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Objective: Late-onset systemic lupus erythematosus (LO-SLE) is defined as SLE diagnosed at age 50 years or later. Current studies on LO-SLE are small and have conflicting results. Methods: Using a large, electronic health record (EHR)-based cohort of SLE individuals, we compared demographics, disease characteristics, SLE-specific antibodies, and medication prescribing practices in LO ( n = 123) vs. NLO-SLE ( n = 402) individuals. Results: The median age (interquartile range) at SLE diagnosis was 60 (56-67) years for LO-SLE and 28 (20-38) years for NLO-SLE. Both groups were predominantly female (85% vs. 91%, p = 0.10). LO-SLE individuals were more likely to be White than NLO-SLE individuals (74% vs. 60%, p = 0.005) and less likely to have positive dsDNA (39% vs. 58%, p = 0.001) and RNP (17% vs. 32%, p = 0.02) with no differences in Smith, SSA, and SSB. Autoantibody positivity declined with increasing age at SLE diagnosis. LO-SLE individuals were less likely to develop SLE nephritis (9% vs. 29%, p < 0.001) and less likely to be prescribed multiple classes of SLE medications including antimalarials (90% vs. 95%, p = 0.04), azathioprine (17% vs. 31%, p = 0.002), mycophenolate mofetil (12% vs. 38%, p < 0.001), and belimumab (2% vs. 8%, p = 0.02). Conclusion: LO-SLE individuals may be less likely to fit an expected course for SLE with less frequent positive autoantibodies at diagnosis and lower rates of nephritis, even after adjusting for race. Understanding how age impacts SLE disease presentation could help reduce diagnostic delays in SLE., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Severe asthma (SA) has heterogeneous inflammatory phenotypes characterized by persistent airway inflammation (eosinophilic and/or neutrophilic inflammation) and remodeling. Various immune cells (eosinophils, neutrophils, and macrophages) become more activated and release inflammatory mediators and extracellular traps, damaging the protective barrier of airway epithelial cells and further activating other immune and structural cells. These cells play a role in autoimmune responses in asthmatic airways, where the adaptive immune system generates autoantibodies, inducing immunoglobulin G-dependent airway inflammation. Recent studies have suggested that adult asthmatics had high titers of autoantibodies associated with asthma severity, although pathogenic factors or diagnostic criteria are not well-defined. This challenge is further compounded by asthmatics with the autoimmune responses showing therapy insensitivity or failure to current pharmacological and biological treatment. This review updates emerging mechanisms of autoimmune responses in asthmatic airways and provides insights into their roles, proposing potential biomarkers and therapeutic targets for SA., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Purpose: Optic neuritis (ON) is a relatively common ophthalmic disease that has recently received renewed attention owing to immunological breakthroughs. We studied the profile of patients with ON with special reference to antibody-mediated ON and the challenges faced in its management., Methods: Case records of patients with ON presenting to a tertiary eye-care center in South India were analyzed. Data on demographics, presenting visual acuity (VA), clinical features, seropositivity for aquaporin-4 immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), details of magnetic resonance imaging (MRI) of orbits and brain, and treatment were collected., Results: Among 138 cases with acute ON, male: female ratio was 1:2. Isolated ON was present in 41.3% of cases. Antibody testing of sera was performed in 68 patients only due to financial limitations. Among these, 48.5% were MOG-IgG-seropositive, 11.76% were AQP4-IgG-seropositive, and 30.88% samples were double seronegative. Other causes included multiple sclerosis (n = 4), lactational ON (n = 4), tuberculosis (n = 2), invasive perineuritis (n = 2), COVID-19 vaccination (n = 2), and COVID-19 (n = 1). The mean presenting best corrected visual acuity (BCVA) was 1.31 ± 1.16 logMAR (logarithm of the minimum angle of resolution). The mean BCVA at 3 months was 0.167 ± 0.46 logMAR. Only initial VA ≤ 'Counting fingers' (CF) had a significant association with the visual outcome for final VA worse than CF. The steep cost of investigations and treatment posed challenges for many patients in the management of ON., Conclusion: MOG-IgG-associated ON is common in India. Unfortunately, financial constraints delay the diagnosis and timely management of ON, adversely affecting the outcome., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated neuroinflammatory disease of the central nervous system. Patients typically present with sensory deficits, weakness, and incontinence. This is a case of a 43-year-old female with diabetes mellitus admitted for acute onset leg weakness and stool incontinence. Spinal MRI imaging revealed transverse myelitis, and her lab work was significant for an anti-aquaporin 4 (AQP4) antibody titer of 1:2,560. Initial treatment consisted of a high-dose steroid taper and plasmapheresis. This unique case illustrates the importance in recognizing delayed presentations of rare neuroinflammatory conditions previously assumed to be a sequela of diabetic neuropathy.

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients' well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 35 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies., Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT05045820., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Pucka, Debats, Reyes, Syed, O’Brien, Mehta, Manchanda, Jacob, Hardesty, Greist, Harte, Harris, Yu and Wang.)

Mucous membrane pemphigoid (MMP) is a rare, immune-mediated, vesiculobullous disease that predominantly affects the oral cavity and conjunctiva. In MMP, autoantibodies are directed against hemidesmosomal proteins in the basement membrane zone, most commonly BP180. Clinical signs and symptoms include gingival desquamation, erosions, and ulcerations. Differential diagnoses include other immune-mediated blistering diseases, such as bullous pemphigoid. Definitive diagnosis is reached through history taking, physical examination, tissue biopsy and/or serology testing. MMP, although not curable, is typically managed with topical or systemic corticosteroids, in addition to immunosuppressive therapies and biologic agents in recalcitrant cases. Untreated MMP can lead to life-threatening complications, such as blindness. As a condition that affects the oral cavity, it is important that dentists understand how to recognise, diagnose and manage the disease., (© 2024. The Author(s), under exclusive licence to the British Dental Association.)

We report the case of a 45-year-old man who was diagnosed with clinically amyopathic dermamyositis (CADM) and interstitial lung disease (ILD) after presenting with skin lesions typical of CADM and testing positive for anti-Melanoma Diferentiation-Associated gene 5 (anti-MDA5) anti-bodies. He was treated with a regimen including steroid pulse therapy, intravenous cyclophosphamide (IVCY), and calcineurin Inhibitor drug, which initially improved his ILD. However, three months post-treatment, the first deterioration of his conditions occurred, necessitating further administration of steroid pulse therapy and IVCY. After eight cycles of IVCY therapy, the serum levels of KL-6 and anti-MDA5 antibodies decreased, and reaching their lowest values. Nevertheless, two years and six months after the first observed deterioration, the second deterioration of his conditions occurred, leading to acute respiratory failure, treated again with steroid pulse therapy and IVCY. This treatment did not result in improvement of respiratory failure, therefore plasma exchange was attempted, which demonstrated a beneficial effect on the ILD for a short time. This case suggests that IVCY and plasma exchange might be effective therapeutic options for CADM with ILD.

