Autoimmune Antibodies Research Articles

Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?

Primary biliary cholangitis (PBC) is an autoimmune liver disease. During the diagnostic process, the patient's autoimmune antibodies are routinely examined. Approximately 20% of PBC patients have positive anti-centromere antibody (ACA). We evaluated the clinical characteristics of ACA-positive and ACA-negative PBC patients to explain the differences in disease progression between these two groups. Retrospective data from 961 PBC patients at Beijing Youan Hospital from 2010 to 2019 were gathered and separated into two groups based on ACA positivity. We collected and evaluated clinical laboratory indices, gastroscopy findings, and liver function assessments. In addition, 60 liver biopsies were available for comparison between the 2 groups. Pathologists staged the histological findings using the Ludwig staging criteria and Nakanuma staging and grading. Immunohistochemical staining was also performed on liver biopsies to examine the expression of cytokeratin 7 (CK7) in the tissue. A synthesis of clinical indicators in the large cohort showed that alanine transaminase, aspartate aminotransferase, total bilirubin, IgG, white blood cell, and platelet were significantly lower in the ACA-positive group, indicating that the overall status of liver injury was more moderate in the ACA-positive group. Additionally, ACA-positive patients in the non-cirrhotic group were more likely to present with gastroesophageal varices related to portal hypertension. Finally, analysis of pathologic findings showed that parameters were mostly comparable in the two groups, but CK7 differed and was more significantly lower in the ACA-positive group in albumin-bilirubin grade 2 and 3 patients. In summary, we characterized and compared the clinical features of ACA-positive and ACA-negative PBC patients, corroborating previous studies on the relationship between ACA positivity and portal hypertension cross-sectionally. It suggested that gastroesophageal varices might happen in the earlier course of PBC natural progression in the ACA-positive group.

Prevalence of comorbid autoimmune diseases and antibodies in newly diagnosed multiple sclerosis patients

BackgroundDiagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS.MethodsIn this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank.ResultsWe identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren’s syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis.ConclusionOur study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life.

Case report: orthostatic hypotension as the first presentation of progressive encephalomyelitis with rigidity and myoclonus (PERM) with multiple autoimmune antibodies

IntroductionStiff person syndrome (SPS) is a rare disease characterized by axial and lower-extremity muscle rigidity, muscle spasm, and pain. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a variant of SPS. This case is particularly notable for its uncommon initial symptom: orthostatic hypotension, coupled with the presence of multiple antibodies. Such a presentation is a rarity in the context of PERM, thus providing a fresh and unique angle for both diagnosis and treatment.Case presentationThis case presents a 71-year-old man who was ultimately diagnosed with progressive encephalomyelitis with rigidity and myoclonus (PERM). His initial symptom was orthostatic hypotension, and we detected multiple antibodies such as GlyR antibody, GAD antibody, GM1-IgG and GQ1b-IgG in his serum. The patient showed partial response to glucocorticoid and immunoglobulin therapies, but as the disease recurred and progressed, plasma exchange, rituximab, and cyclophosphamide immunosuppressive therapy was administered, the prognosis remained poor. During follow-up after treatment, the patient developed pulmonary embolism and cardiac arrest, and died.ConclusionPERM exhibits diverse manifestation and pathogenic mechanisms. Immune heterogeneity affects clinical symptoms and prognosis. Cases of PERM combined with orthostatic hypotension and various antibodies have rarely been reported, the incidence and the specific mechanism is unknown, underscoring the need for further research. This case report underscores the importance of recognizing the diverse clinical presentations of PERM and the challenges in its diagnosis and management. It highlights autonomic dysfunction may be as the initial symptom of PERM. Moreover, it emphasizes the limitations of current treatment modalities and the necessity for further research to elucidate the underlying mechanisms and optimize therapeutic approaches for this debilitating autoimmune condition.

