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Search Results (102)

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Keywords = p-ANCA

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15 pages, 3293 KiB  
Review
Aggressiveness in Well-Differentiated Small Intestinal Neuroendocrine Tumors: A Rare Case and Narrative Literature Review
by Laurențiu Augustus Barbu, Liviu Vasile, Liliana Cercelaru, Valeriu Șurlin, Stelian-Ștefaniță Mogoantă, Gabriel Florin Răzvan Mogoș, Tiberiu Stefăniță Țenea Cojan, Nicolae-Dragoș Mărgăritescu, Marius P. Iordache and Anca Buliman
J. Clin. Med. 2025, 14(16), 5821; https://doi.org/10.3390/jcm14165821 - 18 Aug 2025
Viewed by 220
Abstract
Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignancies of the small bowel. Although typically well differentiated and slow-growing, they may exhibit aggressive behavior, especially when diagnosed at an advanced stage. Objective: To illustrate the diagnostic and therapeutic challenges of advanced [...] Read more.
Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignancies of the small bowel. Although typically well differentiated and slow-growing, they may exhibit aggressive behavior, especially when diagnosed at an advanced stage. Objective: To illustrate the diagnostic and therapeutic challenges of advanced SI-NETs through a rare case presentation and a narrative review of recent studies in the literature. Methods: A narrative literature review was conducted using the PubMed database to examine the incidence, risk factors, diagnostic modalities, and treatment strategies for advanced-stage SI-NETs. The search included studies published between January 2010 and June 2025 and focused on human subjects, using keywords such as “small intestinal neuroendocrine tumor”, “metastasis”, “tumor grade”, and “treatment”. Results: We report the case of a 68-year-old man who presented with bowel obstruction. Imaging and surgical exploration revealed a jejunoileal SI-NET with extensive liver and peritoneal metastases, mesenteric fibrosis, and ascites. Histopathology confirmed a well-differentiated grade 2 tumor (Ki-67: 3%) positive for chromogranin A and CD56. Despite a low proliferative index, the tumor demonstrated aggressive clinical behavior. The patient underwent emergency enterectomy with ileostomy and was referred for further evaluation, including somatostatin receptor imaging and consideration for peptide receptor radionuclide therapy (PRRT). Conclusions: This case highlights the potential for aggressive progression in well-differentiated SI-NETs with low Ki-67 indices. Histological grade alone may not predict clinical behavior. Early diagnosis, comprehensive staging, and individualized multidisciplinary management—guided by functional imaging and receptor profiling—are critical to improving outcomes in advanced SI-NETs. Full article
(This article belongs to the Special Issue Clinical Advances in Abdominal Surgery)
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21 pages, 3177 KiB  
Review
Immunological and Inflammatory Biomarkers in the Prognosis, Prevention, and Treatment of Ischemic Stroke: A Review of a Decade of Advancement
by Marius P. Iordache, Anca Buliman, Carmen Costea-Firan, Teodor Claudiu Ion Gligore, Ioana Simona Cazacu, Marius Stoian, Doroteea Teoibaș-Şerban, Corneliu-Dan Blendea, Mirela Gabriela-Irina Protosevici, Cristiana Tanase and Maria-Linda Popa
Int. J. Mol. Sci. 2025, 26(16), 7928; https://doi.org/10.3390/ijms26167928 - 16 Aug 2025
Viewed by 385
Abstract
Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, [...] Read more.
Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and chemokines like interleukin-8 (IL-8) rapidly rise, promoting blood–brain barrier disruption, leukocyte infiltration, and neuronal death. Conversely, anti-inflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) facilitate repair, neurogenesis, and immune regulation in later phases. The balance between these pathways determines outcomes and is reflected in circulating biomarkers. Composite hematological indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) offer accessible and cost-effective prognostic tools. Several biomarkers correlate with infarct size, neurological deterioration, and mortality, and may predict complications like hemorrhagic transformation or infection. Therapeutic strategies targeting cytokines, especially IL-1 and IL-6, have shown promise in modulating inflammation and improving outcomes. Future directions include personalized immune profiling, real-time cytokine monitoring, and combining immunotherapy with neurorestorative approaches. By integrating immune biomarkers into stroke care, clinicians may enhance risk stratification, optimize treatment timing, and identify candidates for novel interventions. This review underscores inflammation’s dual role and evolving therapeutic and prognostic relevance in ischemic stroke. Full article
(This article belongs to the Section Molecular Neurobiology)
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12 pages, 2212 KiB  
Case Report
Cocaine-Triggered PR3-ANCA Vasculitis Localized to a Post-Surgical Neck Field: A Case of Locus Minoris Resistentiae in Drug-Induced Autoimmunity
by Marko Tarle, Koraljka Hat, Lea Šalamon, Joško Mitrović, Marina Raguž, Danko Müller and Ivica Lukšić
Diagnostics 2025, 15(16), 1999; https://doi.org/10.3390/diagnostics15161999 - 10 Aug 2025
Viewed by 335
Abstract
Background and Clinical Significance: Cocaine-induced vasculitis (CIV), especially when associated with PR3-ANCA positivity, can be very similar both clinically and serologically to idiopathic granulomatosis with polyangiitis (GPA). The distinction between these entities is crucial due to the different etiologies, treatment strategies, and prognoses. [...] Read more.
