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In 2002, the Japan Pancreas Society (JPS) was the first in the world to propose diagnostic criteria for autoimmune pancreatitis (AIP). Since the concept of AIP has changed with the accumulation of AIP cases, the Research Committee of Intractable Pancreatic Diseases (RCIPD) provided by the Ministry of Health, Labour and Welfare of Japan and the JPS issued revised clinical diagnostic criteria of AIP in 2006. The Asan Medical Center of Korea also proposed diagnostic criteria for AIP in 2006. However, there are subtle but clinically challenging differences between the Japanese and Korean criteria. This inconsistency makes it difficult to compare data in studies from different centers and elucidate the characteristics of AIP. To reach a consensus on AIP, the RCIPD and the Korean Society of Pancreatobiliary Diseases established the following Asian criteria for the diagnosis of AIP: I-1. Imaging studies of pancreatic parenchyma show a diffuse/segmental/focally enlarged gland, occasionally with a mass and/or a hypoattenuation rim. I-2. Imaging studies of pancreaticobiliary ducts show diffuse/segmental/focal pancreatic ductal narrowing, often with stenosis of the bile duct. (Both I-1 and I-2 are required for diagnosis). II. Elevated level of serum IgG or IgG4, and detection of autoantibodies. III. Common lymphoplasmacytic infiltration and fibrosis, with abundant IgG4-positive cell infiltration. AIP should be diagnosed when criterion I and one of the other two criteria are satisfied, or when histology shows the presence of lymphoplasmacytic sclerosing pancreatitis in the resected pancreas. A diagnostic trial of steroid therapy can be applied carefully by expert pancreatologists only in patients fulfilling criterion I alone with negative diagnostic work-up results for pancreatobiliary cancer.

To determine the sensitivity and specificity of elevated serum IgG4 level for the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer, its main differential diagnosis. We measured serum IgG4 levels (normal 8-140 mg/dL) in 510 patients including 45 with AIP, 135 with pancreatic cancer, 62 with no pancreatic disease, and 268 with other pancreatic diseases. Sensitivity, specificity, and positive predictive values for elevated serum IgG4 (>140 mg/dL) for diagnosis of AIP were 76%, 93%, and 36%, respectively, and 53%, 99%, and 75%, respectively, for IgG4 of >280 mg/dL. Among subjects with elevated IgG4, non-AIP subjects (N = 32) differed from AIP subjects (N = 34) in that they were more likely to be female (45%vs 9%, P < 0.001), less likely to have serum IgG4 >280 mg/dL (13%vs 71%, P < 0.001), or elevation of total IgG (16%vs 56%, P < 0.001). Serum IgG4 levels were elevated in 13/135 (10%) pancreatic cancer patients; however, only 1% had IgG4 levels >280 mg/dL compared with 53% of AIP. Compared with AIP, pancreatic cancer patients were more likely to have CA19-9 levels of >100 U/mL (71%vs 9%, P < 0.001). Elevated serum IgG4 levels are characteristic of AIP. However, mild (<2-fold) elevations in serum IgG4 are seen in up to 10% of subjects without AIP including pancreatic cancer and cannot be used alone to distinguish AIP from pancreatic cancer. Because AIP is uncommon, IgG4 elevations in patients with low pretest probability of having AIP are likely to represent false positives.

Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy.

A history of autoimmunity that validates the experience of patients while challenging assumptions about the distinction between the normal and the pathological. Winner of the NSW Premier's History Award of the Arts NSW Autoimmune diseases, which affect 5 to 10 percent of the population, are as unpredictable in their course as they are paradoxical in their cause. They produce persistent suffering as they follow a drawn-out, often lifelong, pattern of remission and recurrence. Multiple sclerosis, lupus, rheumatoid arthritis, and type 1 diabetes—the diseases considered in this book—are but a handful of the conditions that can develop when the immune system goes awry. Intolerant Bodies is a unique collaboration between Ian Mackay, one of the prominent founders of clinical immunology, and Warwick Anderson, a leading historian of twentieth-century biomedical science. The authors narrate the changing scientific understanding of the cause of autoimmunity and explore the significance of having a disease in which one's body turns on itself. The book unfolds as a biography of a relatively new concept of pathogenesis, one that was accepted only in the 1950s. In their description of the onset, symptoms, and course of autoimmune diseases, Anderson and Mackay quote from the writings of Charles Dickens, Edgar Allan Poe, Joseph Heller, Flannery O'Connor, and other famous people who commented on or grappled with autoimmune disease. The authors also assess the work of the dedicated researchers and physicians who have struggled to understand the mysteries of autoimmunity. Connecting laboratory research, clinical medicine, social theory, and lived experience, Intolerant Bodies reveals how doctors and patients have come to terms, often reluctantly, with this novel and puzzling mechanism of disease causation.