Analysis of immunological and biochemical parameters after booster dose vaccination using protein-based and inactivated virus vaccine for safety

IntroductionHeterologous vaccines enhance the immune response to new variants and allow flexibility in booster administration when the original vaccine is unavailable. Studies show that heterologous boosters can generate comparable or superior antibody responses compared to homologous boosters. Considering rare side effects is essential in evaluating COVID-19 vaccines, especially those associated with ChAdOx1-S (AstraZeneca) and Ad26.COV2.S (Janssen), including blood clotting and idiopathic thrombocytopenia. Severe side effects, such as myocarditis and pericarditis, may occur after Pfizer or Moderna boosters but are rare. MethodsThis study administered two vaccines: the Sinopharm inactivated virus vaccine and the Razi-CoV-Pars (RCP) booster. Various evaluations included biochemical markers, coagulation factors, autoimmune antibodies, and antibodies against concerning variants. ResultsAll 90 participants exhibited a notable rise in antibody levels against the variant of concern (VOC). Participants receiving the Razi-CoV-Pars booster after Sinopharm/BBIBP-CorV showed significantly higher antibody levels (Wuhan ∼ 3.25 times, Delta ∼4 times, Omicron ∼ 14 times) compared to those receiving Sinopharm's homologous vaccine. No significant changes (P: <0.05) were found in LDH, CPK, CK-MB, ANA, and Anti-CCP levels. However, individuals receiving Sinopharm's booster after two doses showed a significant increase (4 cases) in D-Dimer levels. ConclusionThe Razi-CoV-Pars vaccine demonstrates a favorable safety profile and promising potential as an effective booster against current variants, particularly due to its significant protective titer against Omicron.

L-arginine, aminoguanidine and mesenchymal stem cells reduce the level of endoplasmic reticulum stress markers and D-dimer in the lungs of mice with antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by damage to the intima of the microcirculatory blood vessels as a result of the formation of autoimmune antibodies to phospholipids of cell membranes. Recent data indicate a possible link between the occurrence of autoimmune diseases and endoplasmic reticulum stress, impaired nitric oxide availability, high plasma D-dimer level. The aim of the study was to estimate the effect of nitric oxide synthesis modulators L-arginine and aminoguanidine, and mesenchymal stem cells on the level of inositol-requiring enzyme-1a (IRE-1a), glucose-regulated protein 78 (GRP-78) as ER stress markers, and the level of D-dimer in the lung tissue of female BALB/c line mice with experimental APS induced with cardiolipin administration. 30 experimental animals were divided into five groups: 1 – control animals; 2 – mice with APS; 3 – mice with APS, injected intraperitoneally with L-arginine hydrochloride (25 mg/kg) and aminoguanidine (10 mg/kg); 4 – mice with APS, injected intraperitoneally with stem cells (5×106/kg); 5 – mice with APS, injected with L-arginine hydrochloride, aminoguanidine and stem cells in combination. After 10 days post APS formation animals were removed from the experiment, proteins were extracted from the lung tissue and their level was determined with Western blotting. It was established that in group with APS the levels of IRE-1, GRP-78 and D-dimer were substantially increased as compared to the control group. After separate administration of both arginine with aminoguanidine and MSC, as well as with their combined use, the level of IRE-1, GRP-78 and D-dimer decreased compared to the indices in animals with induced APS. The obtained data indicated that this effect is probably due to the reduction of ER stress through iNOS inhibition and the anti-inflammatory action of MSCs. Keywords: aminoguanidine, antiphospholipid syndrome, D-dimer, endoplasmic reticulume stress, GRP-78, IRE-1, L-arginine, lung, mesenchymal stem cells

Impact of second-generation antipsychotics monotherapy or combined therapy in cytokine, lymphocyte subtype, and thyroid antibodies for schizophrenia: a retrospective study

