetes patients.

Aims: The study aims were to determine autoantibodies associated with type 1 diabetes (T1D), celiac disease (CD) and autoimmune thyroid disease (AITD) in individuals living with type 2 diabetes (T2D) compared to T1D and matched controls. Methods: Individuals with T1D and T2D were randomly identified in health-care registers. Blood was collected through home-capillary sampling and autoantibodies associated with either T1D against glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), CD against tissue transglutaminase (tTGA) or AITD against thyroid peroxidase (TPOA) were determined in an automated, multiplex Antibody Detection by Agglutination-PCR (ADAP) assay. Results: GADA were detected in 46 % (88/191) of T1D and increased to 6.2 % (23/372) in T2D compared to 2.6 % (7/259) of controls (p = 0.0367). tTGA was low (1.1-2.6 %) and not different in between the study cohorts, nonetheless, in T1D tTGA was associated to islet autoantibodies. TPOA was more frequent in T1D, 27.1 % (53/191), compared to either T2D, 14.8 % (55/372; p = 0.0002) or controls, 14.3 % (37/259) (p = 0.0004). Overall, TPOA was more frequent in GADA positive (34.8 %; 8/23) than negative (13.5 %; 47/349; p = 0.0053) T2D individuals. Conclusion: It's suggested that analyzing GADA and TPOA may refine the autoimmune landscape in individuals clinically classified as T2D.

Antipolyphosphate monoclonal antibodies derived from autoimmune mice.

Background: Inorganic polyphosphates (polyPs) are linear chains of phosphates that accelerate blood clotting. Targeting polyP in vivo has been shown to reduce thrombosis. Objectives: To identify and characterize anti-polyP monoclonal antibodies that could be used as analytical tools and as antithrombotic agents. Methods: Hybridomas were prepared from spleen cells from autoimmune NZBWF1/J female mice and screened for anti-polyP antibodies. Antibodies that bound polyP using enzyme-linked immunosorbent assay and pull-down assays were further characterized with plate binding, surface plasmon resonance, and plasma-based clotting assays. Antithrombotic potential was evaluated in a murine ferric chloride-induced carotid artery thrombosis model. Results: Of 4 antibodies that bound polyP in our pull-down assay, 2 (PP2069 and PP2099) were available for further characterization. While analyzing these anti-polyP antibodies, we found secretory leukocyte peptidase inhibitor (SLPI) to be a common contaminant of these antibodies and that SLPI binds polyP. We removed SLPI quantitatively from our purified immunoglobulin G. Both PP2069 and PP2099 immunoglobulin G displayed high affinity for polyP but also bound to other polyanions such as DNA, heparin, and certain other glycosaminoglycans, indicating limited specificity. Both antibodies inhibited polyP-initiated plasma clotting in vitro. When tested in vivo in a mouse thrombosis model, however, neither PP2069 nor PP2099 exhibited a significant antithrombotic effect. Conclusion: Autoimmune mice spontaneously produce antibodies against polyP. The 2 examples of anti-polyP monoclonal antibodies studied here not only bound to polyP with high affinity but also cross-reacted with DNA and heparin. Neither antibody protected against thrombosis in a mouse model, but they might have some utility for in vitro studies of polyP.

Tlr7 drives sex- and tissue-dependent effects in Sjögren's disease.

Primary Sjögren's disease (pSD) is a systemic autoimmune disease that has the strongest female predilection of all autoimmune diseases. The underlying mechanisms that govern this sexual dimorphism, however, remain poorly understood. We hypothesized that pSD females would exhibit more robust disease as compared to males, and that Tlr7 controls distinct disease manifestations in males and females. Using a well-established pSD mouse model, we harvested exocrine glands, and pulmonary and renal tissue from males and females and quantified the inflammation present. We then collected salivary glands, spleens, and cervical lymph nodes and performed flow cytometry to assess immune populations implicated in disease. We also harvested sera to examine total and autoreactive antibodies. Our data revealed that pSD mice displayed sex-biased disease, as pSD females showed decreased dacryoadenitis, but increased nephritis as compared to males. Moreover, females exhibited increased proportions of germinal center B cells and CD4+ activated/memory T cells in the periphery. Additionally, salivary gland immune populations were altered in a sex-dependent manner in pSD. Females with pSD also displayed elevated total and autoreactive IgG as compared to males. Additionally, splenic B cell Tlr7 expression was increased in females. We next generated pSD mice that lacked Tlr7 systemically and found that ablation of Tlr7 was primarily protective in pSD females, while Tlr7-deficient pSD males showed heightened disease. Thus, pSD mice display sex-biased disease and these dichotomous manifestations are governed by Tlr7 activation. This study identifies Tlr7 as a druggable target for pSD, and highlights the importance of studying pSD disease mechanisms in both sexes.

