Thymic Abnormalities Research Articles

Thymus Hyperplasia and Thymoma Type B in Patients with Myasthenia Gravis: Two case reports and Literature Review

Introduction: The thymus gland plays a pivotal role in immune system regulation, but conditions such as thymic hyperplasia (TH) and thymoma pose distinct clinical challenges due to their rarity and complex presentation in surgical practice. Both conditions can mimic similar symptoms, particularly in patients with Myasthenia Gravis (MG), where surgery serves as both a diagnostic and therapeutic intervention. This report presents the surgical management and outcomes of two MG patients with distinct thymic pathologies: TH and Type B thymoma, alongside a review of the relevant literature. Two MG patients were referred to our clinic for surgical intervention. The first patient underwent a standard sternotomy for the resection of TH, while the second patient underwent a mini-sternotomy for thymectomy targeting a Type B thymoma. Both procedures were completed successfully with uneventful postoperative courses. Surgical resection remains the gold standard for the treatment and definitive diagnosis of thymic gland abnormalities. Advances in surgical techniques, including minimally invasive approaches, offer excellent outcomes with reduced morbidity, providing a viable alternative to traditional methods. Conclusion: The cases underscore the critical role of surgical intervention in managing thymic pathologies in MG patients. Both traditional and minimally invasive techniques yield excellent clinical outcomes, reinforcing their importance in the treatment paradigm for thymic hyperplasia and thymoma. Further studies are needed to refine surgical approaches and optimize patient outcomes.

Exploring the clinical significance of anti-acetylcholine receptor antibody titers, changes, and change rates in Myasthenia Gravis

Introduction/AimsMyasthenia Gravis (MG) is a common neuromuscular junction disorder that is primarily mediated by anti-acetylcholine receptor antibodies (AChR-Ab). However, using AChR-Ab titers to predict MG severity and improvement remains controversial. This study aims to explore the relationship between AChR-Ab titers and AChR-Ab rate of change (RR-AChR-Ab, %) and MG scores.MethodsWe used a prospective study approach, and included 62 patients with generalized MG (GMG) who were positive for AChR-Ab. We measured AChR-Ab titers, MGFA-QMGS, and MG-ADL scores at baseline (before treatment) and at 3 and 6 months into treatment. Pearson and Spearman correlation analyses were used to study the relationships between changes in AChR-Ab titers, rates of change, and MG scores.Results(1) At baseline, there was no correlation between AChR-Ab titers and age, duration of illness, gender, MGFA classification, or presence of thymic abnormalities. (2) The trend of decreasing AChR-Ab titers matched the trend of reduced QMGS and ADL scores. (3) Six months into treatment,there was a correlation between AChR-Ab titer changes and changes in ADL scores. (4) Three months into treatment, RR-AChRAb showed a correlation with the rate of change in ADL at the same time point.ConclusionWe found the trend of decreased AChR-Ab titers after standardized treatment that was consistent with reductions in QMGS and ADL scores. Additionally, the rate of change in AChR-Ab titers at 3 months and the change in AChR-Ab titers at 6 months into treatment did reflect improvements in activities of daily living for MG patients.

Ocular Myasthenia gravis: determining the predictive factors of secondary generalisation.

Myasthenia gravis (MG) can be classified according to clinical features into ocular MG (OMG) and generalised MG (GMG). However, OMG carries the risk of conversion to GMG. In this study, we aimed to determine the predictive factors for the secondary generalisation of OMG patients. OMG patients followed-up in our hospital from January 1999 to November 2023 were retrospectively reviewed. Demographic and clinical characteristics data were collected from medical records. OMG patients with follow-up of < 2 years were excluded. Of the 122 patients included, 87 (71.3%) remained as OMG and 35 (28.7%) had converted to GMG. The median time taken for generalisation was 12 months (IQR 6-30). 73.5% of patients had converted to GMG within 2 years. In univariate analysis, a significantly higher proportion of patients with positive anti-AChR antibodies (94.1% vs. 67.1%, p = 0.002), higher antibody titre (8.0 vs. 1.6 nmol/L, p < 0.001), positive repetitive nerve stimulation (RNS) (54.5% vs. 15.9%, p < 0.001), positive single-fibre electromyography (96.7% vs. 76.0%, p = 0.013) and the presence of thymic abnormalities (35.3% vs. 3.5%, p < 0.001), specifically thymoma (29.4% vs. 1.2%, p < 0.001) were associated with secondary generalisation. Conversely, higher percentage of patients who were treated with corticosteroid remained as OMG (37.9% vs. 17.1%, p = 0.026). However, in multivariate analysis, only positive anti-AChR antibodies (ORadj 9.6, 95% CI 1.7-56.1), positive RNS (ORadj 4.0, 95% CI 1.3-12.5) and the presence of thymoma (ORadj 29.5, 95% CI 2.5-351.1) were independently associated with secondary generalisation. The presence of anti-AChR antibodies and thymoma with positive RNS were the predictive factors of secondary generalisation in OMG.