Graves' orbitopathy is an autoimmune disease of the orbit that most frequently occurs with Graves' hyperthyroidism. The occurrence of autoantibodies directed against the TSH receptor (TRAb) is of central importance for the diagnosis and pathogenesis. These autoantibodies are mostly stimulating, and induce uncontrolled hyperthyroidism and tissue remodelling in the orbit and more or less pronounced inflammation. Consequently, patients suffer to a variable extent from periocular swelling, exophthalmos, and fibrosis of the eye muscles and thus restrictive motility impairment with double vision. In recent decades, therapeutic approaches have mainly comprised immunosuppressive treatments and antithyroid drug therapy for hyperthyroidism to inhibit thyroid hormone production. With the recognition that TRAb also activates an important growth factor receptor, IGF1R (insulin-like growth factor 1 receptor), biological agents have been developed. Teprotumumab (an inhibitory IGF1R antibody) has already been approved in the USA and the therapeutic effects are enormous, especially with regard to the reduction of exophthalmos. Side effects are to be considered, especially hyperglycaemia and hearing loss. It is not yet clear whether the autoimmune reaction (development of the TRAb/attraction of immunocompetent cells) is also influenced by anti-IGF1R inhibiting agents. Recurrences after therapy show that the inhibition of antibody development must be included in the therapeutic concept, especially in severe cases., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht./The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This study included 51 patients with muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) from a Japanese multicenter survey to examine clinical features and outcomes. Median onset age was 37 years and female predominance was observed. All patients developed generalized symptoms and almost all (50/51) patients had bulbar symptoms. About half of the patients met the criteria for refractory MG. The refractory group had a lower age of onset, higher severity scores, and higher maximum daily doses of oral prednisolone compared to the nonrefractory group. The outcomes for MuSK-MG patients in Japan are not favorable, indicating the need for more aggressive treatment., Competing Interests: Declaration of Competing Interest AU received honoraria from Alexion Pharmaceuticals and Argenx. SK received Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare of Japan (23FC1009) and honoraria from CSL Behring. TK reported honoraria for lectures from Argenx, Alexon Pharmaceuticals, and UCB Pharma. SS received speakers' fees from Alexion Pharmaceuticals, the Japan Blood Products Organization, Asahi Kasei Medical, and Argenx and participated in advisory board meetings of Alexion Pharmaceuticals and Argenx. MPT reported unrestricted research grants from Japan Blood Products Organization, Astellas Pharma, Mitsubishi Tanabe Pharma, and Pfizer outside the submitted work, served as a paid Consultant for Alexion, Argenx, Sanofi, and UCB Pharma, and received an honorarium for lectures from Argenx, Alexion Pharmaceuticals, and UCB Pharma. MM received speaker honoraria from Argenx, Asahi Kasei Medical, and Alexion Pharmaceutical and participated in advisory board meetings of Alexion Pharmaceutical. YN received speaker honoraria from Argenx, Alexion Pharmaceuticals, Japan Blood Products Organization, and UCB Pharma. KU served as a paid Consultant for UCB Pharma, Janssen Pharma, Horizon Therapeutics (Viela Bio), Chugai Pharma, Hanall BioPharma, Merck, and Mitsubishi Tanabe Pharma and received speaker honoraria from Argenx, Alexion Pharmaceuticals, UCB Pharma, and the Japan Blood Products Organization. Other authors declare no financial or other conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Autoimmune arthritis - such as rheumatoid arthritis - affect a significant proportion of the population, which can cause everyday joint pain, decreased mobility and reduced quality of life. Despite having more and more therapeutic options available, there are still a lot of patients who cannot reach remission or low disease activity by current therapies. This causes an urgent need for the development of new treatment options. The Syk tyrosine kinase plays an essential role in B cell receptor, Fc receptor and integrin signaling. It has been shown that the hematopoietic cell-specific deletion of Syk resulted in a complete protection against autoantibody-induced experimental arthritis. This prompted us to test the effect of entospletinib, a second generation, Syk-selective inhibitor, which has a tolerable safety profile according to hematological clinical trials, in experimental autoimmune arthritis. We found that entospletinib dose-dependently decreased the macroscopic signs of joint inflammation, while it did not affect the health status of the animals. In line with these findings, local neutrophil accumulation and cytokine levels were reduced compared to the vehicle-treated group, while macrophage accumulation and synovial fibroblast numbers were not significantly altered. Meanwhile, entospletinib dose-dependently decreased the cell responses of immune complex- or integrin ligand-activated neutrophils. Overall, we found that selective Syk inhibition by entospletinib reduced the activity of autoantibody-induced experimental arthritis, which seems to be based mainly on the effect of the inhibitor on neutrophil functions. Our data raise the possibility that entospletinib could be a good drug candidate in the treatment of human autoimmune arthritis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that Attila Mócsai was an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Káposztás, Balogh, Mócsai, Kemecsei, Jakus and Németh.)

Objectives: The diagnosis of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and AIH-PBC overlap syndrome (OS) relies on their histologic features and clinical findings. In this study, we aimed to identify specific morphologic features of these diseases and evaluate their clinical correlation., Methods: We included initial biopsies from untreated patients with AIH (n = 14), PBC (n = 10), and OS (n = 7). Histologic features of the portal tract, portal-lobular interface, and hepatic lobule, fibrosis, as well as clinical data including serology, autoantibodies, treatment, and prognosis were reviewed and analyzed., Results: Our results showed that several histologic features differed significantly between AIH and PBC (p < 0.05). Among these features, OS cases were more likely to present with bile duct-centered processes (presence of bile duct damage while absence of inflammation gradient from bile duct to interface, plasma cell cluster and pericentral inflammation) unlike those seen in AIH (p < 0.05), and interface-centered processes (unequivocal interface hepatitis, ductular reaction, and periportal fibrosis) which were not seen in PBC (p < 0.05). We observed a significant correlation between transaminase levels and lobular inflammation, including numbers of lymphocyte, plasma cell and eosinophil. Our study also found that anti-smooth muscle antibody positivity was associated with interface hepatitis (p < 0.01), while antimitochondrial antibody positivity was associated with duct damage (including ductopenia) and granulomas (p < 0.05)., Conclusion: Our results highlight distinctive morphological features between AIH and PBC. The possibility of overlap syndrome should be considered when encountering AIH with bile duct-centered processes or PBC with interface-centered processes in morphology and correlation with autoantibodies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis-associ ated interstitial lung disease (ARS-ILD) has a good prognosis, with few cases progressing to respiratory failure. This study aimed to determine factors predictive of lung function changes in patients with ARS-ILD., Methods: We retrospectively studied 49 patients with ARS-ILD treated at Kurume University Hospital Hospital between 2000 and 2018. We followed 30 patients for more than 2 years after prednisolone (PSL) therapy, with or without calcineurin inhibitors (CNIs), evaluating clinical, physiological, computed tomography, pulmonary func tion, and serological data., Results: After treatment for 24 months, no significant differences were noted between clinical parameters and improvement in forced vital capacity (FVC), %FVC, % carbon monoxide diffusing capacity/alveolar volume (%DLCO), and %DLCO/alveolar volume. Conversely, the annual change of %FVC significantly correlated with the Medical Research Council dyspnea scale grade and %FVC at the first visit and treatment. Furthermore, the annual change of %DLCO/VA significantly correlated with the duration from the first visit to treatment initiation., Conclusion: Compared with PSL monotherapy, combining PSL and CNI showed greater mitigation of %FVC decline. The time from onset of ARS-ILD to the first visit is critical for preventing a decline in lung function, and as such, patients should be monitored carefully.

