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Journal of Clinical Immunology Jul 2024Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described...
BACKGROUND
Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome.
OBJECTIVES
To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation.
METHODS
Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab.
RESULTS
Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12-36 months following treatment initiation.
CONCLUSION
Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma.
Topics: Humans; Thymoma; Female; Immunomodulation; Male; Rituximab; Autoantibodies; Middle Aged; Thymus Neoplasms; Pneumonia; Autoimmune Diseases; Adult; Azathioprine; B-Lymphocytes; Treatment Outcome; T-Lymphocytes
PubMed: 38954150
DOI: 10.1007/s10875-024-01760-3 -
Abdominal Radiology (New York) Jul 2024Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some... (Review)
Review
Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some etiologies, such as primary sclerosing cholangitis, primary biliary cholangitis, and ischemic cholangitis, often have distinctive imaging findings. In contrast, other causes such as chronic rejection following liver transplantation, drug-induced biliary injury, infection, malignancy such as lymphoma, and graft-versus-host disease may only have ancillary or non-specific imaging findings. Thus, diagnosing ductopenia in conditions with nonspecific imaging findings requires a multidimensional approach, including clinical evaluation, serological testing, imaging, and liver histology to identify the underlying cause. These etiologies lead to impaired bile flow, resulting in cholestasis, liver dysfunction, and, ultimately, cirrhosis and liver failure if the underlying cause remains untreated or undetected. In the majority of instances, individuals diagnosed with ductopenia exhibit a positive response to treatment addressing the root cause or cessation of the causative agent. This article focuses on acquired causes of ductopenia, its clinical manifestation, histopathology, imaging diagnosis, and management.
PubMed: 38954003
DOI: 10.1007/s00261-024-04462-x -
Der Nervenarzt Jul 2024Neurodegenerative diseases represent an increasing challenge in ageing societies, as only limited treatment options are currently available. (Review)
Review
BACKGROUND
Neurodegenerative diseases represent an increasing challenge in ageing societies, as only limited treatment options are currently available.
OBJECTIVE
New research methods and interdisciplinary interaction of different disciplines have changed the way neurological disorders are viewed and paved the way for the comparatively new field of neuroimmunology, which was established in the early 1980s. Starting from neurological autoimmune diseases, such as multiple sclerosis, knowledge about the involvement of immunological processes in other contexts, such as stroke or traumatic brain injury, has been significantly expanded in recent years.
MATERIAL AND METHODS
This review article provides an overview of the role of the immune system and the resulting potential for novel treatment approaches.
RESULTS
The immune system plays a central role in fighting infections but is also able to react to the body's own signals under sterile conditions and cause inflammation and subsequent adaptive immune responses through the release of immune mediators and the recruitment and differentiation of certain immune cell types. This can be beneficial in initiating healing processes; however, chronic inflammatory conditions usually have destructive consequences for the tissue and the organism and must be interrupted.
CONCLUSION
It is now known that different cells of the immune system play an important role in neurological diseases. Regulatory mechanisms, which are mediated by regulatory T cells or Th2 cells, are usually associated with a good prognosis, whereas inflammatory processes and polarization towards Th1 or Th17 have a destructive character. Novel immunomodulators, which are also increasingly being used in cancer treatment, can now be used in a tissue-specific manner and therefore offer great potential for use in neurological diseases.
PubMed: 38953921
DOI: 10.1007/s00115-024-01696-4 -
Molecular Pharmaceutics Jul 2024The coronavirus (COVID-19) pandemic has underscored the critical role of mRNA-based vaccines as powerful, adaptable, readily manufacturable, and safe methodologies for... (Review)
Review
The coronavirus (COVID-19) pandemic has underscored the critical role of mRNA-based vaccines as powerful, adaptable, readily manufacturable, and safe methodologies for prophylaxis. mRNA-based treatments are emerging as a hopeful avenue for a plethora of conditions, encompassing infectious diseases, cancer, autoimmune diseases, genetic diseases, and rare disorders. Nonetheless, the in vivo delivery of mRNA faces challenges due to its instability, suboptimal delivery, and potential for triggering undesired immune reactions. In this context, the development of effective drug delivery systems, particularly nanoparticles (NPs), is paramount. Tailored with biophysical and chemical properties and susceptible to surface customization, these NPs have demonstrated enhanced mRNA delivery in vivo and led to the approval of several NPs-based formulations for clinical use. Despite these advancements, the necessity for developing a refined, targeted NP delivery system remains imperative. This review comprehensively surveys the biological, translational, and clinical progress in NPs-mediated mRNA therapeutics for both the prevention and treatment of diverse diseases. By addressing critical factors for enhancing existing methodologies, it aims to inform the future development of precise and efficacious mRNA-based therapeutic interventions.