Non-coding RNA and its network in the pathogenesis of Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic autoimmune disease that primarily affects the neuromuscular junction, leading to muscle weakness in patients with this condition. Previous studies have identified several dysfunctions in thymus and peripheral blood mononuclear cells (PBMCs), such as the formation of ectopic germinal centers in the thymus and an imbalance of peripheral T helper cells and regulatory T cells, that contribute to the initiation and development of MG. Recent evidences suggest that noncoding RNA, including miRNA, lncRNA and circRNA may play a significant role in MG progression. Additionally, the network between these noncoding RNAs, such as the competing endogenous RNA regulatory network, has been found to be involved in MG progression. In this review, we summarized the roles of miRNA, lncRNA, and circRNA, highlighted their potential application as biomarkers in diagnosing MG, and discussed their potential regulatory networks in the abnormal thymus and PBMCs during MG development.

Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma

Myasthenia gravis (MG) is etiologically associated with thymus abnormalities, but its pathology in the thymus remains unclear. In this study, we attempt to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We find that the majority of thymomas are constituted by the cortical region. However, the small medullary region is enlarged in seropositive thymomas and contains polygenic enrichment and MG-specific germinal center structures. Neuromuscular medullary thymic epithelial cells, previously identified as MG-specific autoantigen-producing cells, are enriched in the cortico-medullary junction. The medulla is characterized by a specific chemokine pattern and immune cell composition, including migratory dendritic cells and effector regulatory Tcells. Similar germinal center structures and immune microenvironments are also observed in the thymic hyperplasia medulla. This study shows that the medulla and junction areas are linked to MG pathology and provides insights into future MG research.

Advances in Understanding and Managing Myasthenia Gravis: Current Trends and Future Directions.

Myasthenia gravis (MG) is an autoimmune illness characterized by autoantibodies against the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), and an increasing number of extra postsynaptic proteins. Pathogenic autoantibodies reduce the number of functional AChRs in the neuromuscular junction's (NMJ)muscle end plate. The cause of the autoimmune response is unknown, but thymic abnormalities and immune regulatory deficiencies are significant. The disease's incidence is likely influenced by genetic predisposition, with sex hormones and exercise playing a role. MGcan affect any age, race, or gender and can be caused by any stressor, with infections being the most frequent cause. Treatment focuses on airway support and the triggering incident. MG is a rare autoimmune disease causing fatigue-inducing weakness in the axial, respiratory, leg, and bulbar muscles. Initially affecting the eyes, most MGpatients experience at least one worsening symptom during their illness. The disease is mainly caused by antibodies against the AChR, dependence on the immune system within cells, and engagement of the complement system. The complement system plays a significant role in MG, and complement inhibition can both prevent the onset and slow its development. Ocular MG affects around 15% of people, with most patients having blocking antibodies against the cholinergic receptor. There may be correlations between thymoma and other autoimmune conditions, especially thyroid illness. Treatment and management for MGinvolve removing autoantibodies from circulation or blocking effector mechanisms using techniques such as complement inhibition, plasmapheresis, and B-cell elimination.

Clinical Features and Prognostic Analysis of MuSK-Antibody-Positive Myasthenia Gravis versus Double-Seropositive Myasthenia Gravis: A Single-Center Study from Central South China.