Background: Anti-LGI1 encephalitis is characterized by a pattern of inflammation that predominantly affects the limbic system It is part of the autoimmune encephalitis that attack neuronal surface antigens. It is characterized by the triad of subacute dementia, faciobrachial dystonic crises, and hyponatremia, presenting an excellent response to immunotherapy. The aim of this article is to describe the clinical evolution and functional outcome at 6 months of two patients with anti-LGI1 encephalitis using clinical cases., Clinical Cases: Case 1: 62-year-old man with 8-week symptoms manifested by changes in mood, disorientation, and focal motor seizures. Case 2 A 72-year-old woman with a 5-month evolution of rapidly progressive dementia, hyponatremia and bitemporal hyperintensities on MRI. In both, due to clinical suspicion, acute dual immunotherapy with steroid and immunoglobulin was given with substantial improvement. Subsequently, the existence of anti-LGI1 antibodies in cerebrospinal fluid was confirmed. Although both patients received a dose of rituximab during their hospitalization, only the patient in the first case continued biannual doses of rituximab. The second patient was not initially considered to continue long-term immunomodulatory treatment and experienced a relapse., Conclusions: These clinical vignettes present the reader with the classic characteristics of this disease. This can facilitate its recognition and timely initiation of treatment, improving the functional prognosis of patients., (Licencia CC 4.0 (BY-NC-ND) © 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

Background: People with neuromyelitis optica spectrum disorder (PwNMOSD) commonly switch between disease modifying therapies, yet the consequence of transitions remains unknown. We aimed to understand if treatment transitions due to medical, non-medical, and tolerability reasons were related to disease progression., Methods: A retrospective study of medical records for PwNMOSD was performed between 2008 and 2022. A comprehensive clinical timeline was created for each person including details related to treatment history and associated clinical and radiological outcomes (i.e., hospital admission, relapses, and MRI advancement). If a transition occurred, the reason for the switch was categorized as being due to medical, non-medical, or tolerability issues. A proportional hazards model was created, and the assumptions were tested based on weighted residuals., Results: The cohort included 164 aquaporin-4 IgG positive NMOSD subjects with 89 (79 female; median disease duration (range) = 10.1 years (y) (1.7-32.8)) people switching therapies at least once (once: 42; twice: 26; three times: 12; four times: 6; 5 or more times: 3). A similar amount of higher efficacy therapies was used by PwNMOSD that switched due to a non-medical/tolerability or a medical-related reason. The results of the recurrent event survival analysis revealed that after an initial transition due to non-medical/tolerability reasons, the risk of a hospital admission, relapse, and MRI advancement decreases by 40.3 % (p = 0.005), 53.1 % (p = 0.002), and 65.9 % (p = 0.005), respectively. However, with each additional discontinuation due to non-medical/tolerability reasons, the risk of hospitalization increased by 25.2 % (p = 0.0003) and risk for MRI advancement increased by 41.9 % (p = 0.03). For transitions due to medical reasons, a significant increased risk of MRI advancement by 32.2 % (p = 0.005) for the first switch was identified with no associated observed risk with each additional discontinuation (p = 0.33). Within the first six months after stopping a medication due to non-medical/tolerability reasons, the rate of starting a new medication was less (p<0.0001) when compared to a discontinuation due to a medical-related event., Conclusions: The risk associated with the time course of treatment transitions for people with NMOSD may assist in transforming the way healthcare providers bridge the gap between therapies and the approach to the timing of a switch. These data highlight additional factors that may be equatable to the efficacy of prescribed treatments in the prevention of acute neurological events., Competing Interests: Declaration of Competing Interest D.T.O. received personal compensation for consulting and advisory services from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, Inc., TG Therapeutics, and research support from Biogen, EMD Serono/Merck, and Novartis. D.T.O. has issued national and international patents along with pending patents related to this current work and other developed technologies and has received royalties for intellectual property licensed by The Board of Regents of The University of Texas System. D.T.O is also the Founder of Revert Health Inc. T.M.M, M.M., K.C., K.W.B., and A.D.S. have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose of Review: The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU)., Recent Findings: Two primary types of autoimmunity, Type I and Type IIb, have emerged as major contributors to CSU, characterized by immunoglobulin E (IgE) and immunoglobulin G (IgG) autoantibodies, respectively. Genetic evidence supports the notion that CSU shares more similarities with other autoimmune diseases rather than atopic diseases. Novel autoallergens such as FcεRI and tissue transglutaminase have been identified, contributed to our understanding of autoimmune mechanisms. Furthermore, the potential overlap between Type I and Type IIb autoimmunity has been recognized. Evaluating the autoimmune status of CSU patients through biomarkers and understanding their clinical implications is vital for effective management. For instance, CSU patients with Type IIb autoimmunity, with or without coexisting Type I autoimmunity, may exhibit resistance to H1-antihistamines and omalizumab treatment but could potentially respond well to cyclosporine or Bruton's tyrosine kinase inhibitors., Summary: Further investigations are needed to explore new autoallergens and autoantibodies in CSU, establishing their connection to the development of autoimmunity. The efficacy of novel drugs targeting different mechanisms should be examined to determine their responses in both autoimmune CSU and nonautoimmunity-related CSU., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This article reviews autoimmune axonal neuropathies, their characteristic clinical features, disease and antibody associations, appropriate ancillary testing, treatment, and prognosis., Latest Developments: In 2021, the American College of Rheumatology and the Vasculitis Foundation released new summary guidelines for the treatment of antineutrophil cytoplasmic autoantibody-associated vasculitides. In addition, novel autoantibodies have been recently identified; they are often paraneoplastic and associated with axonal neuropathies., Essential Points: Recognition of autoimmune axonal neuropathies is important because of the potential for effective treatment to either reverse deficits or slow the progression of disease. It is necessary to properly assess for associations with other systemic disorders (eg, systemic vasculitis, connective tissue disease, neoplasm) so that adequate treatment for both neurologic and non-neurologic aspects of the disease can be initiated., (Copyright © 2023 American Academy of Neurology.)

Background: Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare neuroinflammatory disease characterized by recurrent relapses. The most common signs are myelitis and optic neuritis. It can also present by cerebral or brain stem syndromes. There are still many challenges in its diagnosis and treatment, and long-term follow-up studies are needed to see the disease course over time., Methods: We established an electronic registration system of NMOSD patients starting from October 2015 in Kashani hospital, Isfahan, Iran. Every suspected patient was documented and included in the follow-up system to survey their disease course. Anti-aquaporine 4 (AQP4) antibody checked for all by cell-based assay method. All information such as demographic and clinical data and laboratory and MRI findings were documented. Participants were followed up for any relapses, new paraclinical tests and drug changes. This study is based on the definite NMOSD cases (according to the 2015 criteria) characteristics and clinical course during 7 years of registration., Results: The study included 173 NMOSD cases and 56 ones were seropositive for AQP4 Ab. Their mean age was 40.02±11.11 years (45.78 in the seropositive group). The mean age at disease onset was about 30.16 years. The mean time of follow-up by our registration system is 55.84 ± 18.94 months (54.82 months in seropositive ones). The annual relapse rate is estimated as 0.47±0.36. Long extended transvers myelitis (LETM) was present in the baseline MRI of 77 patients (44.5%), while 32 of them did not show any related clinical symptoms. 124 patients revealed an abnormality in the first brain MRI. 27 individuals suffer hypothyroidism as the most common comorbid disease. The disease seems to be more prevalent in the west and southwest areas of Isfahan province., Conclusion: The mean age of onset is higher than Multiple Sclerosis (MS) patients, but there are notable pediatric cases too. It should also be noticed that cervical LETM can be asymptomatic at first. Brain MRI abnormalities are frequently observed. The disease is more prevalent in the geographical areas where showing high MS prevalence., Competing Interests: Declaration of Competing Interest The corresponding author, on behalf of the others, declares no conflict of interest. All aspects of human research are considered by the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Goodpasture's disease and anti-glomerular basement membrane nephritis (anti-GBM nephritis) are rare autoimmune small vessel vasculitis predominantly affecting young men. Goodpasture's disease plays an important part in differential diagnosis of pulmonary - renal syndrome. The evidence of circulating autoantibodies, a typical histological appearance of the kidney biopsy with finding of the crescent glomerulonephritis and clinical presentation of nephritic syndrome play an important role in diagnosis. Our case report describes a case of a young male with anti-GBM nephritis that presents as rapidly progressive glomerulonephritis (RPGN) with progression to dialysis-dependent renal failure. The atypical sign of the case was development of nephrotic syndrome with volume-dependent hypertension. The case was complicated by heparin-induced thrombocytopenia. During combined immunosuppressive therapy with plasmapheresis, the condition of the patient has stabilized. However, renal function did not recover. This previously fatal disease has nowadays a very good survival rate because of immunosuppresion therapy, plasmapheresis and hemodialysis.