BackgroundSchizophrenia (SCZ) shares high clinical relevance with the immune system, and the potential interactions of psychopharmacological drugs with the immune system are still an overlooked area. Here, we aimed to identify whether the second-generation antipsychotics (SGA) monotherapy or combined therapy of SGA with other psychiatric medications influence the routine blood immunity biomarkers of patients with SCZ.MethodsMedical records of inpatients with SCZ from January 2019 to June 2023 were retrospectively screened from June 2023 to August 2023. The demographic data and peripheral levels of cytokines (IL-2, IL-4, IL-6, TNF-α, INF-γ, and IL-17 A), lymphocyte subtype proportions (CD3+, CD4+, CD8 + T-cell, and natural killer (NK) cells), and thyroid autoimmune antibodies (thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb)) were collected and analyzed.Results30 drug-naïve patients, 64 SGA monotherapy (20 for first-episode SCZ, 44 for recurrent SCZ) for at least one week, 39 combined therapies for recurrent SCZ (18 with antidepressant, 10 with benzodiazepine, and 11 with mood stabilizer) for at least two weeks, and 23 used to receive SGA monotherapy (had withdrawn for at least two weeks) were included despite specific medication. No difference in cytokines was found between the SGA monotherapy sub-groups (p > 0.05). Of note, SGA monotherapy appeared to induce a down-regulation of IFN-γ in both first (mean [95% confidence interval]: 1.08 [0.14–2.01] vs. 4.60 [2.11–7.08], p = 0.020) and recurrent (1.88 [0.71–3.05] vs. 4.60 [2.11–7.08], p = 0.027) episodes compared to drug-naïve patients. However, the lymphocyte proportions and thyroid autoimmune antibodies remained unchanged after at least two weeks of SGA monotherapy (p > 0.05). In combined therapy groups, results mainly resembled the SGA monotherapy for recurrent SCZ (p > 0.05).ConclusionThe study demonstrated that SGA monotherapy possibly achieved its comfort role via modulating IFN-γ, and SGA combined therapy showed an overall resemblance to monotherapy.

12233 Weight Gain Following Thyroidectomy For Benign Conditions

Abstract Disclosure: A. Krueger: None. A. Chiu: None. S. Pabich: None. S. Syed: None. A. Poloju: None. S. Holoubek: None. Background: Weight gain is a common complaint of patients with hypothyroidism irrespective of etiology that causes dissatisfaction and decreased quality. Patients often report thyroidectomy as the precipitating event leading to subsequent weight gain and resistance to weight loss. Reported data on body weight changes following surgery are conflicting and there is limited literature on patients with benign pathologies. The average weight gain in the general population has been reported as 0.5/year. The primary outcome of this study was to determine if patients undergoing thyroidectomy for benign conditions experienced greater than expected weight gain compared to the general population when TSH values were controlled. Secondary outcomes assessed were whether pre-operative disease pathology or antibody status affected weight changes. Methods: A retrospective review was performed on 325 patients undergoing total thyroidectomy for benign conditions from January 2015 to December 2020 using the University of Wisconsin Thyroid Surgery Database. The weight change was determined from the time of surgery to the following intervals: 1-2 years, 2-5 years, and &amp;gt;5 years. Study groups were then compared by pathology and presence of antibodies. Exclusion criteria included age &amp;lt;18 years, thyroid cancer, pregnancy within one-year post-surgery, incomplete weight or TSH data, post-operative gastric-bypass surgery, and patients who were not euthyroid pre- and post-op. Results: Our patient population (n=219) gained a mean of 1.58 kg at the 1-2 year interval. There was no significant difference in weight gain based on pathology or antibody status. At the 2-5 year interval, the average weight gain was 2.05 kg and those with antibodies had significantly higher weight gain. Patients with TPO antibodies (n=34) gained a mean weight of 4.58 kg, and those with TRAB and or TSI antibodies (n=17) gained a mean weight of 4.67 kg. Those with both types of antibodies (n=10) did not have any significant weight gain. Conclusion: Conservatively, the expected weight gain of the general population over 2-5 years is 2.5 kg. Using a logistic regression model, patients with autoimmune thyroid disease had twice the odds of gaining more weight than expected by 2-5 years. The presence of auto-immune thyroid antibodies may serve as a target population for intensive weight management programs following surgery. Presentation: 6/1/2024