To decipher the discrepancies between muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) and double-seropositive myasthenia gravis (DSP-MG), and to determine prognostic factors for minimal manifestation status (MMS) achievement in MG patients with MuSK autoantibodies (MuSK-Ab). A total of 34 MG patients seropositive for MuSK-Ab were enrolled in this study. The demographic and clinical features were compared between MuSK-MG (n = 28) and DSP-MG (n = 6) patients, and factors affecting MMS induction in all patients with MuSK-Ab were identified using Cox regression analysis. Compared to MuSK-MG patients, those with DSP-MG had similar clinical characteristics, except that they had a lower frequency of bulbar muscle involvement at nadir (50% vs 92.9%; P = 0.029) and higher proportions of comorbidities with diabetes mellitus (33.3% vs 0%; P = 0.027) and thymic abnormalities (33.3% vs 0%; P = 0.027). Higher MG Activities of Daily Living (MG-ADL) scores (HR = 0.16, 95% CI: 0.037-0.7, P = 0.015) and axial muscle involvement at nadir (HR = 0.39, 95% CI: 0.16-0.94, P = 0.035) were negative prognostic factors for MMS achievement in patients with MuSK-Ab regardless of acetylcholine receptor antibody (AChR-Ab) positivity. Multivariable Cox regression analysis further established higher MG-ADL scores at the nadir (HR = 0.19, 95% CI: 0.04-0.94; P = 0.042) as an independent risk factor for MMS achievement. DSP-MG was comparable to MuSK-MG and could be considered a single entity in our cohort. In all MG patients with MuSK-Ab, a higher MG-ADL score at nadir may herald a lower chance of MMS achievement, with no observed potential effect of AChR-Ab presence.

Clinical Characteristics and Outcomes of Generalized Myasthenia Gravis in Malaysia: A Single-Center Experience.

Myasthenia gravis (MG) is clinically heterogeneous and can be classified into subgroups according to the clinical presentation, antibody status, age at onset, and thymic abnormalities. This study aimed to determine the clinical characteristics and outcomes of generalized MG (GMG) patients based on these subgroups. Medical records of MG patients from 1976 to 2023 were reviewed retrospectively. Patients with pure ocular MG were excluded. Data on demographic, clinical characteristics, laboratory features, and outcomes were analyzed. This study included 120 GMG patients. There was a slight preponderance of female patients over male patients (male:female ratio=1:1.3), with the age at onset exhibiting a bimodal distribution. Female patients peaked at a lower age (21-30 years) whereas male patients peaked at a higher age (61-70 years). Most (92%, 105 of 114) patients had positive anti-acetylcholine receptor antibodies. Five patients were also tested for anti-muscle-specific tyrosine kinase antibodies, with two showing positivity. Thymectomy was performed in 62 (52%) patients, of which 30 had thymoma, 16 had thymic hyperplasia, 7 had an involuted thymus, and 6 had a normal thymus. There were significantly more female patients (68% vs. 45%, p=0.011) with early-onset disease (<50 years old) and thymic hyperplasia (33% vs. 0%, p<0.025). Most (71%) of the patients had a good outcome based on the Myasthenia Gravis Foundation of America postintervention status. GMG patients with early-onset disease had a significantly better outcome than patients with a late onset in univariate (58% vs. 37%, p=0.041) and multivariate (odds ratio=4.68, 95% confidence interval=1.17-18.64, p=0.029) analyses. Female patients with early-onset MG and thymic hyperplasia had significantly better outcomes, but only early-onset disease was independently associated with a good outcome. These findings are comparable with those of other studies.

Unveiling Myasthenia Gravis: A Comprehensive Analysis of Diagnostic Tools and Clinical Insights

Objective: This research offers a comprehensive analysis of Myasthenia Gravis (MG), uncovering the remarkable accuracy of spinal accessory, ulnar, and facial nerve repetitive nerve stimulation (RNS), along with the precision of single fiber electromyography (SF-EMG) in MG diagnosis. We also embark on an exploration of clinical features and autoantibody test results in generalized MG patients.&#x0D; Methods: In this prospective study, we welcomed 31 individuals definitively diagnosed with generalized MG into our quest. The categorization of patients was conducted in accordance with the criteria set by the Myasthenia Gravis Foundation of America (MGFA). We examined patients' trapezius, nasalis, and abductor digiti minimi (ADM) muscles using RNS. We meticulously recorded the presence of MG autoantibodies, clinical subtypes based on affected muscle groups, and SF-EMG jitter rates.&#x0D; Results: The mean age of the 31 patients of whom 19 (61.3%) were male, was 64 ± 13.9 years. Among them, 20 showed positivity in the Anti-AChR antibody test. In 28 patients, accounting for 90.3% of the study group, single fiber electromyography (EMG) displayed increased jitter. There were 4 (12.9%), 24 (77.4%) and 12 (38.7%) patients featuring a decremental response of exceeding 10% in ADM, trapezius and nasalis muscles, respectivelyOur investigation revealed notable findings, such as the absence of substantial correlations between decremental response rates and age, gender, duration of complaints, antibody test results, thymus abnormalities, affected muscle types, familial history, or increased jitter rates in SF-EMG (p&gt;0.05).&#x0D; Conclusion: As our findings clearly show, we can confidently attest to the remarkable sensitivity of RNS in MG diagnosis when muscle selection is precise. A gem discovered on our study is the high sensitivity of the spinal accessory nerve, a revelation that should guide the course of routine RNS studies, particularly for those facing ocular-onset myasthenia.