Background and Clinical Significance: Cocaine-induced vasculitis (CIV), especially when associated with PR3-ANCA positivity, can be very similar both clinically and serologically to idiopathic granulomatosis with polyangiitis (GPA). The distinction between these entities is crucial due to the different etiologies, treatment strategies, and prognoses. We present a unique case of CIV that manifested exclusively in a previously dissected neck area—an example of the locus minoris resistance phenomenon—and was initially misinterpreted as skin melanoma recurrence. Case presentation: A 59-year-old man with a history of skin melanoma (pT4b, left pectoral region) and a previous modified radical neck dissection presented in 2024 with new onset of painful subcutaneous nodules and ulcerative lesions at the surgical site. The imaging procedures (CT and PET-CT) raised the suspicion of locoregional malignant recurrence. However, histology revealed necrotizing granulomatous inflammation without tumor cells. Extensive infectious and autoimmune investigations ruled out alternative causes. Subsequently, the patient developed a perforation of the nasal septum and ulcers on the oral mucosa. PR3-ANCA was strongly positive (up to 49 U/mL). Urine toxicology revealed intranasal cocaine use. A diagnosis of cocaine-induced PR3-ANCA vasculitis was made. After immunosuppressive therapy (high-dose glucocorticoids and methotrexate) and substance withdrawal counseling, the patient showed significant clinical improvement. Conclusions: This case highlights the importance of including CIV in the differential diagnosis of granulomatous or ulcerative lesions, especially when they are localized to previous surgical sites. The presentation illustrates the concept of locus minoris resistentiae and highlights the role of toxicological testing in atypical ANCA-positive disease. Full article
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10 pages, 269 KiB  
Article
Similarities and Differences Between Patients Diagnosed with ANCA-Associated Vasculitis Who Are Positive and Negative for ANCA: University Clinic Practice and Expertise
by Giedre Dereseviciene, Jolanta Dadoniene and Dalia Miltiniene
Medicina 2025, 61(8), 1369; https://doi.org/10.3390/medicina61081369 - 29 Jul 2025
Viewed by 230
Abstract
Background and objective. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small- to medium-sized vessels and is characterized by the production of ANCAs. The ANCA-negative term is used if the patient otherwise fulfills the definition for AAV but has negative results on serologic testing [...] Read more.
Background and objective. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small- to medium-sized vessels and is characterized by the production of ANCAs. The ANCA-negative term is used if the patient otherwise fulfills the definition for AAV but has negative results on serologic testing for ANCAs. The objective of this study was to compare ANCA-positive and -negative vasculitis patients and to evaluate the main differences possibly related to the presence of ANCAs. Material and methods. A cross-sectional study of 73 patients treated at the tertiary Rheumatology Centre of University Hospital from the 1 January, 2001, to the 31August, 2023, with diagnoses of AAV was carried out. Clinical characteristics and laboratory data were collected at the onset or at the first year of the disease. Results. Forty-eight (65.8%) patients were ANCA-positive, while twenty-five (34.3%) were ANCA-negative. Distribution by gender was similar in both groups, with a female–male ratio of 2:1. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were elevated for all AAV patients, but values were higher in the ANCA-positive patients’ group. The median hemoglobin was 106 g/L in the seropositive group and 127 g/L in the seronegative group. A higher prevalence of kidney involvement (60.4%) with elevated serum creatinine level (93.5 µmol/L) was observed in the ANCA-positive group compared with 24% and 70 µmol/l in the ANCA-negative group (p < 0.05). Neurological involvement was more frequently found in the ANCA-positive patient group, too: 29.2% compared to 20%. Among patients with ANCA-negative vasculitis, 88% had pulmonary; 92% ear, nose, throat (ENT); 48% joint; and 28% skin presentation. In comparison, involvement of these organs was less common in the ANCA-positive patients’ group, at 79.2%, 60.4%, 31.3%, and 25 %, respectively. Conclusions. ANCA-positive patients appear to be in a more difficult clinical situation in terms of organ involvement and laboratory changes. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases: 2nd Edition)
18 pages, 770 KiB  
Article
Evaluation of Nailfold Capillaroscopy as a Novel Tool in the Assessment of Eosinophilic Granulomatosis with Polyangiitis
by Gianluca Screm, Ilaria Gandin, Lucrezia Mondini, Rossella Cifaldi, Paola Confalonieri, Chiara Bozzi, Francesco Salton, Giulia Bandini, Giorgio Monteleone, Michael Hughes, Paolo Cameli, Marileda Novello, Rossana Della Porta, Geri Pietro, Marco Confalonieri and Barbara Ruaro
J. Clin. Med. 2025, 14(15), 5311; https://doi.org/10.3390/jcm14155311 - 28 Jul 2025
Viewed by 337
Abstract
Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), represent a spectrum of systemic disorders characterized by necrotizing inflammation of small- to medium-sized vessels. Nailfold videocapillaroscopy (NVC) is a validated, non-invasive [...] Read more.
Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), represent a spectrum of systemic disorders characterized by necrotizing inflammation of small- to medium-sized vessels. Nailfold videocapillaroscopy (NVC) is a validated, non-invasive technique routinely employed in the assessment of microvascular involvement in systemic sclerosis and in the differential diagnosis of Raynaud’s phenomenon; its application in the context of AAV, particularly EGPA, has not been investigated yet. The present study aims to assess the presence and the possible pattern of microcirculatory abnormalities detected by NVC in EGPA patients, and to explore potential correlations between capillaroscopic findings and disease activity status. Methods: A total of 29 patients with EGPA (19 women and 10 men), aged between 51 and 73 years, and 29 age- and sex-matched healthy controls were retrospectively enrolled between October 2023 and April 2025, after providing informed consent and meeting the inclusion and exclusion criteria. NVC was conducted in both groups to assess various morphological parameters, and mean capillary density was also calculated. Results: This study observed the presence of capillaroscopic alterations in the EGPA group, including decreased capillary density (38%), neoangiogenesis (72%), rolling (100%), pericapillary stippling (66%), and inverted capillary apex (52%). Overall, when comparing healthy controls with EGPA patients, microcirculatory abnormalities were significantly more prevalent in the latter. Specifically, scores for neoangiogenesis, capillary rolling, pericapillary stippling, and inverted capillary apex showed p-values < 0.001. Conclusions: Our study demonstrates a higher prevalence of four nailfold videocapillaroscopic abnormalities in patients with EGPA compared to healthy controls. However, the identification of these capillaroscopic alterations as specific to EGPA requires further confirmation. Ongoing studies aim to explore the potential role of NVC as a diagnostic marker and to investigate its correlation with the clinical manifestations of EGPA. Full article
(This article belongs to the Special Issue Clinical Advances in Autoimmune Disorders)
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12 pages, 452 KiB  
Article
Association Between Hearing Loss and Systemic Small-Vessel Vasculitis: Audiological Aspects Across Disease Types
by Vija Vainutienė, Eugenijus Lesinskas, Tatjana Ivaškienė, Diana Mieliauskaitė, Jolanta Dadonienė, Dalia Miltinienė and Justinas Ivaška
Medicina 2025, 61(7), 1117; https://doi.org/10.3390/medicina61071117 - 20 Jun 2025
Viewed by 429
Abstract
Background and Objectives: Systemic small-vessel vasculitis (SV) represents a group of rare autoimmune disorders with varied etiologies and clinical manifestations. Audiovestibular involvement in SV may present with a broad spectrum of symptoms, often complicating diagnosis and management. This study aimed to evaluate [...] Read more.