A case of corticobasal syndrome possibly associated with anti-Yo antibodies.

INTRODUCTION: Corticobasal syndrome (CBS) is a rare form of atypical parkinsonism, most commonly caused by neurodegenerative disorders. Autoimmune underlying conditions are extremely rare, and anti-Yo antibody-associated CBS has not been reported yet. CASE REPORT: Herein, we describe a case of a 68-year-old woman presenting with progressive dysarthria, gait instability and difficulty using her left hand with subacute deterioration during the last three months. Neurological examination revealed asymmetrical parkinsonism and pyramidal syndrome, reflex myoclonus and dystonia of her left upper limb, accompanied by apraxia of her left lower limb, fulfilling the criteria for possible CBS. Neuroimaging showed asymmetric frontoparietal atrophy, while cerebrospinal fluid and dopamine transporter imaging were normal. Prior to our evaluation, antineuronal autoantibody testing indicated positive anti-Yo antibodies. There was mild improvement after second IVIG cycle, and further investigation revealed no tumor. CONCLUSION: Although autoimmune etiology of this case cannot be certain, it highlights the potential expansion of the clinical spectrum of anti-Yo-associated paraneoplastic syndrome.

Relationship between clinical manifestations and serological profile in patients affected by Systemic Lupus Erythematosus.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies. Objectives: To evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data. Methods: A retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies - ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher's exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant. Results: One-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia. Conclusions: In our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.

A comparative study of anti-ADAMTS-13 antibody dynamics in immune-mediated thrombotic thrombocytopenic purpura.

Background: Thrombotic thrombocytopenic purpura, particularly its immune-mediated variant (iTTP), necessitates accurate diagnostic approaches for effective management. Objectives: To compare a chemiluminescence immunoassay (CLIA) and an enzyme-linked immunosorbent assay (ELISA) for testing ADAMTS-13 activity and detecting anti-ADAMTS-13 autoantibodies (AAbs) in patients with iTTP. Methods: This study involved 31 paired samples from 12 iTTP patients. ADAMTS-13 activity was measured using the HemosIL AcuStar (Instrumentation Laboratory, CLIA) and Technozym (Technoclone) activity assay (ELISA). The presence of AAbs was assessed using Technozym ADAMTS-13-INH assay (ELISA) and HemosIL AcuStar activity (CLIA) within a Bethesda assay following mixing with normal pool plasma. von Willebrand factor (VWF) multimers were analyzed using the HYDRASYS-2 SCAN system and the HYDRAGEL 5- or 11-VW Multimer kits (Sebia). VWF activity levels were measured with the HemosIL AcuStar VWF:GPIbR on the ACL AcuStar Analyzer (IL). Results: For ADAMTS-13 activity, a strong linear relationship and no bias between CLIA and ELISA were confirmed (slope = 1.01 [0.91, 1.11], intercept = 0.00 [-0.47, 0]). However, significant discrepancies were found in AAb detection during remission phases with ADAMTS-13 activity between 10% and 50%, with CLIA and ELISA showing significant divergence (P < .001, Cohen's g = 0.34). Consistently, VWF multimers and activity levels exhibited significantly different values between remission samples with ADAMTS-13 activity below 50% and above 50%. In longitudinal analysis of patients with multiple iTTP relapses, positivity to CLIA appears to precede ELISA in predicting exacerbations. Conclusion: While CLIA and ELISA might be interchangeable for assessing ADAMTS-13 activity, they are not equivalent for detecting AAbs, particularly in patients in clinical remission with ADAMTS-13 activity between 10% and 50%.

Utility of common investigations for suspected inflammatory arthritis in adults.

Inflammatory arthritis may be the principal feature or one component of an inflammatory rheumatological disease. It is a clinical diagnosis, principally made based on the patient's history and examination. Specific investigations, such as rheumatoid factor and human leucocyte antigen B27 gene, may support the diagnosis in the context of a suggestive clinical presentation, but a diagnosis cannot be made based on these tests alone because positive results may also be seen in healthy individuals. To reduce the likelihood of false positive results, laboratory and radiological investigations should be tailored to the suspected diagnosis based on pretest probability. While musculoskeletal symptoms are a common presentation in general practice, specific features that increase suspicion of an inflammatory arthritis include prolonged morning stiffness (more than 1 hour) that is improved by exercise or movement. A broad 'rheumatological panel' increases the likelihood of false positive results and should be avoided to prevent unnecessary further investigations and treatment, and unwarranted anxiety in both the patient and the doctor.