Altered serum levels of cytokines in patients with myasthenia gravis

BackgroundMyasthenia gravis (MG) is an autoimmune disease characterized by generalized skeletal muscle contraction weakness due to autoantibodies targeting neural-muscular junctions. Here, we investigated the relationship between key cytokines and MG type, disease course, antibodies, and comorbidities. MethodCytokine levels in serum samples collected from MG (n = 45) and healthy control (HC, n = 38) patients from January 2020 to June 2022 were quantified via flow cytometry. ResultsLevels of IL-6 were higher in the MG group versus healthy individuals (p = 0.026) and in patients with generalized versus ocular MG (p = 0.019). IL-6 levels were positively correlated with QMG score. In patients with MG with both AChR and Titin antibodies, serum levels of sFas and granulysin were higher than in those with AChR alone (p = 0.036, and p = 0.028, respectively). LOMG had a reduction in serum levels of IL-2 compared to EOMG (p = 0.036). LOMG patients with diabetes had lower serum levels of IL-2, IL-4, and IFN-γ (p = 0.044, p = 0.038, and p = 0.047, respectively) versus those without diabetes. sFas in the MG with Abnormal thymus were reduced compared to those in MG with Normal thymus (p = 0.008). ConclusionsThis study revealed a positive correlation between IL-6 level and MG status. Serum cytokine levels of the AChR + Titin MG group differed from those of the AChR group. LOMG had a lower IL-2 level. Comorbidities affect some cytokines in peripheral blood in MG serum.

Review of Teratogenic Effects of Leflunomide, Accutane, Thalidomide, Warfarin, Tetracycline, and Angiotensin-Converting Enzyme Inhibitors.

Teratogenic agents have been shown to have drastic and detrimental effects on fetuses if exposed to the agent during uterine life. The most sensitive time for a developing fetus is during the first trimester, and teratogenic exposure during this time can lead to severe deformities in the fetus. The Food and Drug Administration has categorized teratogenic agents based on the severity of their effecton the fetus; these categories include A, B, C, D, and X. Category A is the safest, with the most dangerous, and highly contraindicated in pregnant patients being Category X. This review article will discuss the teratogenic agents leflunomide, isotretinoin, thalidomide, warfarin, tetracycline, and angiotensinogen-converting enzyme inhibitors. Leflunomide can cause cranioschisis, exencephaly, and vertebral, head, and limb malformations. Isotretinoin's main teratogenic effects include central nervous system malformations, hydrocephalus, eye abnormalities, cardiac septal defects, thymus abnormalities, spontaneous abortions, and external ear abnormalities. Thalidomide has been shown to cause limb deformities, bowel atresia, and heart defects when the embryo is exposed to the agent during development.Warfarin can lead to spontaneous abortion and intrauterine death, as well as nasal hypoplasia, hypoplasia of extremities, cardiac defects, scoliosis, and mental retardation when exposed in utero. Tetracycline's teratogenic effects include gastrointestinal distress, esophageal ulceration and strictures, teeth discoloration, hepatotoxicity, and calcifications. Angiotensinogen-converting enzyme inhibitors can cause skull hyperplasia, anuria, hypotension, renal failure, lung hypoplasia, skeletal deformation, oligohydramnios, and fetal death. Teratogenic effects can be avoided if the pregnant patient is educated on the teratogenic effects of these agents.

Multidetector computed tomography evaluation of normal thymus and variations with age.