PubMed: 38953708
DOI: 10.1021/acs.molpharmaceut.4c00276 -
MBio Jul 2024Polyomaviruses are species-specific DNA viruses that can cause disease in immunocompromised individuals. Despite their role as the causative agents for several diseases,...
UNLABELLED
Polyomaviruses are species-specific DNA viruses that can cause disease in immunocompromised individuals. Despite their role as the causative agents for several diseases, there are no currently approved antivirals for treating polyomavirus infection. Brincidofovir (BCV) is an antiviral approved for the treatment of poxvirus infections and has shown activity against other double-stranded DNA viruses. In this study, we tested the efficacy of BCV against polyomavirus infection and using mouse polyomavirus (MuPyV). BCV inhibited virus production in primary mouse kidney cells and brain cortical cells. BCV treatment of cells transfected with MuPyV genomic DNA resulted in a reduction in virus levels, indicating that viral inhibition occurs post-entry. Although BCV treatment had a limited effect on viral DNA and RNA levels, drug treatment was associated with a reduction in viral protein, raising the possibility that BCV acts post-transcriptionally to inhibit MuPyV infection. In mice, BCV treatment was well tolerated, and prophylactic treatment resulted in a reduction in viral DNA levels and a potent suppression of infectious virus production in the kidney and brain. In mice with chronic polyomavirus infection, therapeutic administration of BCV decreased viremia and reduced infection in the kidney. These data demonstrate that BCV exerts antiviral activity against polyomavirus infection , supporting further investigation into the use of BCV to treat clinical polyomavirus infections.
IMPORTANCE
Widespread in the human population and able to persist asymptomatically for the life of an individual, polyomavirus infections cause a significant disease burden in the immunocompromised. Individuals undergoing immune suppression, such as kidney transplant patients or those treated for autoimmune diseases, are particularly at high risk for polyomavirus-associated diseases. Because no antiviral agent exists for treating polyomavirus infections, management of polyomavirus-associated diseases typically involves reducing or discontinuing immunomodulatory therapy. This can be perilous due to the risk of transplant rejection and the potential development of adverse immune reactions. Thus, there is a pressing need for the development of antivirals targeting polyomaviruses. Here, we investigate the effects of brincidofovir, an FDA-approved antiviral, on polyomavirus infection using mouse polyomavirus. We show that the drug is well-tolerated in mice, reduces infectious viral titers, and limits viral pathology, indicating the potential of brincidofovir as an anti-polyomavirus therapeutic.
PubMed: 38953354
DOI: 10.1128/mbio.01049-24 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024Primary central nervous system vasculitis (PACNS) is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous...
Primary central nervous system vasculitis (PACNS) is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous system,involving the brain,spinal cord,and meninges.Tumor-like PNCAS,a rare subtype of PACNS,is often misdiagnosed as intracranial malignancy,and that with spinal cord involvement is even more uncommon.The lack of specific clinical symptoms and imaging manifestations poses a challenge to the diagnosis of PACNS.This report presents a case of tumor-like PACNS with spinal cord involvement based on the pathological evidence,aiming to enrich the knowledge about this condition.
Topics: Humans; Vasculitis, Central Nervous System; Female; Male; Spinal Cord; Middle Aged
PubMed: 38953273
DOI: 10.3881/j.issn.1000-503X.15762 -
Cureus May 2024Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease characterized by nonspecific symptoms such as fever, maculopapular rash, and arthralgias. The exact...
Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease characterized by nonspecific symptoms such as fever, maculopapular rash, and arthralgias. The exact etiology and pathogenesis remain unclear despite advancements in medical science. Diagnosis is typically established using the Yamaguchi criteria, which include a negative antinuclear antibody (ANA) test as one of the minor criteria. However, some patients with AOSD exhibit positive ANA and even positive antineutrophil cytoplasmic antibodies (ANCA), complicating the diagnostic process. We present the case of a 19-year-old Asian woman of Yakut ethnicity who initially presented with symptoms resembling an upper respiratory tract infection. Laboratory tests revealed the presence of both ANA and ANCA. The diagnosis of AOSD was confirmed based on clinical presentation and the Yamaguchi criteria. Subsequent pulse therapy with prednisolone resulted in significant clinical improvement and a one-year remission. A review of the literature revealed that simultaneous ANCA and ANA positivity in AOSD has not been previously reported. Follow-up over 12 months showed no evidence of other autoimmune or autoinflammatory diseases, suggesting that the positive ANA and ANCA results may be either false positives or atypical laboratory manifestations in AOSD, which should be considered in the diagnosis.
PubMed: 38953085
DOI: 10.7759/cureus.61399 -
Cureus May 2024Celiac disease (CD) is defined as an autoimmune disease (AD) caused by gluten ingestion in genetically sensitive individuals. Several publications have demonstrated the...