Muscle-specific tyrosine kinase myasthenia gravis (MuSK MG) is an autoimmune disease that causes life-threatening muscle weakness due to anti-MuSK autoantibodies that disrupt neuromuscular junction signaling. To avoid chronic immunosuppression from current therapies, we engineered T cells to express a MuSK chimeric autoantibody receptor with CD137-CD3ζ signaling domains (MuSK-CAART) for precision targeting of B cells expressing anti-MuSK autoantibodies. MuSK-CAART demonstrated similar efficacy as anti-CD19 chimeric antigen receptor T cells for depletion of anti-MuSK B cells and retained cytolytic activity in the presence of soluble anti-MuSK antibodies. In an experimental autoimmune MG mouse model, MuSK-CAART reduced anti-MuSK IgG without decreasing B cells or total IgG levels, reflecting MuSK-specific B cell depletion. Specific off-target interactions of MuSK-CAART were not identified in vivo, in primary human cell screens or by high-throughput human membrane proteome array. These data contributed to an investigational new drug application and phase 1 clinical study design for MuSK-CAART for the treatment of MuSK autoantibody-positive MG., (© 2023. The Author(s).)

Background: Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear., Methods: The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively., Results: Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group., Conclusion: Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Zhang et al.)

A 58-year-old female presented to a lifestyle medicine clinic in 2019 with a one-year history of pemphigus vulgaris (PV) and having itching, burning sensations, and bulla formation all over her body. She further had a recent diagnosis of type 2 diabetes mellitus and also complained of malaise, indigestion, and anxiety due to her skin condition. She was on methyl prednisolone, metformin, and other herbal supplements for 1 year to control her PV and diabetes. Laboratory investigations revealed the presence of autoantibodies Desmoglein 1 and 3 with titers of 3.26 and 3.5, respectively.The patient underwent a yoga & naturopathy-based lifestyle modification program for a period of 53 days in 2019, followed by 10 days in 2020 and 15 days in 2021, and subsequent follow-up measures. This included hydrotherapy, yoga, a vegetarian diet, herbal preparations, massage, etc. By the end of 2020, the patient was tapered from all medications, and there was complete remission from PV. Given the multidimensional impact of PV, a holistic, patient-centered lifestyle approach as described in this case may be beneficial in managing PV. Further research is warranted in this area., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Autoimmune Hepatitis (AIH) is an immune-mediated liver disease of unknown origin. Its clinical presentation is heterogeneous and ranges from asymptomatic courses over several years to acute forms with acute liver failure. Accordingly, the diagnosis is only made at the stage of cirrhosis in about one third of affected individuals. Early diagnosis and a consistent, adequate, individualized, immunosuppressive therapy are crucial for the prognosis, which is excellent when treated properly. AIH is rare in the general population and can be easily overlooked due to its variable clinical picture and sometimes difficult diagnosis. AIH should be considered as a differential diagnosis in any unclear acute or chronic hepatopathy. The therapy initially consists of remission induction and subsequently maintenance therapy with (often lifelong) immunosuppressants., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. By contrast, some immune-related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. This study investigated plasma cytokine, chemokine, and anti-CD74 autoantibody levels in patients with renal cell carcinoma (RCC) and analyzed their association with irAEs. In a discovery cohort of 13 patients, plasma levels of chemokine (C-X-C motif) ligand (CXCL) 1, IL-17A, IL-1β, IL-6, IL-8, CXCL10, MCP-1, and TNFα were measured at baseline and post-dose 1. Only CXCL10, at post-dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (P = 0.0413). Plasma CXCL10 levels were then measured at baseline and post-dose 1 in an extended cohort of 43 patients with RCC who received ICI-based treatment. Higher plasma CXCL10 levels both at baseline and post-dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (P = 0.0246 and 0.0137, respectively). Plasma CXCL13 levels, which we measured in a previous study, were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post-dose 1 (P = 0.0037 and 0.052, respectively). No significant association between plasma anti-CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. In conclusion, plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on-treatment biomarker for irAEs., (© 2023 The Societies and John Wiley & Sons Australia, Ltd.)

Autoimmune encephalitis (AE) is an important cause of encephalitis in humans and occurs at a similar rate to infectious encephalitis. It is frequently associated with antibodies against the extracellular domain of neuronal proteins. Among human AE, that with antibodies against leucine-rich glioma-inactivated 1 (LGI1) is one of the most prevalent forms, and was recently described in cats with limbic encephalitis (LE). In this study, we describe a large cohort (n = 32) of cats with AE, tested positive for voltage gated potassium channel (VGKC)-antibodies, of which 26 (81%) harboured LGI1-antibodies. We delineate their clinical and paraclinical features as well as long-term outcomes up to 5 years. Similar to human cases, most cats with LGI1-antibodies had a history of focal seizures (83%), clustering in the majority (88%), with interictal behavioural changes (73%). Among feline AE patients, there was no seizure type or other clinical characteristic that could distinguish LGI1-antibody positive from negative cats, unlike the pathognomic faciobrachial dystonic seizures seen in humans. Although six cats were euthanased in the first year for epilepsy-associated reasons, those attaining at least 1-year survival had good seizure control and quality of life with appropriate veterinary care and medication. Acute-phase immunotherapy (prednisolone) was given to the most severely unwell cases and its effect is retrospectively evaluated in 10 cats. Our data show LGI1-antibodies are an important cause of feline encephalitis, sharing many features with human AE. Further research should examine optimal therapeutic management strategies and the cause of LE in seronegative cats, building on paradigms established in the counterpart human disease., (Copyright © 2023. Published by Elsevier Ltd.)

Development of novel therapeutic antibodies that not only kill tumor cells but modulate the adaptive immune response has the potential to produce long term anticancer immunity and a durable clinical response. We previously reported the discovery of anti-complement factor H (CFH) autoantibodies in patients with lung cancer that were associated with early-stage disease and exceptional outcomes. The human mAb GT103, produced from a single CFH autoantibody-expressing B cell of a patient with lung cancer, recognizes a conformationally distinct epitope on tumor cells, kills tumor cells, and inhibits tumor growth in animal studies. Recent experiments have shown that GT103 restructures the tumor microenvironment and initiates a robust antitumoral adaptive immune response. The current study further elucidates several mechanisms by which GT103 kills tumor cells and drives the immune program. Here we show GT103 has specificity for tumor cells without binding to native soluble CFH or normal tissues. GT103 causes complement C3 split product deposition on tumor cells in vitro and in vivo, triggers antibody-dependent cellular phagocytosis, and increases translocation of the danger-associated molecular pattern molecule calreticulin to the plasma membrane. We also demonstrate that GT103 causes B-cell activation in vitro and in vivo, and that GT103 antitumor activity in vivo is B-cell dependent. The complex mechanism of GT103, a tumor-specific antibody that kills tumor cells and stimulates an immune response, supports further development of this human-derived antibody as a novel therapeutic option for patients with lung cancer., (©2023 American Association for Cancer Research.)