Screening for autoimmune diseases in apparently healthy antinuclear antibody positive individuals.

Background: Anti-nuclear antibodies (ANA) assessed by immunofluorescence (IF) microscopy are associated with systemic autoimmune rheumatic diseases (SARD) and can be detected years before onset of clinical symptoms. Recent data indicate dysregulation of the immune system with increased levels of proinflammatory cytokines, including type I interferons (IFN), in ANA-positive versus ANA-negative individuals. Herein, the aims were to investigate IF-ANA, ANA fine specificities, and IFN-α protein levels in relation to self-reported symptoms, as well as clinical signs, of SARD in a large group of healthy blood donors (HBD). Methods: Sera from 825 HBD (48.8% females) were included. IF-ANA was assessed, using HEp-2 cells, according to the routine at the accredited laboratory of Clinical Immunology, Linköping University Hospital. All samples were analyzed for IgG-ANA fine specificities using addressable laser bead assay (ALBIA) at the same laboratory. IFN-α was determined using ELISA. Antibody-positive individuals, and their sex- and age-matched antibody-negative controls, were asked to fill a questionnaire regarding symptoms associated with SARD. Results: In total, 130 HBD (15.8%) were positive with IF-ANA and/or ALBIA. Anti-U1RNP was significantly more common among women. Generally, self-reported symptoms correlated poorly with IF-ANA and/or ALBIA results. Two females with high levels of Ro60/SSA, Ro52/SSA and IFN-α reported mild sicca symptoms and were diagnosed with Sjögren's disease after clinical evaluation. Conclusion: A considerable proportion of apparently HBD are autoantibody positive, but without clear association to self-reported symptoms. Nevertheless, the combination of autoantibodies, relevant symptoms and high IFN-α levels identified the small proportion of individuals with SARD in the study population.

Autoantibodies in cancer: a systematic review of their clinical role in the most prevalent cancers.

Although blood autoantibodies were initially associated with autoimmune diseases, multiple evidence have been accumulated showing their presence in many types of cancer. This has opened their use in clinics, since cancer autoantibodies might be useful for early detection, prognosis, and monitoring of cancer patients. In this review, we discuss the different techniques available for their discovery and validation. Additionally, we discuss here in detail those autoantibody panels verified in at least two different reports that should be more likely to be specific of each of the four most incident cancers. We also report the recent developed kits for breast and lung cancer detection mostly based on autoantibodies and the identification of novel therapeutic targets because of the screening of the cancer humoral immune response. Finally, we discuss unsolved issues that still need to be addressed for the implementation of cancer autoantibodies in clinical routine for cancer diagnosis, prognosis, and/or monitoring.

Modified radioimmunoassay versus ELISA to quantify anti-acetylcholine receptor antibodies in a mouse model of myasthenia gravis.

In mouse models of myasthenia gravis (MG), anti-acetylcholine receptor (AChR) antibodies can be quantified to monitor disease progression and treatment response. In mice, enzyme-linked immunosorbent assay (ELISA) is the gold standard to quantify these antibodies. However, this method requires antigen purification, which is both time-consuming and expensive. In humans, radioimmunoassay (RIA)-which is more sensitive than ELISA-is commonly used to quantify AChR antibodies. At present, however, no commercial RIA kits are available to quantify these antibodies in mice. The aim of this study was to compare a modified commercial human RIA kit to two ELISA methods to detect AChR antibodies in an experimental autoimmune mouse model of MG (EAMG). C57BL/6 J mice were immunized with purified AChR from Tetronarce californica (T-AChR). Serum samples were analyzed by RIA and two ELISAs (T-AChR and purified mouse AChR peptide [m-AChR]). The modified RIA showed excellent sensitivity (84.1 %) and specificity (100 %) for the detection of AChR antibodies. RIA showed a good agreement with T-AChR ELISA (κ = 0.69) but only moderate agreement with m-AChR ELISA (κ = 0.49). These results demonstrate the feasibility of modifying a commercially-available RIA kit to quantify AChR antibodies in EAMG. The advantage of this technique is that it eliminates the need to develop the entire methodology in-house and reduces inter and intra-laboratory variability.

Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials. Individuals at risk of RA can be identified through population screening, referrals to musculoskeletal programmes and by recognition of arthralgia suspicious for RA. Clinical trials in individuals at risk for future clinical RA have demonstrated that limited courses of corticosteroids, atorvastatin and hydroxychloroquine do not alter incidence rates of clinical RA; however, rituximab delays clinical RA onset, and methotrexate has transient effects in individuals who are anticitrullinated protein antibody-positive with subclinical joint inflammation identified by imaging. Abatacept delays clinical RA onset but does not fully prevent onset of RA after treatment cessation. Additionally, subclinical joint inflammation and symptoms appear responsive to interventions such as methotrexate and abatacept. To advance prevention, next steps include building networks of individuals at risk for RA, to improve risk stratification for future RA and to understand the biological mechanisms of RA development, including potential endotypes of disease, which can be targeted for prevention, thus adopting a more precision-based approach. Future trials should focus on interceptions aimed at preventing clinical RA onset and which treat existing symptoms and imaging-defined subclinical inflammation. These trials may include advanced designs (eg, adaptive) and should be combined with mechanistic studies to further define pathophysiological drivers of disease development.

Impact of autoantibodies against myelin oligodendrocyte glycoprotein in paediatric acquired demyelinating disease: Intellectual functioning and academic performance.

Paediatric acquired demyelinating syndromes (pADS) attack white matter pathways in the brain during an important period of development. Affected children can experience poor functional outcomes, including deficits in specific cognitive domains. Understanding risk factors for poor outcome will guide clinical management of these children. One clinical phenotype which may differentially impact cognitive outcomes is the presence of autoantibodies to myelin oligodendrocyte glycoprotein (MOG). Preliminary research has suggested that cognitive difficulties exist in paediatric patients who test positive for MOG antibodies or MOGAD (Myelin Oligodendrocyte Glycoprotein Associated Disease) however, they experience a less severe profile compared to seronegative counterparts. The current study assesses children diagnosed with pADS who tested positive or negative for MOG-ab using standardised assessments of both intellectual functioning and academic ability. The results show that a subset of MOGAD patients experience clinically significant sequalae in intellectual functioning and academic ability. The neuropsychological profile also differed between children with and without MOG-ab positivity, with seronegative patients more likely to show a clinically relevant difficulties at the individual patient level. Whilst no differences existed at the group-level; the current study demonstrates the relative additional risk of intellectual/academic difficulty associated with MOG-ab seronegativity. This research further supports the growing perspective that MOG-positivity confers a more favourable neuropsychological outlook than is the case for their seronegative counterparts. This broadening consensus offers reassurance for clinicians, families, and patients.

Potential prognostic value of rheumatoid factor in anti-aquaporin 4-immunoglobin G-positive neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is the central nervous system demyelinating disease differentiated from multiple sclerosis by the presence of anti-aquaporin 4-antibody (AQP4-ab), which is sometimes accompanied by non-organ-specific autoantibodies. METHODS: We prospectively collected clinical information and profiles of non-organ-specific autoantibodies such as fluorescent antinuclear (FANA), anti-Sjögren's syndrome A (SSA)/Ro, anti-SS B (SSB)/La, anti-neutrophil cytoplasmatic (ANCA), lupus anticoagulant (LA), anti-cardiolipin (ACA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), anti-thyroperoxidase, and anti-thyroglobulin antibodies in patients with NMOSD. Clinical characteristics and laboratory findings of patients with NMOSD with or without autoantibodies were analyzed. Cox proportional hazard models were used to identify independent risk factors predicting high disability in patients with NMOSD. RESULTS: A total of 158 patients with NMOSD (Female: Male = 146:12; age, 36.11 ± 14.7) were included. FANA was observed most frequently (33.3 %), followed by anti-SSA (28.6 %), anti-SSB (10.0 %), RF (8.5 %), anti-dsDNA (7.0 %), LA (4.7 %), ACA (4.8 %), and ANCA (2.4 %). High disability (Expanded Disability Status Scale (EDSS) score ≥ 6) was observed more frequently in patients with RF (45.5 %) than in those without RF (14.5 %) (p = 0.02). RF was a significant predictive factor for the high disability (hazard ratio [HR], 3.763; 95 % confidence interval [CI], 1.086-13.038; p = 0.037), age at onset (HR, 1.093; 95 % CI, 1.05-1.14; p ≤0.001), and annual relapse rate (ARR) (HR, 4.212; 95 % CI, 1.867-9.503; p = 0.001). CONCLUSION: Organ-specific and non-organ-specific autoantibodies are frequently observed in Korean patients with AQP4-ab-positive NMOSD. RF may be an independent predictor of high disability, along with age at onset and ARR.