12233 Weight Gain Following Thyroidectomy For Benign Conditions

Abstract Disclosure: A. Krueger: None. A. Chiu: None. S. Pabich: None. S. Syed: None. A. Poloju: None. S. Holoubek: None. Background: Weight gain is a common complaint of patients with hypothyroidism irrespective of etiology that causes dissatisfaction and decreased quality. Patients often report thyroidectomy as the precipitating event leading to subsequent weight gain and resistance to weight loss. Reported data on body weight changes following surgery are conflicting and there is limited literature on patients with benign pathologies. The average weight gain in the general population has been reported as 0.5/year. The primary outcome of this study was to determine if patients undergoing thyroidectomy for benign conditions experienced greater than expected weight gain compared to the general population when TSH values were controlled. Secondary outcomes assessed were whether pre-operative disease pathology or antibody status affected weight changes. Methods: A retrospective review was performed on 325 patients undergoing total thyroidectomy for benign conditions from January 2015 to December 2020 using the University of Wisconsin Thyroid Surgery Database. The weight change was determined from the time of surgery to the following intervals: 1-2 years, 2-5 years, and &amp;gt;5 years. Study groups were then compared by pathology and presence of antibodies. Exclusion criteria included age &amp;lt;18 years, thyroid cancer, pregnancy within one-year post-surgery, incomplete weight or TSH data, post-operative gastric-bypass surgery, and patients who were not euthyroid pre- and post-op. Results: Our patient population (n=219) gained a mean of 1.58 kg at the 1-2 year interval. There was no significant difference in weight gain based on pathology or antibody status. At the 2-5 year interval, the average weight gain was 2.05 kg and those with antibodies had significantly higher weight gain. Patients with TPO antibodies (n=34) gained a mean weight of 4.58 kg, and those with TRAB and or TSI antibodies (n=17) gained a mean weight of 4.67 kg. Those with both types of antibodies (n=10) did not have any significant weight gain. Conclusion: Conservatively, the expected weight gain of the general population over 2-5 years is 2.5 kg. Using a logistic regression model, patients with autoimmune thyroid disease had twice the odds of gaining more weight than expected by 2-5 years. The presence of auto-immune thyroid antibodies may serve as a target population for intensive weight management programs following surgery. Presentation: 6/1/2024

Cognitive impairments in autoimmune encephalitis: the role of autoimmune antibodies and oligoclonal bands.

The presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a pivotal diagnostic marker for multiple sclerosis (MS). These bands play a crucial role in the diagnosis and understanding of a wide array of immune diseases. In this study, we explore the relationship between the cognitive profile of autoimmune encephalitis (AIE) and the presence of OCBs in CSF, with a particular emphasis on NMDA receptor antibodies. We studied a cohort of 21 patients across five tertiary centers, segregated into two distinct categories. One group comprised individuals who tested positive only for autoimmune encephalitis antibodies indicative of encephalitis, while the other group included patients whose CSF was positive for both autoimmune encephalitis antibodies and OCBs. Our investigation focused primarily on cognitive functions and behavioral alterations, supplemented by auxiliary diagnostic assessments such as CSF cell count, magnetic resonance imaging (MRI), and electroencephalogram (EEG) results, evaluated for the two patient groups. To validate our findings, we employed statistical analyses such as Fisher's exact test with Benjamini-Hochberg correction. Our study included 21 patients, comprising 14 who were presented with only autoimmune encephalitis antibodies, and 7 who were dual-positive. Among these patients, we focused on those with NMDA receptor antibodies. Of these, five were dual positive, and nine were positive only for NMDA receptor antibodies. The dual-positive NMDA group, with an average age of 27 ± 16.47 years, exhibited significantly higher CSF cell counts (p=0.0487) and more pronounced language and attention deficits (p= 0.0264). MRI and EEG results did not differ significantly between the groups. Our results point to OCBs as an additional marker of disease severity in AIE, especially in NMDA receptor-antibody positive patients, possibly indicating a broader inflammatory process, as reflected in elevated CSF lymphocytes. Regular testing for OCBs in cases of suspected AIE may aid in disease prognosis and identification of patients more prone to language and attention disorders, improving diagnosis and targeting treatment for these cognitive aspects.