INTRODUCTION
Celiac disease (CD) is defined as an autoimmune disease (AD) caused by gluten ingestion in genetically sensitive individuals. Several publications have demonstrated the increased risk of AD in patients with CD, both adults and children, which requires systematic research. Our study aimed to determine the prevalence of AD in 60 patients diagnosed with CD and to highlight risk factors that may contribute to the emergence of AD.
MATERIALS AND METHODS
We collected medical data from all CD patients under 16 years of age who also had AD. Our study was conducted in the Gastroenterology-Hepatology and Pediatric Nutrition Unit of the Pediatrics Department of the Mohamed VI Hospital and University Center in Oujda, Morocco, during a seven-year period between January 2017 and January 2024.
RESULTS
We studied 60 patients with CD in our study. Eight patients (13%) had an associated AD. Their average age was eight years, with extremes varying between two and 15 years. AD was diagnosed before CD in six cases (75%), in parallel with CD in one patient (12.5%), while in only one case, it was diagnosed after CD (12.5%). All our patients had a single AD associated with CD. These ADs were mainly type 1 diabetes in seven cases and autoimmune thyroiditis in only one case. All our patients followed a gluten-free diet in addition to specific treatment for associated AD. Nevertheless, despite regular medical follow-up and targeted dietary advice for the management of CD and associated AD, three patients encountered difficulties in following the recommended diet.
CONCLUSION
Younger patients with CD have an increased risk of hypothyroidism and insulin-dependent diabetes. These data necessitate improved surveillance to discover these illnesses as early as possible in order to optimize management and reduce related consequences.
PubMed: 38953066
DOI: 10.7759/cureus.61468 -
Frontiers in Immunology 2024Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of... (Review)
Review
BACKGROUND AND OBJECTIVES
Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of anti-GlyR antibody-related disease.
METHODS
By collecting clinical information from admitted patients positive for glycine receptor (GlyR) antibody, the clinical characteristics of a new patient positive for GlyR antibody were reported in this study. To obtain additional information regarding anti-GlyR antibody-linked illness, clinical data and findings on both newly reported instances in this study and previously published cases were merged and analyzed.
RESULTS
A new case of anti-GlyR antibody-related progressive encephalomyelitis with rigidity and myoclonus (PERM) was identified in this study. A 20-year-old man with only positive cerebrospinal fluid anti-GlyR antibody had a good prognosis with first-line immunotherapy. The literature review indicated that the common clinical manifestations of anti-GlyR antibody-related disease included PERM or stiff-person syndrome (SPS) (n = 179, 50.1%), epileptic seizure (n = 94, 26.3%), and other neurological disorders (n = 84, 24.5%). Other neurological issues included demyelination, inflammation, cerebellar ataxia and movement disorders, encephalitis, acute psychosis, cognitive impairment or dementia, celiac disease, Parkinson's disease, neuropathic pain and allodynia, steroid-responsive deafness, hemiballism/tics, laryngeal dystonia, and generalized weakness included respiratory muscles. The group of PERM/SPS exhibited a better response to immunotherapy than others.
CONCLUSIONS
The findings suggest the presence of multiple clinical phenotypes in anti-GlyR antibody-related disease. Common clinical phenotypes include PERM, SPS, epileptic seizure, and paraneoplastic disease. Patients with RERM/SPS respond well to immunotherapy.
Topics: Humans; Male; Receptors, Glycine; Autoantibodies; Young Adult; Encephalomyelitis; Muscle Rigidity; Myoclonus; Stiff-Person Syndrome; Adult
PubMed: 38953026
DOI: 10.3389/fimmu.2024.1387591 -
Frontiers in Immunology 2024The predominant characteristic of autoimmune gastritis (AIG) is corpus-dominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are...
The predominant characteristic of autoimmune gastritis (AIG) is corpus-dominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are needed on the endoscopic features of the early stage. In this report, we present two cases of early-stage AIG in which endoscopic examinations showed no atrophy of the gastric mucosa but displayed a transition of collecting venules from a regular to an irregular arrangement. In addition, yellowish-white cobblestone-like elevations were observed in the fundic gland region. Histologically, the observed manifestations included pseudohypertrophy and protrusion of parietal cells into the lumen, possibly along with hyperplasia of G cells, lymphocytic infiltration and potentially pseudopyloric gland metaplasia. Serologically, the anti-parietal cell antibody returned positive results, whereas the anti-intrinsic factor antibody yielded negative results. In this study, we summarized some endoscopic features of two patients, aiming to provide clues for endoscopists to detect early-stage AIG.
Topics: Humans; Autoimmune Diseases; Male; Gastritis; Female; Middle Aged; Autoantibodies; Gastric Mucosa; Parietal Cells, Gastric; Gastroscopy; Biopsy; Aged; Adult
PubMed: 38953024
DOI: 10.3389/fimmu.2024.1416292