Thymus is a T-cell-producing lymphoid organ that appears prominent in the paediatric population and involutes in size with ageing. The gland shows a wide variety of appearances across different age groups. The purpose of the study is to evaluate the computed tomography (CT) appearance of thymus gland in the normal population with a focus on size, CT attenuation and fatty infiltration in different age groups. This is a retrospective study done after taking approval from the Institutional Ethics Committee. Patients undergone CT scans of the thorax were identified from our database. All evaluations were done in non-contrast CT scans. Patients having underlying diseases that may have associated thymic abnormality were excluded. The appearance of thymus and the presence of fatty replacement were assessed. The size of thymus (length and thickness of right limb and left limb) and non-contrast CT Hounsfield unit (HU) value of thymic tissue were measured and compared in various age groups. Four hundred and fifty patients were included, 262 (58.2%) were male. Mean age was 33.6 ± 17.1 years, range (3 months-80 years). The size of thymus was observed to decrease with increasing age. The mean age of complete fatty replacement in our study was 45 years. Complete fatty replacement was noted in all cases with an age of more than 60 years. The most common shape was arrowhead, and the most common location was pre-aortic and para-aortic location. Non-contrast CT HU value was maximum in infants and gradually decreased with advancing age. Even normal thymus can show varied appearance on CT which changes with the age of the patient being imaged. A comparison with normative data could help differentiate normal from abnormal glands to avoid unnecessary intervention.

Delayed-onset adenosine deaminase deficiency with a novel synonymous mutation and a case series from China.

Adenosine deaminase (ADA) is a key enzyme in the purine salvage pathway. Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency. To date, few Chinese cases have been reported. We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature. Nine patients were identified with two novel mutations (W272X and Q202 =). Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients. The ADA genotype has a major effect on the clinical phenotype. Notably, a novel synonymous mutation (c.606G>A, p.Q202=) was identified in a delayed-onset patient, which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein. Furthermore, the patient showed γδT cells expansion with an increased effect or phenotype, which may be associated with the delayed onset of disease. In addition, we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency. Five patients died with a median age of four months, while two patients received stem cell transplantation and are alive. This study described the first case series of Chinese ADA-deficient patients. Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations in our patients. We identified a synonymous mutation that affected pre-mRNA splicing in the ADA gene, which had never been reported in ADA deficiency. Furthermore, we reported cerebral aneurysm in a delayed-onset patient for the first time. Further study is warranted to investigate the underlying mechanisms.

Myasthenia gravis with achalasia secondary to thymoma: a case report and literature review

BackgroundMyasthenia gravis is an autoimmune neuromuscular junction disorder characterized by fatigable muscle weakness and autoantibodies. Frequent associations exist between myasthenia gravis and thymic abnormalities, including hyperplasia and thymoma. Several autoimmune illnesses have been identified to be associated with thymoma; however, a few case reports have linked thymoma and achalasia, and the underlying mechanism is unknown.Case reportA 43-year-old man with thymoma-associated myasthenia gravis presented with dysphagia that was refractory to conventional treatment of myasthenia gravis. This dysphagia was challenging to diagnose even after multiple gastroenterology consults and upper endoscopy. The diagnosis of achalasia type II was established after a comprehensive evaluation, including upper endoscopy, barium swallow, and high-resolution esophageal manometry. The patient underwent elective pneumatic balloon dilatation, which successfully alleviated his dysphagia.ConclusionThis case confirmed the association between myasthenia gravis secondary to thymoma and achalasia and showed how the diagnosis of achalasia was challenging. Awareness of this association is crucial for early diagnosis and treatment, improving affected patients’ quality of life.

Epidemiological study of myasthenia gravis in Japan

AbstractMyasthenia gravis (MG) is an autoimmune‐mediated neurological disorder. The relationship between MG and thymic abnormalities is well recognized, and thymectomy is one of the therapies for anti‐acetylcholine receptor antibody‐positive MG. The major pathogenic factor is anti‐acetylcholine receptor antibody followed by anti‐muscle‐specific kinase antibody, and commercial kits are available to detect these antibodies. Several decades ago, the prognosis of MG was not favorable; therefore, the Ministry of Health and Welfare (predecessor of the Ministry of Health, Labor and Welfare) organized a Taskforce for Intractable Diseases, which included MG, in 1972. The Taskforce carried out consecutive epidemiological studies for MG in 1973, 1987, 2006 and 2018. The four studies found: (i) increasing prevalence; (ii) increasing late‐ and elderly‐onset; (iii) decreasing female dominancy; (iv) decreasing infantile‐onset (onset age of 0–4 years); and (v) decreasing frequencies of crisis. The latest epidemiological study in Japan and studies from other countries suggest an increasing number of patients with anti‐acetylcholine receptor antibody‐positive MG without thymoma in the elderly. It is important to find out the causes of this phenomenon, which will improve the prevention of MG.