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

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

Histologic Features of Liver Injury Associated With SARS-CoV-2 Messenger RNA Vaccines.

Many drugs can induce liver injury; however, vaccine-induced liver injury is a rare phenomenon. SARS-CoV-2 messenger RNA (mRNA) vaccines are now widely administered, and clinical evidence of liver injury has been reported. To characterize the histologic features of SARS-CoV-2 mRNA vaccine-associated liver injury. Thirteen liver biopsies from 12 patients with elevated liver enzymes clinically favored to be secondary to SARS-CoV-2 mRNA vaccine were identified between 2021 and 2022. Demographics, clinical information, and histologic features of liver biopsies were reviewed. All patients (median age, 58 years; M:F = 4:8) received at least 1 dose of SARS-CoV-2 mRNA vaccines (7 Pfizer and 5 Moderna). Four patients had a history of liver disease. Nine patients developed symptoms between 1 day and 2 months after receiving the vaccine dose. Viral serologies were negative. Drug-induced liver injury was thought to be less likely clinically in the 3 patients who had started new medications. Autoimmune antibodies were detected in 9 patients. Moderate to severe active hepatitis was the dominant histologic pattern of injury (9 of 13 biopsies; 69%). Resolving hepatitis, cholestatic hepatitic injury, and bile duct injury were identified in 1 biopsy each. All patients recovered spontaneously or with steroid therapy except one patient who developed autoimmune hepatitis. Moderate to severe active hepatitis is commonly observed in SARS-CoV-2 mRNA vaccine-associated liver injury, and female patients may be more susceptible to injury. Liver injury resolves spontaneously or with steroid treatment. In rare cases, these vaccines may trigger an underlying immune condition.

A novel nonsense mutation c.747C>G in the NEUROD1 gene detected within a Chinese family affected by maturity-onset diabetes of the young type 6.

Highlights Maturity-onset diabetes of the young type 6 (MODY6) is a rare form of monogenic diabetes mellitus due to NEUROD1 gene mutation on chromosome 2q32. A 21-year-old woman exhibiting weight loss, polyuria, and hyperglycemia was initially misdiagnosed with type 1 diabetes mellitus. Considering the early-onset age, a three-generation family history of diabetes, and negative autoimmune antibodies, a MODY diagnosis was suspected. Genetic analysis revealed that she inherited a novel heterozygous nonsense NEUROD1 mutation c.747C>G (p.Tyr249*) from her father. Correct MODY6 diagnosis facilitates appropriate interventions.

Immunometabolic effects of lactate on humoral immunity in healthy individuals of different ages

Aging is characterized by chronic systemic inflammation and metabolic changes. We compare the metabolic status of B cells from young and elderly donors and found that aging is associated with higher oxygen consumption rates, and especially higher extracellular acidification rates, measures of oxidative phosphorylation and of anaerobic glycolysis, respectively. Importantly, this higher metabolic status, which reflects age-associated expansion of pro-inflammatory B cells, is found associated with higher secretion of lactate and autoimmune antibodies after in vitro stimulation. B cells from elderly individuals induce in vitro polarization of CD4+ T cells from young individuals into pro-inflammatory CD4+ T cells through metabolic pathways mediated by lactate, which can be inhibited by targeting lactate enzymes and transporters, as well as signaling pathways supporting anaerobic glycolysis. Lactate also induces immunosenescent B cells that are glycolytic, express transcripts for multiple pro-inflammatory molecules, and are characterized by a higher metabolic status. These results altogether may have relevant clinical implications and suggest alternative targets for therapeutic interventions in the elderly and patients with inflammatory conditions and diseases.

Evaluation of autoimmune liver disease antibodies in hepatitis patients.