Systemic sclerosis (SSc) is a rare and chronic autoimmune disease characterized by a pathogenic triad of immune dysregulation, vasculopathy, and progressive fibrosis. Clinical tools commonly used to assess patients, including the modified Rodnan skin score, difference between limited or diffuse forms of skin involvement, presence of lung, heart or kidney involvement, or of various autoantibodies, are important prognostic factors, but still fail to reflect the large heterogeneity of the disease. SSc treatment options are diverse, ranging from conventional drugs to autologous hematopoietic stem cell transplantation, and predicting response is challenging. Genome-wide technologies, such as high throughput microarray analyses and RNA sequencing, allow accurate, unbiased, and broad assessment of alterations in expression levels of multiple genes. In recent years, many studies have shown robust changes in the gene expression profiles of SSc patients compared to healthy controls, mainly in skin tissues and peripheral blood cells. The objective analysis of molecular patterns in SSc is a powerful tool that can further classify SSc patients with similar clinical phenotypes and help predict response to therapy. In this review, we describe the journey from the first discovery of differentially expressed genes to the identification of enriched pathways and intrinsic subsets identified in SSc, using machine learning algorithms. Finally, we discuss the use of these new tools to predict the efficacy of various treatments, including stem cell transplantation. We suggest that the use of RNA gene expression-based classifications according to molecular subsets may bring us one step closer to precision medicine in Systemic Sclerosis., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCV/HIV co-infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co-infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIV/HCV co-infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti-thyroglobulin Ab, anti-thyroid peroxidase Ab, ANCA, ASMA, anti-LKM, anti-DNA, AMA, ANA, T CD4+ and CD8+ cell count, and CD4/CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals: 51.9% with a F0-F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4; ferritin, anti-thyroglobulin Ab, and C4 fraction at EOT; total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p < .001). T CD4+ cell slightly increased at SVR12, but with an increase also in CD8+ resulting in stable CD4/CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p = .099): they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4/CD8 ratio over a follow up of 12 weeks., (© 2023 John Wiley & Sons Ltd.)

Introduction: Immune checkpoint inhibitors (ICIs) are now standard of care in many cancers. They can generate immune-related adverse events (irAEs), but no biomarkers are available to identify patients who are more likely to develop irAEs. We assess the association between pre-existing autoantibodies and occurrence of irAEs., Patients and Methods: We prospectively collected data from consecutive patients receiving ICIs for advanced cancers, in a single center between May 2015 and July 2021. Autoantibodies testing was performed before ICIs initiation including AntiNeutrophil Cytoplasmic Antibodies, Antinuclear Antibodies, Rheumatoid Factor anti-Thyroid Peroxidase and anti-Thyroglobulin. We analyzed the associations of pre-existing autoantibodies with onset, severity, time to irAEs and with survival outcomes., Results: Of the 221 patients included, most had renal cell carcinoma (n = 99; 45%) or lung carcinoma (n = 90; 41%). Grade ≥2 irAEs were more frequent among patients with pre-existing autoantibodies: 64 (50%) vs. 20 (22%) patients (Odds-Ratio= 3.5 [95% CI=1.8-6.8]; p < 0.001) in the positive vs negative group, respectively. irAEs occurred earlier in the positive group with a median time interval between ICI initiation and irAE of 13 weeks (IQR = 8.8-21.6) vs. 28.5 weeks (IQR=10.6-55.1) in the negative group (p = 0.01). Twelve patients (9.4%) experienced multiple (≥2) irAEs in the positive group vs. 2 (2%) in the negative group (OR = 4.5 [95% CI: 0.98-36], p = 0.04). After a median follow-up of 25 months, median PFS and OS were significantly longer among patients experiencing irAE (p = 0.00034 and p = 0.016, respectively)., Conclusion: The presence of pre-existing autoantibodies is significantly associated with the occurrence of grade ≥2 irAEs, with earlier and multiple irAEs in patients treated with ICIs., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Side effects of immune checkpoint inhibitors (ICIs), called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. We aimed to understand the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs., Patients and Methods: Patients without pre-existing autoimmune disease (pAID) who had cancer treated with ICI(s) treatment from 1/1/2011 to 12/21/2020 and a rhAb checked were retrospectively identified. Logistic regression assessed associations between autoantibodies and irAEs, cancer outcome, and survival. Specificity, sensitivity, and positive/negative predictive values (PPV, NPV) were estimated for key rhAbs and ICI-arthritis. Kaplan-Meier analyzed objective response rate (ORR) and overall survival (OS)., Results: A total of 2662 patients were treated with≥1 ICIs. One hundred and thirty-five without pAID had ≥ 1 rhAb tested. Of which 70/135(52%) were female; median age at cancer diagnosis was 62 years with most common cancers: melanoma (23%) or non-small cell lung cancer (21%), 96/135 (75%) were anti-PD1/PDL1 treated. Eighty had a rhAb ordered before ICI, 96 after ICI, and 12 before and after. Eighty-two (61%) experienced an irAE, 33 (24%) with rheumatic-irAE. Pre-ICI RF showed significant association with rheumatic-irAEs (OR = 25, 95% CI, 1.52-410.86, P = .024). Pre- and post-ICI RF yielded high specificity for ICI-arthritis (93% and 78%), as did pre- and post-ICI CCP (100% and 91%). Pre-ICI RF carried 93% NPV and pre-ICI CCP had 89% PPV for ICI-arthritis. No variables were significantly correlated with ORR. Any-type irAE, rheumatic-irAE and ICI-arthritis were all associated with better OS (P = .000, P = .028, P = .019)., Conclusions: Pre-ICI RF was associated with higher odds of rheumatic-irAEs. IrAEs had better OS; therefore, clinical contextualization for rhAbs is critical to prevent unnecessary withholding of lifesaving ICI for fear of irAEs., (© The Author(s) 2023. Published by Oxford University Press.)

Intravenous efgartigimod alfa (also known as efgartigimod alfa-fcab in the USA; Vyvgart ® ) is the first neonatal Fc receptor antagonist approved in several countries worldwide, including the USA and EU for the treatment of generalised myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of gMG regardless of antibody status. In the double-blind, placebo-controlled phase 3 ADAPT trial in patients with gMG, efgartigimod alfa significantly and rapidly reduced disease burden and improved muscle strength and quality of life compared with placebo. The clinical benefits of efgartigimod alfa were durable and reproducible. Furthermore, in an interim analysis of the ongoing open-label phase 3 ADAPT+ extension trial, efgartigimod alfa provided consistent clinically meaningful improvements in patients with gMG. Efgartigimod alfa was generally well tolerated, with most adverse events being mild to moderate in severity., (© 2023. Springer Nature.)