Background and Objectives: Systemic small-vessel vasculitis (SV) represents a group of rare autoimmune disorders with varied etiologies and clinical manifestations. Audiovestibular involvement in SV may present with a broad spectrum of symptoms, often complicating diagnosis and management. This study aimed to evaluate auditory function and speech perception in individuals diagnosed with SV and to investigate associations with disease-specific clinical parameters. Materials and Methods: A total of 40 patients diagnosed with SV (mean age: 48.9 years; range: 28–65 years) were recruited for comprehensive audiological assessment. The evaluation protocol included otoscopic examination, tympanometry, pure-tone audiometry, and speech audiometry. Statistical analysis was conducted using R software (version 4.3.1), and significance was set at p < 0.05. Results: Diagnoses included granulomatosis with polyangiitis (52.5%), eosinophilic granulomatosis with polyangiitis (27.5%), necrotizing vasculopathy (12.5%), and microscopic polyangiitis (7.5%). Mean disease duration was 4.14 years. Hearing complaints were reported by 77.5%; in 20%, they were the initial symptoms. Audiometry identified hearing loss in 50% of patients—predominantly sensorineural (33.8%), followed by mixed (13.7%) and conductive (2.5%) types. Hearing loss was most frequent in necrotizing vasculopathy (60%) and among ANCA-positive individuals (53.7%). Conclusions: Sensorineural hearing loss is common in SV, particularly in ANCA-positive patients, highlighting the need for routine hearing assessment in SV management. Full article
(This article belongs to the Section Hematology and Immunology)
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13 pages, 825 KiB  
Article
Impact of Early MPO-ANCA Positivity on Unique Clinical Features in Korean Patients with EGPA: A Single-Centre Cohort Study
by Oh Chan Kwon, Jang Woo Ha, Min-Chan Park, Yong-Beom Park and Sang-Won Lee
Medicina 2025, 61(6), 1088; https://doi.org/10.3390/medicina61061088 - 13 Jun 2025
Cited by 1 | Viewed by 563
Abstract
Objectives: Previous studies have suggested differences in vasculitic and eosinophilic phenotypes based on anti-neutrophil cytoplasmic antibody (ANCA) positivity in eosinophilic granulomatosis with polyangiitis (EGPA). However, their relevance under the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification [...] Read more.
Objectives: Previous studies have suggested differences in vasculitic and eosinophilic phenotypes based on anti-neutrophil cytoplasmic antibody (ANCA) positivity in eosinophilic granulomatosis with polyangiitis (EGPA). However, their relevance under the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria remains unclear. We aimed to evaluate the clinical features and outcomes of EGPA according to myeloperoxidase (MPO)-ANCA status in a Korean cohort. Methods: We conducted a retrospective cohort study that included 57 patients with EGPA without proteinase 3-ANCA positivity who fulfilled the 2022 ACR/EULAR classification criteria. Patients were classified into MPO-ANCA-positive (n = 25) and MPO-ANCA-negative (n = 32) groups. Clinical manifestations, laboratory findings, and outcomes, including all-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident (CVA), and acute coronary syndrome (ACS), were compared between the two groups. Results: MPO-ANCA-positive patients exhibited higher Five-Factor Scores (1.0 [0.0–1.0] vs. 0.0 [0.0–1.0], p = 0.038), lower Short Form 36 Physical Component Summary scores (35.0 [19.7–56.3] vs. 52.5 [43.5–69.7], p = 0.048), and elevated systemic inflammation markers (higher erythrocyte sedimentation rate: 58.0 [16.0–97.5] mm/hr vs. 25.5 [7.0–63.8] mm/hr, p = 0.026). Constitutional symptoms were more frequent among MPO-ANCA-positive patients (n = 14 [56.0%] vs. n = 3 [9.4%], p < 0.001), whereas no significant differences were found in vasculitic or eosinophilic manifestations. Kaplan–Meier analysis revealed no differences in the overall (p = 0.36), relapse-free (p = 0.80), ESKD-free (p = 0.87), CVA-free (p = 0.26), or ACS-free (p = 0.94) survival rates between the two groups. Conclusions: In Korean patients with EGPA classified under the 2022 ACR/EULAR classification criteria, MPO-ANCA positivity, as compared to ANCA-negative status, was associated with a higher disease burden and poorer quality of life but not with distinct vasculitic or eosinophilic manifestations and adverse outcomes. Full article
(This article belongs to the Section Hematology and Immunology)
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14 pages, 556 KiB  
Article
Pulmonary and Renal Predictors of Mortality in ANCA-Associated Vasculitis: A Regional Experience from Türkiye
by Dilara Bulut Gökten, Sevil Karabağ and Rıdvan Mercan
Biomedicines 2025, 13(6), 1401; https://doi.org/10.3390/biomedicines13061401 - 7 Jun 2025
Viewed by 884
Abstract
Background/Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare autoimmune disease marked by small-vessel inflammation. Pulmonary and renal manifestations are believed to critically influence prognosis, but detailed regional data are lacking. This study aimed to determine the prevalence and prognostic impact of [...] Read more.