Impact of Bifidobacterium longum NSP001 on DSS-induced colitis in conventional and humanised mice

Most scientific investigations regarding inflammatory bowel disease (IBD) pathogenesis or therapeutic strategies use dextran sulfate sodium (DSS)-induced models performed on mice. However, differences between human and animal microbiota may confound the data reproducibility from rodent experiments to clinical trials. In this study, the intervention effects of Bifidobacterium longum NSP001 on DSS-induced colitis were investigated using mice colonized with either native or humanised microbiota. Disorders in disease activity index (DAI), morphology and histology of colon tissue, intestinal permeability, and secretion of MPO, TNF-α and IL-6 were ameliorated by daily intake of live B. longum NSP001 cells in both conventional and humanised colitis mice. But the abnormal thymus index, and colonic production of ZO-1 and iNOS were improved only in colitis mice treated with B. longum NSP001 and humanised microbiome. The accumulation of acetic acid and propionic acid in colon microbiome, and the optimization of primary bile acid biosynthesis and glycerophospholipid metabolism pathways in cecum commensals were likely to explain the beneficial effects of B. longum NSP001. These data revealed that intestinal microbiome baseline would possibly affect the manifestation features of interventions by probiotics or dietary components and highlighted the necessity to include humanised microbiome while investigating potential therapeutic strategies based on rodent models.

Morphologic Changes in the Thymus Following Chemotherapy for Anterior Mediastinal Germ Cell Tumors: A Study of 91 Cases Emphasizing Pseudoneoplastic Features.

The interpretation of postchemotherapy resections of anterior mediastinal germ cell tumors plays a critical role in determining future patient management and prognosis. Treatment-related changes in the thymus may mimic residual teratoma or microcystic-pattern yolk sac tumor. There is limited extant information concerning therapy-related pseudoneoplastic thymic alterations. To provide diagnostic assistance to distinguish nonneoplastic thymic abnormalities secondary to chemotherapy from residual germ cell tumor. We retrospectively reviewed 91 resections of primary anterior mediastinal germ cell tumors with recognizable thymic gland following cisplatin-based chemotherapy. The cohort included 90 men and 1 woman (median age, 29 years). A spectrum of thymic epithelial alterations occurred, including cystic change (macrocysts [n = 21] or microcysts [n = 20]); hyperplasia with reactive atypia (n = 8); ciliated, mucinous, or columnar cell metaplasia (n = 3); and mature squamous metaplasia (n = 2). These changes were similar to so-called acquired multilocular thymic cysts, were often contiguous with and adjacent to normal thymic epithelium, and lacked the neoplastic-type atypia seen in teratomatous elements in this setting. In 1 case, confluent microcysts closely mimicked the appearance of yolk sac tumor but lacked other distinctive features of that neoplasm and its characteristic immunoreactivity. Recognition of therapy-induced thymic changes is important to avoid misinterpretation as residual teratoma or yolk sac tumor. Continuity with and proximity to benign thymic epithelium, absence of neoplastic-type atypia, and awareness of this phenomenon are important in avoiding this pitfall.