Satralizumab (Enspryng ® ) is a monoclonal antibody that blocks the interleukin-6 (IL-6) receptor and is approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in patients who are aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive. Patients with NMOSD are at risk of recurrent autoimmune attacks that primarily target the optic nerves and spinal cord but may also target other regions of the central nervous system; these attacks can lead to life-long disability. In the randomized, placebo-controlled phase III SAkuraSky and SAkuraStar trials, subcutaneous satralizumab as an add-on to immunosuppressive therapy or as a monotherapy, respectively, significantly reduced the risk of relapse compared with placebo in patients who were AQP4-IgG seropositive with NMOSD. Satralizumab was well tolerated; the most common adverse events were infection, headache, arthralgia, decreased white blood cell count, hyperlipidaemia and injection-related reactions. In the EU, satralizumab is the first IL-6 receptor blocker to be approved for treatment of AQP4-IgG-seropositive patients with NMOSD, has the potential advantage of subcutaneous administration, and is the only targeted treatment approved for adolescent patients with this disorder. Thus, satralizumab is a valuable treatment option for patients with NMOSD., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Dermatomyositis (DM) is an autoimmune disorder, which belongs to a group of rare autoimmune dermatoses characterized by different skin features and variable muscle involvement. We recognize four main variants of DM: classic DM, clinically amyopathic DM, paraneoplastic DM, and juvenile DM. Clinically, patients show several skin features, but heliotrope rash, and violaceous papules located at the interphalangeal or metacarpophalangeal joints (Gottron's papules) are the most frequently observed. Together with skin features, patients show muscle involvement, most commonly with symmetrical weakness of the proximal muscles. DM belongs to the facultative paraneoplastic dermatoses and a wide range of solid or hematologic malignancies can be detected in DM patients. Serologically, a wide range of autoantibodies can be detected in patients with DM. Indeed, distinct serotypes can be related to specific phenotypes with specific clinical features, carrying a different risk for systemic involvement and for malignancies. Systemic corticosteroids are still considered the first-line approach, but several steroid-sparing agents, such as methotrexate, azathioprine or mycophenolate mofetil, have been reported as effective in treating DM. Furthermore, new class of drugs, such as monoclonal antibodies, purified immunoglobulins or Janus kinase inhibitors are becoming more relevant in the clinical practice or are currently under investigation. In this work, we aim to offer a clinical overview of the diagnostic workout, the characteristics of DM variants, the role of autoantibodies in DM, and the management of this life-threatening systemic disorder.

Objective: Statin-associated autoimmune myopathy (SAAM) is a rare adverse event characterized by progressive muscle symptoms despite discontinuation, requiring immunosuppressive therapy for remission. The objective of this review was to characterize SAAM, for timely detection, while examining the literature for effective treatment considerations. Methods: PubMed search was conducted from 2010 to 2020 was for relevant case series and studies of at least 8 patients displaying muscle discomfort or weakness, anti-HMGCR antibodies, exposure to statins, and biopsies consistent with SAAM. Results: Three case series and 3 case cohort studies identified 199 patients with SAAM. Exhibiting a mean age of 63.74 years, patients were more likely Caucasian (81%) and female (1.2X), and required a mean duration of 4.75 years before symptomatic. The presentation involved proximal muscle weakness (94%), myalgias (37%) and dysphagia (23%), accompanied by a mean creatinine kinase of 6383 IU/L. Most patients (57%) required 2 or more immunosuppressive (IMS) agents to achieve 62% remission. After 2 years of treatment, 15% of patients without remission reported symptomatic improvement, while another 12% were refractory to treatment. Conclusion: Delayed onset of SAAM greater than 4 years from statin initiation may create a low index of suspicion. However, progression of symptoms beyond 2 months from statin discontinuation and positive anti-HMGCR antibodies requires immunosuppressive agents. Data and expert opinion support use of at least two IMS medications upon diagnosis for a minimum of 2 years. Therapy success depends on timely recognition and initiation of IMS combinations to achieve earlier remission and symptomatic improvement.

Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

Purpose: This study describes the therapeutic strategies in NMOSD and MOGAD adopted by neurologists to treat both conditions in Latin America (LATAM) with main focus on rituximab (RTX) and the disease outcome., Methods: retrospective study in a cohort of NMOSD and MOGAD patients followed in specialized MS/NMOSD centers from eight countries and 14 LATAM reference centers. Demographics and clinical characteristics were collected. RTX strategies on naïve (for rituximab) patients were summarized as follows: scheme A: two 1000 mg infusions 15 days apart and repeated every 6 months; scheme B: four 375 mg/m2 infusions every week for 4 weeks and repeated every 6 months; scheme C: one 1000 mg infusions and repeated every 6 months; scheme D: other scheme used. Relapse rate and adverse events during follow-up were analyzed considering the different RTX schemes. Poisson and logistic regression analysis were used to assess baseline aspects and disease activity during follow-up., Results: A total of 217 patients were included. 197 were NMOSD patients (164, 83.2% AQP4-IgG seropositive and 16.7% seronegative) and 20 were MOGAD patients. The most frequent long-term treatment was RTX in both groups (48.2% and 65% for NMOSD and MOGAD patients, respectively). The most common RTX regimen used in 79 (83.1%) patients was two 1000 mg infusions 15 days apart and repeat every 6 months. Relapses under RTX treatment were observed in 21 (22.1%) patients. Relapses after RTX treatment were associated with higher EDSS (OR 1.75, 95%CI 1.44-2.34, p = 0.03) and higher ARR pre-RTX (OR = 2.17, 95% CI 1.72-3.12, p = 0.002) but not with RTX regimen (OR = 1.10, 95% CI 0.89-1.21, p = 0.60)., Conclusion: the most strategy used in LATAM was RTX with two 1000 mg infusions 15 days apart. Relapses during follow up were not associated with RTX regimen used., Competing Interests: Declaration of Competing Interest JIR has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis. TA has received consulting fees, lecture honoraria and Travel Support from Biogen, Merck, Roche and Teva. PAL has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis and Roche. JF has received consulting fees from Biogen, Novartis and Genzyme, as a lecturer from Merck Serono, Novartis and Biogen, and collaboration for attendance to national and international congresses from Biogen, Novartis, Merck Serono, Bayer and Gador. FG has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis, Bayer. CN has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Stendhal, Roche, Biogen, Genzyme, Merck, Novartis, Biopas. LP has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis. EC has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis. ECC has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Bayer, Biogen, Ipsen, Merck, Novartis, Roche, Sanofi, Teva. The rest of the authors declares not conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Autoimmune hepatitis (AIH) is a rare autoimmune disease of the liver with many open questions as regards its etiopathogenesis, natural history and clinical management. The classical picture of AIH is chronic hepatitis with fluctuating elevation of serum transaminases and Immunoglobulin G levels, the presence of circulating autoantibodies and typical histological features. However, atypical presentations do occur and are not well captured by current diagnostic scores, with important consequences in terms of missed diagnoses and delayed treatments. AIH is treated with corticosteroids and immunosuppressive drugs but up to 40% of patients do not achieve full biochemical response and are at risk of progressing to cirrhosis and liver failure. Moreover, standard therapies are associated by significant side-effects which may impair the quality of life of patients living with AIH. However, advances in the understanding of the underlying immunology of AIH is raising the prospect of novel therapies and optimization of existing therapeutic approaches to reduce side-effect burdens and potentially restore immunological tolerance. In this review we outlined the clinical characteristics, etiopathogenesis and management of AIH and current challenges in the diagnosis and management of AIH and provided evidence underlying the evolution of diagnostic and clinical management protocols.

