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The spectrum of anti-contactin-associated protein-like 2 (CASPR2) antibody-associated disease is expanding and the involvement of cerebellum was reported in the past few years. We report a 45-year-old male with chronically progressive cerebellar ataxia. CASPR2 antibodies were detected in his serum and cerebellar atrophy was observed on MRI. His symptoms improved prominently with steroids and intravenous immunoglobulins. 23 cases with CASPR2 antibodies and cerebellar ataxia were identified from previous publications. Most of patients showed acute or subacute onset with other typical presentations of anti-CASPR2 antibody-associated disease, such as limbic encephalitis. Immunotherapy was effective in the majority of patients., (Copyright © 2021. Published by Elsevier B.V.)

Background & Aims: The association between chronic inflammation and gastric carcinogenesis is well established, but it is not clear how immune cells and cytokines regulate this process. We investigated the role of interleukin 27 (IL27) in the development of gastric atrophy, hyperplasia, and metaplasia (preneoplastic lesions associated with inflammation-induced gastric cancer) in mice with autoimmune gastritis., Methods: We performed studies with TxA23 mice (control mice), which express a T-cell receptor against the H+/K+ adenosine triphosphatase α chain and develop autoimmune gastritis, and TxA23xEbi3 -/- mice, which develop gastritis but do not express IL27. In some experiments, mice were given high-dose tamoxifen to induce parietal cell atrophy and spasmolytic polypeptide-expressing metaplasia (SPEM). Recombinant IL27 was administered to mice with mini osmotic pumps. Stomachs were collected and analyzed by histopathology and immunofluorescence; we used flow cytometry to measure IL27 and identify immune cells that secrete IL27 in the gastric mucosa. Single-cell RNA sequencing was performed on immune cells that infiltrated stomach tissues., Results: We identified IL27-secreting macrophages and dendritic cell in the corpus of mice with chronic gastritis (TxA23 mice). Mice deficient in IL27 developed more severe gastritis, atrophy, and SPEM than control mice. Administration of recombinant IL27 significantly reduced the severity of inflammation, atrophy, and SPEM in mice with gastritis. Single-cell RNA sequencing showed that IL27 acted almost exclusively on stomach-infiltrating CD4+ T cells to suppress expression of inflammatory genes., Conclusions: In studies of mice with autoimmune gastritis, we found that IL27 is an inhibitor of gastritis and SPEM, suppressing CD4+ T-cell-mediated inflammation in the gastric mucosa., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective Limbic encephalitis (LE) is an inflammatory condition of the limbic system that has an acute or subacute onset. Several types of antibodies are related to the onset of LE, including anti-N-methyl D-aspartate receptor (NMDAR) antibodies and voltage-gated potassium channel (VGKC)-complex antibodies. However, the characteristics and prevalence of LE remain unclear, especially in Asian cohorts, due to the rarity. We aimed to survey their characteristics. Materials and Methods Data of 30 cases clinically defined as "definite autoimmune LE" (based on the standard criteria) were retrospectively collected. These patients were categorized into four subtypes: NMDAR (+) (n=8), VGKC (+) (n=2), antibodies related to paraneoplastic syndrome (n=2), and an antibody-negative group (uncategorized) (n=18). Results LE is rare in Japan, and affected only 30 of 16,759 hospital patients (0.2%) over a ten-year period. The NMDAR (+) group showed distinctive symptoms, while the other three groups had similar indications. Brain MRI indicated significant medial temporal lobe atrophy at one year follow up after discharge. The prevalence of cognitive dysfunction as a complication was 64% (9/14). First-line immunotherapy resulted in a good outcome. A drastic improvement was seen from 4.0±1.1 to 1.1+ on the modified Rankin Scale. A good treatment outcome was observed in all groups (NMDAR, VGKC, and uncategorized), suggesting the importance of an early clinical diagnosis and the early initiation of treatment. Furthermore, we reviewed 26 cases that were clinically diagnosed as definitive autoimmune LE in previous case reports. Conclusion Our findings show that the establishment of a clinical diagnosis based on the clinical criteria of definitive autoimmune LE is important for the initiation of immunotherapy.

Aim: To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection., Methods: Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology., Results: Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively)., Conclusions: H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aging of the immune system, or immunosenescence, is characterized by changes in T cell subsets, cellular and molecular level alterations and thymic atrophy, resulting in a decline of T and B cell function. These alterations have been shown to be accompanied by a loss of ability to recognize "self" and "foreign" antigens. Therefore the development of autoimmune responses like production of autoantibodies has been hypothesized to be secondary to thymus involution with a decline of naïve T cells and accumulation of clonal T cells with activation due to "neoantigens" during the aging process. Altered apoptosis and altered T cell homeostasis have been emphasized to promote a chronic inflammatory state and lead to the concept of a immune-risk phenotype. However, it has to be proven which kinds of mechanisms turn the immune system to manifest autoimmune disease and how speculated defects in T cell differentiation and interaction leading to premature aging of the immune system may contribute to the development of autoimmune diseases.

Thyroid atrophy, rather than goitre, is a characteristic feature of myxoedematous cretinism but its cause and nature are unknown. In this study, purified IgG fractions of serum from patients with myxoedematous endemic cretinism inhibited thyrotropin-induced DNA synthesis in guineapig thyroid segments in a sensitive cytochemical bioassay. IgG from patients with euthyroid neurological endemic cretinism or from normal subjects did not inhibit thyroid growth. Furthermore, in myxoedematous subjects, the presence of the thyroid-growth-blocking immunoglobulins showed a positive relation with thyroid atrophy found on ultrasound. These findings provide a pathogenic basis for the variable clinical expression of endemic cretinism.

Multiple immunological abnormalities have been demonstrated in fourteen patients with evidence in the blood-film of hyposplenism due to splenic atrophy. Reduction in spleen size was confirmed radiologically, and impairment of phagocytosis by the spleen was demonstrated by studying the survival and fate of chemically damaged autologous red blood-cells. Eight of the patients had intestinal malabsorption, and there was a high frequency of autoimmune disease in the remainder. Although patients with splenic atrophy showed little evidence of impairment of normal immune responses, there was a high frequency of autoantibody formation. There is thus an association between widespread immunological disturbances, notably autoimmunity, and splenic atrophy.