Background/Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare autoimmune disease marked by small-vessel inflammation. Pulmonary and renal manifestations are believed to critically influence prognosis, but detailed regional data are lacking. This study aimed to determine the prevalence and prognostic impact of pulmonary and renal involvement in AAV patients in the Thrace region of Türkiye. Methods: A retrospective cohort study was conducted on 78 biopsy-proven AAV patients followed between 2018 and 2025. Demographic, clinical, laboratory, and outcome data were analysed. Logistic regression identified predictors of relapse and mortality. Results: The cohort included 44 granulomatosis with polyangiitis, 30 microscopic polyangiitis, and 4 eosinophilic granulomatosis with polyangiitis patients; 40 were pr3-ANCA positive and 33 MPO-ANCA positive. Pulmonary involvement was observed in 71.8% and renal involvement in 74.4%, and overall mortality was 20.5%. All deaths occurred in patients with pulmonary involvement (28.6% vs. 0%, p = 0.048). Relapse was higher in those with pulmonary (17.9% vs. 4.5%, p = 0.048) and renal (15.5% vs. 5%, p = 0.056) involvement. Multivariate analysis showed that pulmonary involvement (OR 3.82, p = 0.002), renal involvement (OR 4.73, p = 0.013), and rituximab treatment (OR 10.79, p = 0.049) predicted relapse; elevated CRP (OR 1.01, p = 0.003), creatinine (OR 1.42, p = 0.028), hypoalbuminaemia (OR 0.24, p = 0.046), renal (OR 2.86, p = 0.031), and pulmonary (OR 3.21, p = 0.003) involvement predicted mortality. Conclusions: Pulmonary and renal involvement are highly prevalent and represent the strongest predictors of relapse and mortality in AAV patients in this regional cohort. Recognising these risks is essential to guide early interventions and improve patient outcomes. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnostics, and Therapeutics for Rheumatic Diseases)
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27 pages, 2964 KiB  
Article
Approaches for Reducing Expert Burden in Bayesian Network Parameterization
by Bodille P. M. Blomaard, Gabriela F. Nane and Anca M. Hanea
Entropy 2025, 27(6), 579; https://doi.org/10.3390/e27060579 - 29 May 2025
Viewed by 445
Abstract
Bayesian networks (BNs) are popular models that represent complex relationships among variables. In the discrete case, these relationships can be quantified by conditional probability tables (CPTs). CPTs can be derived from data, but if data are not sufficient, experts can be involved to [...] Read more.
Bayesian networks (BNs) are popular models that represent complex relationships among variables. In the discrete case, these relationships can be quantified by conditional probability tables (CPTs). CPTs can be derived from data, but if data are not sufficient, experts can be involved to assess the probabilities in the CPTs through Structured Expert Judgment (SEJ). This is often a burdensome task due to the large number of probabilities that need to be assessed and the structured protocols that need to be followed. To lighten the elicitation burden, several methods have previously been developed to construct CPTs using a limited number of input parameters, such as InterBeta, the Ranked Nodes Method (RNM), and Functional Interpolation. In this study, the burden/accuracy trade-off of InterBeta is researched by applying the method to reconstruct previously elicited CPTs and simulated CPTs, first by comparing these CPTs to ones constructed using RNM and Functional Interpolation. After that, InterBeta extensions are proposed and tested, including an extra mean function (shifted geometric mean), the elicitation of additional middle rows, and the newly proposed extension ExtraBeta. InterBeta with parent weights is found to be the best-performing method, and the ExtraBeta extension is found to be promising and is proposed for further exploration. Full article
(This article belongs to the Section Multidisciplinary Applications)
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25 pages, 10876 KiB  
Article
The Influence of Anti-PAR 1 and Anti-ACE 2 Antibody Levels on the Course of Specific Glomerulonephritis Types
by Maciej Szymczak, Harald Heidecke, Marcelina Żabińska, Łucja Janek, Jakub Wronowicz, Krzysztof Kujawa, Kai Schulze-Forster, Karolina Marek-Bukowiec, Tomasz Gołębiowski and Mirosław Banasik
J. Clin. Med. 2025, 14(9), 3178; https://doi.org/10.3390/jcm14093178 - 4 May 2025
Viewed by 677
Abstract
Background: Anti-PAR 1 (protease-activated receptor 1) and anti-ACE 2 (angiotensin 2-converting enzyme 2) antibodies are a kind of non-HLA (human leukocyte antigens) antibodies postulated to be of significance in autoimmunological diseases and organ transplantation. Methods: We assessed anti-PAR 1 and anti-ACE 2 antibody [...] Read more.