Autoimmune hepatitis (AIH) is characterized by the presence of auto-antibodies and high blood immunoglobulin G (IgG) levels. In this study, the line immunoassay (LIA) was designed to assess various autoantibodies. In total, 1371 patients who underwent autoimmune liver disease antibody testing between July 2019 and November 2022 were enrolled. Autoantibodies including antinuclear antibody (ANA) and anti-mitochondrial antibody (AMA) were tested, and clinical data were collected. Statistical analyses were performed by categorizing the data based on diagnosis and IgG quantification separately. A scoring system was applied to identify individuals with AIH. Patients were also classified into the AIH and non-AIH groups. The positivity rate for ANA was 80.2% in the AIH group. The IgG-high group had a high likelihood of the presence of detectable autoantibodies, with anti-Ro-52 being the most frequently detected antibody using LIA. The "Consider AIH" and "AMA" groups had 3-4 times more patients in the IgG-high group than in the "Not Considered" group. Among autoantibodies, the prevalence of ANA was the highest. As per LIA results, anti-Ro-52 was the most prevalent. AIH cannot be diagnosed based on IgG levels alone and must be distinguished via autoantibody testing. Therefore, extensive testing, including autoantibodies, IgG, ANA, and liver enzyme levels, will help accurately diagnose AIH.

Patterns of Neuropsychiatric Manifestations of Ovarian Teratomas: A Systematic Review of Case Reports.

Ovarian teratomas are germ cell tumors composed of multiple cell types. Ovarian teratomas may express antigens found in the nervous system or neuroendocrine proteins. These neural antigens and neuroendocrine proteins may lead to an autoimmune response with associated encephalitis. There are a growing number of case reports of autoimmune encephalitis in patients with ovarian teratomas. However, the patterns of neuropsychiatric manifestations of ovarian teratomas associated with encephalitis have not been established. The aim of this article is to conduct a systematic review to determine the patterns of neuropsychiatric manifestations of ovarian teratoma-associated encephalitis, focusing on their frequency and clinical course. Thirty-three case reports were collected and analyzed for a systematic review. The studies were full-text, peer-reviewed journal publications from April 2014 to April 2024. Fifty-eight patients were included in our study. The age group of 22-35 years old was the most reported, with 25 (43.1%) patients. The most commonly reported symptoms were memory impairment in 29 (50%) patients, hallucinations in 25 (43.1%) patients, and aggressive behavior in 23 (39.7%) patients. Neuropsychiatric symptoms had a prodromal phase of flu-like symptoms in 31 (53.4%) patients. The neuropsychiatric symptoms preceded the diagnosis of ovarian teratoma in 57 (98.3%) patients. In 53 (91.4%) patients, patients did not respond to psychiatric medications. Autoimmune antibodies to neural antigens were found in 45 (77.6%) patients, with 25 (43.1%) patients having neural tissue present in the teratoma. Treatment of the underlying teratoma and encephalitis led to full recovery in 37 (63.8%) patients. However, long-term outcomes such as relapse and mortality were discussed in only 11 (19.0%) patients. Findings suggest that neuropsychiatric symptoms correlate with teratoma-associated encephalitis and often precede tumor detection. The treatment of the teratoma led to full recovery of the neuropsychiatric manifestations; however, the long-term outcomes of the patients need to be further studied. Future research is needed on the prognosis of patients with neuropsychiatric manifestations of ovarian teratoma.

Prevalence and clinical significance of anti-SSA antibody in the Chinese health screening population.