Systemic sclerosis (formerly scleroderma) is a relatively rare autoimmune connective tissue disease which symmetrically affects the skin and affects the internal organs. There are two types: limited cutaneous and diffuse cutaneous. Each type is categorized by different clinical, systemic, and serologic findings. Autoantibodies can be used to predict phenotype and internal organ involvement. Systemic sclerosis can affect the lungs, gastrointestinal system, kidneys, and heart. Pulmonary and cardiac disease are the leading causes of death, so screening for these conditions is important. Early management of systemic sclerosis is paramount to prevent progression. Numerous therapeutic interventions for systemic sclerosis exist, but there is no cure. The goal of therapy is to improve quality of life by minimizing specific organ-threatening involvement and life-threatening disease., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

To estimate the risk of systemic lupus erythematosus (SLE) flares based on the autoantibody positivity at the time of SLE diagnosis. This retrospective cohort study included 228 patients with newly diagnosed SLE. Clinical characteristics including autoantibody positivity at the time of diagnosis of SLE were reviewed. Flares were defined as a new British Isles Lupus Assessment Group (BILAG) A score or BILAG B score for at least one organ system. Multivariable Cox regression analyses were performed to estimate the risk of flares according to autoantibody positivity. Anti-dsDNA, anti-Sm, anti-U1RNP, anti-Ro, and anti-La antibodies (Abs) were positive in 50.0%, 30.7%, 42.5%, 54.8%, and 22.4% of the patients, respectively. The incidence rate of flares was 28.2/100 person-years. Multivariable Cox regression analysis, adjusted for potential confounders, revealed that anti-dsDNA Ab positivity (adjusted hazard ratio [HR]: 1.46, p = 0.037) and anti-Sm Ab positivity (adjusted HR: 1.81, p = 0.004) at the time of diagnosis of SLE were associated with higher risk of flares. To better delineate the flare risk, patients were categorized as double-negative, single-positive, double-positive for anti-dsDNA and anti-Sm Abs. Compared with double-negativity, double-positivity (adjusted HR: 3.34, p < 0.001) was associated with higher risk of flares, while anti-dsDNA Ab single-positivity (adjusted HR: 1.11, p = 0.620) or anti-Sm Ab single-positivity (adjusted HR: 1.32, p = 0.270) was not associated with higher risk of flares. Patients who are double-positive for anti-dsDNA and anti-Sm Abs at the time of the diagnosis of SLE are at higher risk of flares and may benefit from stringent monitoring and early preventive treatment., (© 2023. The Author(s).)

Systemic sclerosis (SSc) is a complex, immune-mediated rheumatic disease characterised by excessive extracellular matrix deposition in the skin and internal organs. B cell infiltration into lesional sites such as the alveolar interstitium and small blood vessels, alongside the production of defined clinically relevant autoantibodies indicates that B cells play a fundamental role in the pathogenesis and development of SSc. This is supported by B cell and fibroblast coculture experiments revealing that B cells directly enhance collagen and extracellular matrix synthesis in fibroblasts. In addition, B cells from SSc patients produce large amounts of profibrotic cytokines such as IL-6 and TGF-β, which interact with other immune and endothelial cells, promoting the profibrotic loop. Furthermore, total B cell counts are increased in SSc patients compared with healthy donors and specific differences can be found in the content of naïve, memory, transitional and regulatory B cell compartments. B cells from SSc patients also show differential expression of activation markers such as CD19 which may shape interactions with other immune mediators such as T follicular helper cells and dendritic cells. The key role of B cells in SSc is further supported by the therapeutic benefit of B cell depletion with rituximab in some patients. It is notable also that B cell signaling is impaired in SSc patients, and this could underpin the failure to induce tolerance in B cells as has been shown in murine models of scleroderma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Beesley, Goldman, Taher, Denton, Abraham, Mageed and Ong.)

The use of immune checkpoint inhibitors (ICIs) has evolved rapidly with unprecedented treatment benefits being obtained for cancer patients, including improved patient survival. However, over half of the patients experience immune related adverse events (irAEs) or toxicities, which can be fatal, affect the quality of life of patients and potentially cause treatment interruption or cessation. Complications from these toxicities can also cause long term irreversible organ damage and other chronic health conditions. Toxicities can occur in various organ systems, with common observations in the skin, rheumatologic, gastrointestinal, hepatic, endocrine system and the lungs. These are not only challenging to manage but also difficult to detect during the early stages of treatment. Currently, no biomarker exists to predict which patients are likely to develop toxicities from ICI therapy and efforts to identify robust biomarkers are ongoing. B cells and antibodies against autologous antigens (autoantibodies) have shown promise and are emerging as markers to predict the development of irAEs in cancer patients. In this review, we discuss the interplay between ICIs and toxicities in cancer patients, insights into the underlying mechanisms of irAEs, and the involvement of the humoral immune response, particularly by B cells and autoantibodies in irAE development. We also provide an appraisal of the progress, key empirical results and advances in B cell and autoantibody research as biomarkers for predicting irAEs. We conclude the review by outlining the challenges and steps required for their potential clinical application in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Taylor, Gandhi, Gray and Zaenker.)

Dermatomyositis positive anti-melanoma differentiation-associated gene 5 (anti-MDA5 DM) is a rare disease that represents less than 2%. The prevalence of anti-MDA5 DM ranges from 7 to 60%, with higher prevalence in Asian (11-60%) and women. The clinical picture may be variable and is accompanied by the typical features of dermatomyositis, such as periorbital heliotrope (blue-purple) rash with edema, erythematous rash on the face, or the anterior chest (in a V-sign), and back and shoulders (in a shawl sign), violaceous papules or plaques located on the dorsal part of the metacarpophalangeal or interphalangeal joints, which are pathognomonic by definition; yet, one of the most striking signs is the painful ulceration skin that is found in 82% of cases, which is deep and in punching holes or showing hyperkeratotic crusts. For diagnosis is necessary the typical DM rashes (Gottron's papules or Gottron's sign and heliotrope rash), along with either an "interface dermatitis" skin pathology or evidence of myositis or a MSA (myositis-specific autoantibodies). Immunoprecipitation is the gold standard method to detect MSA. Combinations of glucocorticoids and immunosuppressants are used for treatment; besides, it is necessary the detection of rapidly progressive interstitial disease (RP-ILD) with a high-resolution CT because of its high association with fatal prognosis., (© 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

Elevated lipid panels are associated with an increased risk of cardiovascular disease. Management of heart disease with lipid lowering agents play a vital role in medicine. Statins are one group of medications that are widely utilized in the medical field to decrease the risk of atherosclerotic disease. Statins work by inhibiting the hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Although statins are one of the most effective drugs for secondary and primary prevention of heart disease, they are not without risks and side effects such as hepatotoxicity and myopathy. We present a case of a male patient who developed progressively worsening muscle weakness and elevated muscle enzyme markers upon initiation of a statin. His symptoms persisted despite a trial of an alternative statin and subsequent discontinuation of all statin medications. A multitude of possible etiologies were considered and ranged from infectious, autoimmune, cancerous, to congenital in nature. Environmental factors, such as exposure to medications or toxins, were also considered as one of the possible precipitating factors. The association between his statin consumption and muscle weakness were not easily apparent at first. He required further workup including physical examination, electromyography, panel of myositis antibodies, and muscle biopsy. After clinical suspicion and elevated antibodies to HMGCR beyond the normal limit, he was discovered to have statin-associated autoimmune myopathy. The patient improved with the treatment of immunosuppressive agent's prednisone and methotrexate.

Objective: This study aimed to explore the prevalence and associated factors of thyroid dysfunction among cancer patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs)., Methodology: A cross-sectional study was done in patients who received TKIs at Rajavithi Hospital in 2019. For patients treated with ICI, a retrospective chart review for patients seen in 2018 to 2019 was conducted. If there were abnormal thyroid function tests (TFT), thyroid autoantibodies were tested., Results: There were 144 patients on TKIs with a mean age of 56.0 years. Thyroid dysfunction was found in 14.6% of patients and most had subclinical hypothyroidism (n = 16, 11.1%). Imatinib (n = 11, 10.8%) and sunitinib (n = 4, 100%) were the 2 most common TKIs given to patients with thyroid dysfunction. Thyroid dysfunction was associated with male sex, chronic kidney disease and hepatitis B virus infection but not with previous thyroid disease and presence of thyroid autoantibodies.There were 18 patients who received ICIs. The mean age was 63.3 years. Twelve patients (66.7%) used programmed cell death protein-1 antibody (anti-PD1), mainly nivolumab. Thyroid dysfunction was found in 50%, which occurred at a median duration of 46 days. Most patients had overt hypothyroidism and 55.6% needed levothyroxine replacement., Conclusion: Thyroid dysfunctions from TKIs were mostly asymptomatic and mild in severity. Some types of TKIs might be associated with thyroid dysfunction. On the other hand, thyroid dysfunction from ICIs usually occurs within 6 months and requires levothyroxine replacement., Competing Interests: The authors declared no conflict of interest., (© 2023 Journal of the ASEAN Federation of Endocrine Societies.)