Background: Anti-PAR 1 (protease-activated receptor 1) and anti-ACE 2 (angiotensin 2-converting enzyme 2) antibodies are a kind of non-HLA (human leukocyte antigens) antibodies postulated to be of significance in autoimmunological diseases and organ transplantation. Methods: We assessed anti-PAR 1 and anti-ACE 2 antibody levels in patients with membranous nephropathy n= 18, focal and segmental glomerulosclerosis (FSGS) n = 25, lupus nephritis (LN) n = 17, IgA nephropathy n = 14, mesangial proliferative (non-IgA) glomerulonephritis n = 6, c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis n = 40, p (perinuclear)-ANCA vasculitis n = 16, and compared them with a healthy control group n = 22. Next, we observed the clinical course of the patients (creatinine, total protein, and albumin) up to 2 years and correlated the results with the level of antibodies. Results: The anti-PAR 1 antibody level was lower in membranous nephropathy and FSGS compared to the control group. Anti-PAR 1 antibody levels were higher in secondary compared to primary glomerulonephritis. Both anti-PAR 1 and anti-ACE 2 antibody levels correlated positively (in focal and segmental glomerulosclerosis) or negatively (in lupus nephritis) with total protein and albumin at different time points of observation. Anti-PAR 1 and anti-ACE 2 antibody levels correlated also with creatinine level at one time point of observation in IgA nephropathy. Anti-PAR 1 and anti-ACE 2 antibodies correlated with each other in membranous nephropathy, FSGS, and p- and c-ANCA vasculitis (p < 0.05). Conclusions: The anti-PAR 1 antibody level was lower in membranous nephropathy and focal and segmental glomerulosclerosis compared to the control group. Anti-PAR 1 antibody levels tend to be higher in secondary compared to primary glomerulonephritis. Full article
(This article belongs to the Special Issue Newer Developments in the Field of Glomerular Diseases)
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13 pages, 469 KiB  
Article
Overlap Syndrome of Primary Sjögren Syndrome with Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis Based on the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) Criteria
by Hyun Joon Choi, Jang Woo Ha, Jason Jungsik Song, Yong-Beom Park and Sang-Won Lee
Diagnostics 2025, 15(9), 1099; https://doi.org/10.3390/diagnostics15091099 - 25 Apr 2025
Viewed by 717
Abstract
Background/Objectives: The overlap syndrome of primary Sjögren syndrome (pSS) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (OvSD/pSS/AAV) has been reported in other studies. This study applied the new criteria for AAV proposed by the American College of Rheumatology/European Alliance of Associations for [...] Read more.
Background/Objectives: The overlap syndrome of primary Sjögren syndrome (pSS) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (OvSD/pSS/AAV) has been reported in other studies. This study applied the new criteria for AAV proposed by the American College of Rheumatology/European Alliance of Associations for Rheumatology in 2022 (the ACR/EULAR criteria) to patients with pSS presenting signs and symptoms suggestive of small- and medium-vessel vasculitis. It also investigated the overall frequency of OvSD/pSS/AAV and the major contributing factors to its reclassification. Methods: This study included 116 patients with pSS from March 2005 to December 2020, according to the inclusion criteria, and defined signs and symptoms suggestive of small- or medium-vessel vasculitides as lung parenchymal lesions supporting AAV, peripheral neuropathy, and suspected renal vasculitis. The classification could be made when the total scores for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are ≥5 points and the eosinophilic GPA (EGPA) score is ≥6 points. Results: The median age of the patients was 56.0 years, and 101 patients (87.1%) were women. In total, 95, 12, and 37 patients had lung parenchymal lesions supporting AAV, peripheral neuropathy, and suspected renal vasculitis, respectively. According to the ACR/EULAR criteria for AAV, 35 of 116 (30.2%) patients were reclassified as having OvSD/pSS/AAV. Among these 35 patients, 4 were reclassified as having both OvSD/pSS/MPA and OvSD/pSS/GPA and 1 as having both OvSD/pSS/MPA and OvSD/pSS/EGPA simultaneously. The major contributing factor to the reclassification of OvSD/pSS/AAV was ANCA positivity. Conclusions: The overall frequency of the reclassification of OvSD/pSS/AAV was 30.2% in pSS patients presenting signs and symptoms suggestive of small- and medium-vessel vasculitis. Its likelihood increased according to ANCA positivity. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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17 pages, 4485 KiB  
Article
The Pathogenic Role of Expanded CD8⁺CD28null Angiogenic T Cells in ANCA-Associated Vasculitis
by Haomiao Shen, Jinlin Miao, Haoyang Sun, Kui Zhang, Renli Liu, Zichao Li, Leyang Zhang, Peiyan Zhang, Jiawei Wang, Bei Zhang, Longyu Chen, Zhaohui Zheng and Ping Zhu
Biomedicines 2025, 13(1), 26; https://doi.org/10.3390/biomedicines13010026 - 26 Dec 2024
Viewed by 928
Abstract
Objectives: Angiogenic T cells (Tang) are crucial in promoting angiogenesis, with the loss of CD28 serving as a marker for highly differentiated and senescent T cells. This study aims to investigate the characteristics and potential roles of CD8+CD28null Tang in [...] Read more.