Anti-SSA antibodies are non-organ-specific autoantibodies highly prevalent in various autoimmune diseases. This study primarily investigated the prevalence of anti-SSA antibodies in the health screening population. Additionally, we explored the clinical features of the anti-SSA antibody-positive population and evaluated the development of connective tissue diseases (CTD) over the years in individuals with anti-SSA antibodies for whom follow-up was available. 64045 individuals without a history of CTD from 2013 to 2022 who visited Peking Union Medical College Hospital for health screening were screened for autoimmune antibodies. 1.7% (1091/64045) of the Chinese health screening population were positive for anti-SSA antibodies, with a prevalence of 0.9% (290/33829) in men and 2.7% (801/30216) in women. Compared with matched autoantibody-negative controls, anti-SSA antibody-positive individuals had higher levels of serological abnormalities including erythrocyte sedimentation rate (ESR) [10 (6-15) mm/h vs. 7 (4-12) mm/h, p<0.0001], rheumatoid factor (RF) [7.15 (4.30-16.90) IU/ml vs. 5.00 (3.20-7.90) IU/ml, p<0.0001], and Immunoglobulin G [13.09 (11.20-15.45) g/L vs. 11.34 (9.85-13.18) g/L, p<0.0001], and lower levels of white blood cells (WBC) (5.49 ± 1.50 *109/L vs. 5.82 ± 1.49 *109/L, p<0.0001). Additionally, they had a higher proportion of coexisting thyroid autoantibodies, including anti-thyroid peroxidase antibodies (TPO-Ab) (17.1% vs. 11.3%, p<0.0001) and anti-thyroglobulin antibodies (Tg-Ab) (17.8% vs. 11.0%, p<0.0001). Among the 381 subjects who were anti-SSA positive and followed up for a median of 4.6 years, 146 (38.3%) individuals developed CTD, including 68 (17.8%) cases of primary Sjögren syndrome (pSS), 10 (2.6%) cases of rheumatoid arthritis (RA), 5 cases (1.3%) of systemic lupus erythematosus (SLE), and 59 (15.5%) cases of undifferentiated connective tissue disease (UCTD). 235 (61.7%) individuals did not develop CTD over a median time of 5.9 (2.9-8.1) years after the earliest autoantibody detection. Elevated ESR (>20mm/h), RF positivity (>20 IU/ml), and female gender were identified as independent risk factors for CTD among the anti-SSAantibody-positive individuals. Anti-SSA antibodies were found in 17 among approximately 1000 individuals without a history of autoimmune diseases. Anti-SSA antibody-positive individuals are advised to periodically monitor thyroid function. Elevated ESR (>20mm/h), female gender, and rheumatoid factor positivity may delineate a high-risk cohort for CTDs.

Autoimmune glial fibrillary acidic protein astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome: A case report and literature review.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disease of the central nervous system that affects the meninges, brain, spinal cord, and optic nerves. GFAP astrocytopathy can coexist with a variety of antibodies, which is known as overlap syndrome. Anti-NMDAR-positive encephalitis overlap syndrome has been reported; however, encephalitis overlap syndrome with both anti-NMDAR and sulfatide-IgG positivity has not been reported. The patient was a 50-year-old male who was drowsy and had chills and weak limbs for 6 months. His symptoms worsened after admission to our hospital with persistent high fever, dysphoria, gibberish, and disturbance of consciousness. Positive cerebrospinal fluid NMDA, GFAP antibodies, and serum sulfatide antibody IgG were positive. Autoimmune GFAP astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome. In addition to ventilator support and symptomatic supportive treatment, step-down therapy with methylprednisolone (1000 mg/d, halved every 3 days) and pulse therapy with human immunoglobulin (0.4 g/(kg d) for 5 days) were used. After 6 days of treatment, the patient condition did not improve, and the family signed up to give up the treatment and left the hospital. Patients with autoimmune GFAP astrocytopathy may be positive for anti-NMDAR and sulfatide-IgG, and immunotherapy may be effective in patients with severe conditions. Autoimmune GFAP astrocytopathy with nonspecific symptoms is rarely reported and is easy to be missed and misdiagnosed. GFAP astrocytopathy should be considered in patients with fever, headache, disturbance of consciousness, convulsions, and central infections that do not respond to antibacterial and viral agents. Autoimmune encephalopathy-related antibody testing should be performed as soon as possible, early diagnosis should be confirmed, and immunomodulatory therapy should be administered promptly.

Post-infectious Moyamoya Syndrome: A Review of Existing Scientific Literature From 2000 to 2023.