Autoimmunity to acetylcholine receptor channels

AbstractAnti‐acetylcholine receptor antibody (AChRAb) targets nicotinic acetylcholine receptors (AChRs) of the neuromuscular junction (NMJ). AChRAb induces degradation of AChRs, which causes a decrease in the efficacy of neuromuscular transmission. The clinical condition induced by this process is myasthenia gravis (MG). Transmission failure at the NMJ is detectable by a repetitive nerve stimulation test. AChRAb may be complicated with thymic abnormalities (thymoma and/or lymphoreticular hyperplasia [LFH]). Moreover, autoimmune thyroid disease may accompany MG. Thymoma and LFH have etiological roles in AChRAb production, and the removal of thymoma and LFH improve MG symptoms. MG therapies, such as acetylcholine esterase inhibitor (AChEI), aim to increase the efficacy of NMJ transmission; however, the effect of AChEI is limited. The primary therapy aims to decrease AChRAb and is combined with thymectomy. There are two methods to remove AChRAb from the patients' blood: (1) reduce the production of immunoglobulins by administration of corticosteroid and/or immunosuppressants and (2) remove immunoglobulin by blood purification. In some patients, long‐lasting immunosuppression is necessary, which causes adverse events. Combinatory use of other immunosuppressants reduces the adverse events of corticosteroids. In addition, intravenous immunoglobulin is available to modify the proportion of immunoglobulin in patients' blood. Recently, humanized monoclonal antibodies against specific molecules have been introduced for immunoglobulin modification; however, they are not AChRAb specific. Thus, it is necessary to consider the safety and cost‐effectiveness of therapies.

Can MRI chemical shift imaging replace thymic biopsy in myasthenia gravis patients?

BackgroundMyasthenia gravis is a neuromuscular junction autoimmune condition characterized by muscle weakness. Many people with myasthenia gravis have thymic abnormalities, such as thymic lymphoid hyperplasia and thymic tumors, therefore, the thymus plays a significant role in the disease. The imaging properties of thymic hyperplasia and thymoma on CT and conventional MRI are very similar, yet, MRI has recently revealed promising capability by adding novel sequences. Chemical shift MRI was demonstrated to consistently distinguish thymic hyperplasia from thymus gland tumors. The aim of this study was to determine the value of chemical shift MRI imaging in characterizing thymic lesions in patients diagnosed with myasthenia gravis and its ability to differentiate thymic hyperplasia from thymoma.ResultsMRI showed that thymic lymphoid hyperplasia was more common to be convex in shape while thymoma was more likely to be round or irregular (P = 0.004). Paired comparison between histopathology and chemical shift MRI showed that MRI had 90% sensitivity and 100% specificity in detecting thymoma with overall diagnostic accuracy 93.3% (P = 0.5). MRI chemical shift ratio showed 100% sensitivity by using > 0.85 as a cut off value for diagnosis of thymoma, with specificity 83.3% (P = 0.0001). There was statistically significant difference in chemical shift ratio between thymic lymphoid hyperplasia and thymoma groups, as thymoma group had a higher chemical shift ratio of 1.06 ± 0.06 compared to 0.48 ± 0.13 in thymic hyperplasia group (P = 0.0001).ConclusionMRI chemical shift imaging with chemical shift ratio offers a highly sensitive and specific tool in assessment of thymus lesions in myasthenia gravis patients and it can differentiate between thymic hyperplasia and thymoma using cutoff value of > 0.85, hence, unwarranted invasive procedures as thymic biopsy or thymectomy can be avoided and proper management could be planned.

Insufficiency of CD205-positive cortical thymic epithelial cells in immature Japanese Black cattle with severe thymic abnormalities and poor prognosis

To investigate the involvement of thymic function in the development of diseases with poor prognosis in calves, this study conducted a survey for the assessment of thymus cell composition in immature Japanese Black cattle with poor prognosis. Histopathological evaluation of 47 cattle showed signs of acute thymic involution in most cases. Less than half of the cases had a cortex predominant over the medulla in the thymic parenchyma, and a quarter of the cases indicated severe histological condition with an unclear boundary between the cortex and medulla. Correlation analysis revealed a close relationship between the corresponding stages of acute involution, cortical occupancy, and the expression of CD4, CD8B, and CD205. When cases were grouped by cortical occupancy, the expression of CD4 and CD8B expression was lower in the severe group with less than 25 % cortical occupancy, and the expression of CD205 was lower in the group with an unclear cortical-medullary boundary. Meanwhile, there was no difference in the expressions of IL7, CD80, FEZF2, and FOXN1 according to cortical occupancy. Immunohistochemistry has shown that cytokeratin-positive thymic epithelial cells are more densely populated in the severe thymus. UEA-I-binding medullary thymic epithelial cells were also present, but CD205-positive cortical thymic epithelial cells were rare in severe thymus. Moreover, there were significantly fewer Ki-67-positive cells in cattle with severe thymus. Therefore, these results indicate that thymic histological abnormalities frequently occur in immature cattle with a poor prognosis, and the presence of CD205-positive cortical thymic epithelial cells is associated with the severity of the abnormalities.