Objectives: Angiogenic T cells (Tang) are crucial in promoting angiogenesis, with the loss of CD28 serving as a marker for highly differentiated and senescent T cells. This study aims to investigate the characteristics and potential roles of CD8+CD28null Tang in patients with ANCA-associated vasculitis (AAV). Methods: A cohort of AAV patients and matched healthy controls (HCs) were analyzed. Flow cytometry was used to assess the profiles of circulating CD8+CD28null Tang. In vitro functional assays were performed to evaluate the pathogenic properties of CD8+CD28null Tang. Results: CD8+CD28null Tang levels were significantly higher in the peripheral blood of AAV patients compared to HCs, and their levels were further increased in AAV patients with MPO⁺, p-ANCA⁺, or interstitial lung disease compared to their respective control groups. Additionally, there was a positive correlation between both the percentage and absolute count of CD8+CD28null Tang and the Birmingham Vasculitis Activity Score (BVAS). In patients with a good treatment response, both the percentage and absolute count of CD8+CD28null Tang were significantly reduced, and this reduction was positively correlated with the decrease in BVAS scores. In vitro studies revealed that CD8+CD28null Tang displayed enhanced chemotactic properties, induced apoptosis in human umbilical vein endothelial cells (HUVECs), and inhibited their proliferation, migration, and tube formation. Conclusions: AAV patients exhibit increased levels of circulating CD8+CD28null Tang, which can be reduced following effective treatment. Furthermore, CD8+CD28null Tang may contribute to the pathogenesis of AAV by promoting apoptosis and inhibiting the proliferation, migration, and tube formation of HUVECs. Full article
(This article belongs to the Section Cell Biology and Pathology)
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19 pages, 5928 KiB  
Article
The Influence of Anti-ETAR and Anti-CXCR3 Antibody Levels on the Course of Specific Glomerulonephritis Types
by Maciej Szymczak, Harald Heidecke, Marcelina Żabińska, Łucja Janek, Jakub Wronowicz, Krzysztof Kujawa, Karolina Bukowiec-Marek, Tomasz Gołębiowski, Karolina Skalec, Kai Schulze-Forster, Andrzej Konieczny and Mirosław Banasik
J. Clin. Med. 2024, 13(24), 7752; https://doi.org/10.3390/jcm13247752 - 19 Dec 2024
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Abstract
Background: Anti-ETAR (endothelin A receptor) antibodies and anti-CXCR3 (C-X-C motif chemokine receptor 3) antibodies are types of non-HLA (human leukocyte antigens) antibodies that could have some influence on the course of glomerulonephritis. The authors aimed to study the influence of these antibodies’ levels [...] Read more.
Background: Anti-ETAR (endothelin A receptor) antibodies and anti-CXCR3 (C-X-C motif chemokine receptor 3) antibodies are types of non-HLA (human leukocyte antigens) antibodies that could have some influence on the course of glomerulonephritis. The authors aimed to study the influence of these antibodies’ levels on the course of specific glomerulonephritis types. Methods: We evaluated the anti-ETAR and anti-CXCR3 antibody levels in the serum of patients with membranous nephropathy (n = 18), focal and segmental glomerulosclerosis (FSGS) (n = 25), systemic lupus erythematosus (n = 17), IgA nephropathy (n = 14), mesangiocapillary glomerulonephritis (n = 6), anti-neutrophil cytoplasmic antibodies (c-ANCA) vasculitis (n = 40), and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16), and we compared their levels with the control group (n = 22). Next, we observed the patients’ clinical parameters (serum creatinine, albumin, total protein) for 2 years and checked the correlation of the clinical course markers with basic receptor antibody level. Results: Our results indicate lower anti-ETAR antibody levels in patients with FSGS and IgA nephropathy compared to the control group. Both types of antibodies correlated with creatinine levels after 2 years of observation in IgA nephropathy. Both types of antibodies seemed to negatively influence the total protein and albumin levels in systemic lupus erythematosus. Conclusions: This prospective observation showed that anti-ETAR and anti-CXCR 3 antibody levels are connected with the course of IgA nephropathy and lupus nephritis. Full article
(This article belongs to the Special Issue Glomerulonephritis: Current Diagnosis, Treatment and Future Options)
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11 pages, 35370 KiB  
Case Report
Rare Clinical Manifestation of Vasculitis
by Oana-Mădălina Manole, Mihai Ștefan Cristian Haba, Iulian-Theodor Matei and Viviana Onofrei
Diagnostics 2024, 14(23), 2623; https://doi.org/10.3390/diagnostics14232623 - 22 Nov 2024
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Abstract
Background: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis usually affects small blood vessels and is characterized by the presence of circulating autoantibodies (c-ANCA or p-ANCA). The risk of cardiovascular events is threefold higher compared to general population, and cardiac manifestations include myocarditis, pericarditis, valvulitis, aortitis, [...] Read more.