Autoreactive inflammatory CD4+ T cells, such as T helper (Th)1 and Th17 subtypes, have been found to associate with the pathogenesis of autoimmune disorders. On the other hand, CD4+ Foxp3+ T regulatory (Treg) cells are crucial for the immune tolerance and have a critical role in the suppression of the excessive immune and inflammatory response promoted by these Th cells. In contrast, dendritic cells (DCs) and macrophages are immune cells that through their inflammatory functions promote autoreactive T‐cell responses in autoimmune conditions. In recent years, there has been increasing attention to exploring effective immunomodulatory or anti‐inflammatory agents from the herbal collection of traditional medicine. Berberine, an isoquinoline alkaloid, is one of the main active ingredients extracted from medicinal herbs and has been shown to exert various biological and pharmacological effects that are suggested to be mainly attributed to its anti‐inflammatory and immunomodulatory properties. Several lines of experimental study have recently investigated the therapeutic potential of berberine for treating autoimmune conditions in animal models of human autoimmune diseases. Here, we aimed to seek mechanisms underlying immunomodulatory and anti‐inflammatory effects of berberine on autoreactive inflammatory responses in autoimmune conditions. Reported data reveal that berberine can directly suppress functions and differentiation of pro‐inflammatory Th1 and Th17 cells, and indirectly decrease Th cell‐mediated inflammation through modulating or suppressing other cells assisting autoreactive inflammation, such as Tregs, DCs and macrophages.

Immune-mediated cerebellar ataxias (IMCAs) represent a group of disorders in which the immune system targets mainly the cerebellum and related structures. We address fundamental questions on the diagnosis and immunological pathogenesis of IMCAs, as illuminated by recent advances in the field. Various types of IMCAs have been identified, including post-infectious cerebellitis, Miller Fisher syndrome, gluten ataxia, paraneoplastic cerebellar degeneration (PCD), opsoclonus and myoclonus syndrome, and anti-GAD ataxia. In some cases, identification of several well-characterized autoantibodies points to a specific etiology in IMCAs and leads to a firm diagnosis. In other cases, various autoantibodies have been reported, but their interpretation requires a careful consideration. Indeed, some autoantibodies have only been documented in a limited number of cases and the causal relationship is not established. In order to facilitate an early treatment and prevent irreversible lesions, new entities have been defined in recent years, such as primary autoimmune cerebellar ataxia (PACA) and latent autoimmune cerebellar ataxia (LACA). PACA is characterized by autoimmune features which do not align with traditional etiologies, while LACA corresponds to a prodromal stage. LACA does not imply the initiation of an immunotherapy but requires a close follow-up. Concurrently, accumulation of clinical data has led to intriguing hypotheses regarding the mechanisms of autoimmunity, such as a pathogenesis of autoimmunity against synapses (synaptopathies), and the vulnerability of the entire nervous system when the immunity targets ion channels and astrocytes. The development of PCD in patients treated with immune-checkpoint inhibitors suggests that molecular mimicry specifically determines the direction of autoimmunity, and that the strength of this response is modulated by co-signaling molecules that either enhance or dampen signals from the antigen-specific T cell receptor.

Defective regulation of type I interferon response is associated with severe inflammatory phenotypes and autoimmunity. Type I interferonopathies are a clinically heterogenic group of Mendelian diseases with a constitutive activation of this pathway that might present as atypical, severe, early onset rheumatic diseases. Skin vasculopathy with chilblains and livedo reticularis, interstitial lung disease, and panniculitis are common. Recent studies have implicated abnormal responses to nucleic acid stimuli or defective regulation of downstream effector molecules in disease pathogenesis. As observed for IL1-β and autoinflammatory diseases, knowledge of the defects responsible for type I interferonopathies will likely promote the development of targeted therapy.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disease, which is characterized by the immune system attacking astrocytes in the central nervous system, resulting in inflammation and damage to the nervous system. We reported a 41-year-old female patient with only drowsiness for 3 months, who was, otherwise, healthy with no other signs of meningoencephalitis or myelitis. There were no obvious abnormalities in her neurological and ophthalmic tests. Brain magnetic resonance imaging (MRI) plain scan + enhancement with the gadolinium contrast agent revealed patchy hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, hyperintensity on T2-weighted fluid-attenuated inversion recovery in the left basal ganglia, corona radiata, and local septum pellucida, with no enhancement in the enhanced lesions. Cerebrospinal fluid (CSF) revealed white blood cell count of 5.00 × 10 6 /L, CSF protein of 828.53 mg/L, and glucose of 2.83 mmol/L. Aquaporin-4 (AQP4) antibody, N-methyl-D-aspartate receptor (NMDAR) antibody and GFAP antibody were all positive, whereas the remaining autoimmune encephalitis antibody tests were negative. Oncology screening [including head, chest, and whole-abdomen (involving the pelvic cavity) CT and tumor markers] did not reveal any obvious evidence of tumor presence. The patient received systemic treatment with high-dose intravenous injection of steroids combined with immunosuppressive agents, and the clinical and imaging features of the patients improved. To the best of our knowledge, reports on overlapping positivity of AQP4 antibody and NMDAR antibody in patients with GFAP astrocytopathy were still very rare. We hope to supplement the existing literature on this topic, review the relevant literature, and strive to increase the understanding toward GFAP astrocytopathy with overlapping autoimmune syndrome so as to enable early diagnosis and early treatment and to improve the clinical outcome of patients.

IL-17-producing T helper (Th17) cells have been implicated in the pathogenesis of many inflammatory and autoimmune diseases. Targeting the effector cytokines IL-17 and GM-CSF secreted by autoimmune Th17 cells has been shown to be effective for the treatment of the diseases. Understanding a molecular basis of Th17 differentiation and effector functions is therefore critical for the regulation of the pathogenicity of tissue Th17 cells in chronic inflammation. Here, we discuss the roles of proinflammatory cytokines and environmental stimuli in the control of Th17 differentiation and chronic tissue inflammation by pathogenic Th17 cells in humans and in mouse models of autoimmune diseases. We also highlight recent advances in the regulation of pathogenic Th17 cells by gut microbiota and immunometabolism in autoimmune arthritis.