Moyamoya disease (MMD) is considered a primary disorder of an unknown etiology. In contrast, Moyamoya syndrome (MMS) refers to MMD associated with other underlying diseases, such as meningitis in childhood, neurofibromatosis type II, Down syndrome, cranial irradiation, and different types of anemias, particularly hemoglobinopathies. We aimed to provide a comprehensive clinicopathological overview of MMS. All case reports and case series published from 2000 to 2023 pertaining to MMD were included in the study. Case studies, original articles, editorials, letters to editors, and clinical images were excluded. The search was conducted using the Boolean operators ("AND" and "OR") on PubMed and Google Scholar. A total of 13 case reports and one case series study were included. The study suggests infection might be a trigger in susceptible individuals. The autoimmune antibody findings (anti-double stranded DNA IgG) suggest a potential autoimmune component in some cases. There were diverse presentations and outcomes of post-infectious MMS, with a striking predominance of pediatric cases (66.66%) and a possible female predominance. Both computerized tomography (CT) and magnetic resonance imaging (MRI) showed evidence of restricted blood flow. CT showed that stenosis, occlusion, and collateral formation were frequent vascular findings, but often unspecified in severity. Infarction, hypodensities, and hematoma were the most common parenchymal findings (22.22% each). The findings on MRI were stenosis (50%) and collateral formation (44.44%). Infarction was the most common finding (66.66%) in parenchyma. Hydrocephalus, encephalomalacia, and atrophy were less frequent. Lesions were most frequent in the internal carotid artery (66.66%),middle cerebral artery (66.66%), and anterior cerebral artery (50%). Lesions were less frequent in the posterior cerebral, vertebral, and basilar arteries. The frontal lobe (38.89%) and basal ganglia (33.33%) were commonly affected parenchymal regions. The most common risk factor was human immunodeficiency virus (HIV) infection (50%), followed by trisomy 21, cryptococcal, and other types of meningitides. Aspirin (50%) and antiretroviral therapy (38.89%) were the cornerstones of treatment for MMS. This review accentuates the noteworthy obstacles presented by post-infectious MMS, especially its catastrophic effect on children and its correlation with HIV/AIDS. According to our elaborate literature search using PubMed and Google Scholar, this is the first narrative review in the existing scientific literature summarizing the literature on post-infectious MMS.

The Implication of Elevated Serum Myoglobin Level in Acute Diabetic Complications of Ketoacidosis and Hyperglycemic Hyperosmolar State: A Real-World Study.

To investigate the implications of elevated myoglobin (MYO) in acute diabetic conditions of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). This study integrates in-patient data from Shanghai Pudong Hospital from 2019 to 2023. Laboratory data were compared between stable T2D patients (without acute diabetic complications), DKA, and HHS patients. The multilinear regression explored variables relevant to the elevated MYO in DKA and HHS. The dynamics of MYO, the survival rate, and associated risk factors in HHS were determined. Except for triglyceride, procalcitonin, low-density lipoprotein, islet cell autoimmune antibodies, N-terminal Pro-brain natriuretic peptide (NT-ProBNP), and brain natriuretic peptide (BNP), there were significant differences in age, gender distribution, duration of diabetes, type of diabetes, and other referred laboratory data (p<0.05). The age, gender, creatine kinase (CK), estimated glomerular filtration rate (eGFR), and free triiodothyronine (FT3) in DKA, whereas osmolar, uric acid (UA), and cardiac troponin I (cTNI) in the HHS, were significant determinants of elevated MYO, respectively (p<0.05). The dynamic of MYO in HHS was in line with the survival trend, where the percentage of death was 29.73%, and aging with higher procalcitonin levels was a key risk factor. Besides, the cumulative survival rates between patients with or without bone fracture or muscle injury were substantially different. This real-world study demonstrated DKA and HHS potentially have unique causes for increased MYO. By utilizing the appropriate regression parameters, we could forecast the progression of increased MYO in groups of DKA and HHS, while based on risk factors of aging, severity of infection, and different MYO sources, we could predict the prognosis of HHS.

Vitamin D3 attenuates autoimmune thyroiditis by regulating Th17/Treg cell differentiation via YAP/JAK1/STAT1 axis

BackgroundAutoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated. MethodsAn experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis. ResultsAdministration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function. ConclusionVitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.