Postinfectious neuroinflammation has been implicated in multiple models of acute-onset obsessive-compulsive disorder including Sydenham chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

NEUROMYELITIS OPTICA. Neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD) includes different inflammatory conditions of the central nervous system distinct from multiple sclerosis. It is characterized by the association of typical clinical manifestations, such as optic neuritis, extensive transverse myelitis, involvement of the area postrema, and by the presence of anti-aquaporin 4 antibodies. It evolves with relapses. These can be lethal and justify emergency treatment with the administration of high dose of intravenous corticosteroids possibly associated with plasma exchange sessions. A disease modifying treatment is then started to prevent the occurrence of a new relapse., Competing Interests: T. Roux déclare des interventions ponctuelles pour Alexion, Biogen, BMS-Celgene, Merck, Novartis, Sanofi Genzyme et avoir été pris en charge à l’occasion de déplacement pour congrès par Biogen, Merck, Teva. E. Maillart et C. Papeix déclarent des interventions ponctuelles pour Biogen, Merck, Novartis, Roche, Teva, Alexion, Sanofi, BMS et avoir été pris en charge à l’occasion de déplacement pour congrès par Biogen, Merck, Novartis, Roche, Teva, Alexion, Sanofi.

Purpose of Review: This article highlights the clinical and diagnostic features of inclusion body myositis (IBM) and provides recent insights into the pathomechanisms and therapeutic strategies of the disease., Recent Findings: IBM is an often-misdiagnosed myopathy subtype. Due to the insidious onset and slow progression of muscle weakness, it can often be dismissed as a sign of aging as it commonly presents in older adults. While challenging to recognize upon initial clinical evaluation, the recent recognition of specialized stains highlighting features seen on muscle pathology, the use of diagnostic tools such as the anti-cytosolic 5'-nucleotidase 1A antibody biomarker, and the ability of muscle imaging to detect patterns of preferential muscle involvement seen in IBM has allowed for earlier diagnosis of the disease than was previously possible. While the pathogenesis of IBM has historically been poorly understood, several ongoing studies point toward mechanisms of autophagy and highly differentiated cytotoxic T cells that are postulated to be pathogenic in IBM., Summary: Overall advancements in our understanding of IBM have resulted in improvements in the management of the disease and are the foundation of several strategies for current and upcoming novel therapeutic drug trials in IBM., (Copyright © 2022 American Academy of Neurology.)

Background: The goal of this study was to examine the temporal relationship of eye pain to visual loss and investigate whether timing of steroid treatment affects the rate and extent of visual recovery in optic neuritis (ON) from MOG-IgG associated disease (MOGAD) in a large cohort of MOGAD patients with ON., Methods: This is a multicenter, retrospective cohort study of consecutive MOGAD patients with ON attacks seen from 2017 to 2021 fulfilling the following criteria: (1) clinical history of ON; (2) MOG-IgG seropositivity. ON attacks were evaluated for presence/duration of eye pain, nadir of vision loss, time to intravenous methylprednisolone (IVMP) treatment, time to recovery, and final visual outcomes., Results: There were 107 patients with 140 attacks treated with IVMP and details on timing of treatment and outcomes. Eye pain was present in 125/140 (89%) attacks with pain onset a median of 3 days (range, 0 to 20) prior to vision loss. Among 46 ON attacks treated with IVMP within 2 days of onset of vision loss, median time to recovery was 4 days (range, 0 to 103) compared to 15 days (range, 0 to 365) in 94 ON attacks treated after 2 days (p = 0.004). Those treated within 2 days had less severe VA loss at time of treatment (median LogMAR VA 0.48, range, 0.1 to 3) compared to those treated after 2 days (median LogMAR VA 1.7, range, 0 to 3; p < 0.001), and were more likely to have a VA outcome of 20/40 or better (98% vs 83%, p = 0.01). After adjustment for the initial VA at time of treatment, the differences in final VA were no longer significantly different (p = 0.14). In addition, some patients were documented to recover without steroid treatment., Conclusion: This study suggests that pain precedes vision loss in the majority of ON attacks and early steroids may lead to better outcomes in MOG-IgG ON, but some patients can recover without steroid treatment. Prospective randomized clinical trials are required to confirm these findings., Competing Interests: Declaration of Competing Interests None., (Copyright © 2022. Published by Elsevier B.V.)

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder affecting the central nervous system that is associated with significant morbidity and mortality. Early diagnosis and treatment are essential to minimize long-term disability. Recent advances in the understanding of the pathophysiology of NMOSD have led to multiple new therapies, but significant care and knowledge gaps persist. OBJECTIVES: To summarize current knowledge about the burden of disease and diagnosis and treatment of NMOSD in order to support managed care professionals and health care providers in making collaborative, evidence-based decisions to optimize outcomes among patients with NMOSD. In addition, this review also presents findings of a patient survey that provides insight into real-world experiences of those living with NMOSD. SUMMARY: Diagnosis of NMOSD is based on detection of immunoglobulin G antibodies to the water channel protein aquaporin-4 (AQP4-IgG) in the context of compatible clinical and magnetic resonance imaging features. Patients who are AQP4-IgG seronegative and/or who are positive for myelin oligodendrocyte glycoprotein antibodies may also satisfy criteria for NMOSD. The rarity of the condition combined with the significant overlap in clinical features with other autoimmune diseases affecting the central nervous system, most notably multiple sclerosis, can delay accurate diagnosis, which in turn can delay appropriate treatment, leading to the accumulation of long-term disability. Accumulating disability associated with NMOSD has a substantial negative impact on quality of life. The disease typically evolves as relapsing (ie, repeated) acute attacks. Treatment consists of management of acute attacks, prevention of subsequent attacks, and management of acute and chronic symptoms. The armamentarium of therapies to prevent attacks consists of several monoclonal antibodies (mAbs) approved to treat AQP4-IgG-seropositive disease and several off-label therapies used for patients with either seropositive or seronegative disease. There is limited evidence to guide treatment decision-making, including which therapies to use first line, when to switch, and when to use monotherapy vs combination therapy. In addition, therapies with the greatest demonstrated safety and efficacy in NMOSD are costly and may not be accessible to all patients. Moreover, the results of the patient survey revealed significant clinical and financial burdens to patients with NMOSD including frequent attacks, delays in therapy initiation, need for urgent care and repeat hospitalizations, new and worsening symptoms, accumulating disability, and difficulties affording care. As such, key stakeholders must weigh them against the substantial economic costs of untreated or suboptimal treatment of disease. DISCLOSURES: Dr Wingerchuk has served on the advisory board or panel for Alexion, Biogen, Genentech, Horizon, Mitsubishi Tanabe, Novartis, Roche, UCB, and Viela Bio and has received grants of research support from Alexion. Dr Weinshenker has served as a consultant or on the advisory board or panel for Alexion, Genentech, Horizon, Mitsubishi Tanabe, Roche, UCB, and Viela Bio, served on the speakers bureau or other promotional education for Genentech and Roche, and has received royalties from RSR Ltd.