Background: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis usually affects small blood vessels and is characterized by the presence of circulating autoantibodies (c-ANCA or p-ANCA). The risk of cardiovascular events is threefold higher compared to general population, and cardiac manifestations include myocarditis, pericarditis, valvulitis, aortitis, or coronary arteritis. Coronary involvement is very rare, but it is a potentially life-threatening manifestation. Methods: We present an atypical cardiac scenario of p-ANCA vasculitis. Results: A 68-year-old woman with known p-ANCA vasculitis and stage 5 chronic kidney disease (CKD) on hemodialysis presented with dizziness accompanied by low blood pressure and chest pain. Electrocardiogram on arrival showed slightly ST-T changes, with negative cardiac biomarkers and no abnormalities in cardiac regional wall motion. Five hours after presentation, the patient repeated chest pain, accompanied by a drop in blood pressure and junctional escape rhythm. The highly sensitive cardiac troponin I (hs-cTnI) was raised at 560 ng/L. Coronary angiography showed coronary arteries without significant stenosis. The provocative test with intracoronary ergonovine demonstrated coronary vasospasm of the anterior descending artery accompanied by chest pain, with resolution after intracoronary nitroglycerin. Under amlodipine, nitrate, acetylsalicylic acid, statin and corticosteroids the patient did not experience the recurrence of angina. Conclusions: This case illustrates coronary involvement, manifested as coronary spasm with favorable outcomes, in systemic vasculitis. The underlying mechanism is immune-mediated inflammation in vascular walls. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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15 pages, 1304 KiB  
Article
Racial Disparities in Inpatient Hospital Outcomes of Primary Sclerosing Cholangitis in United States: Nationwide Analysis
by Ishaan Vohra, Harishankar Gopakumar, Dushyant Singh Dahiya, Michel Kahaleh and Neil Sharma
Diagnostics 2024, 14(22), 2493; https://doi.org/10.3390/diagnostics14222493 - 7 Nov 2024
Viewed by 1514
Abstract
Background: Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic liver disease that may lead to biliary strictures and destruction. It is associated with p-ANCA positivity and inflammatory bowel disease, typically ulcerative colitis. The aim of this study is to investigate the trends of [...] Read more.
Background: Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic liver disease that may lead to biliary strictures and destruction. It is associated with p-ANCA positivity and inflammatory bowel disease, typically ulcerative colitis. The aim of this study is to investigate the trends of inpatient healthcare utilization and mortality from 2008 to 2017 in the United States. Methods: The Nationwide Inpatient Sample (NIS) was examined to identify adult patients diagnosed with PSC between 2008 and 2017. Data on patient demographics, resource utilization, mortality, and PSC-related complications were collected. STATA version 16.0 was employed to perform forward stepwise multivariate regression analysis, generating adjusted odds ratios for both primary and secondary outcomes. Primary outcomes included the inpatient mortality rate and healthcare resource utilization (length of stay, total charges, and trends over the study period). Secondary outcomes focused on trends in associated comorbidities and malignancies in patients with PSC. Results: The average total charge increased by 32.2% ± 2.12 from USD 61,873 ± 2567 in 2008 to USD 91,262 ± 2961 in 2017. Concurrently, the average length of stay declined from 8.07 ± 0.18 days in 2008 to 7.27 ± 0.13 days in 2017. The APR-DRG severity of illness and risk of death significantly increased (major or extreme) during the study period (2008 to 2017), with severity rising from 73.6% to 82.7% (coefficient: 0.21, 95% CI: 0.13–0.28) and risk of death from 45.3% to 60.9% (coefficient: 0.15, 95% CI: 0.08–0.23). The proportion of patients with HCC increased from 1.3% to 7.9% (coefficient: 2.13, 95% CI: 1.9–2.8). Conversely, the percentage of patients with cholangiocarcinoma (CCA) decreased from 5.1% to 2.8% (coefficient: −0.36, 95% CI: −0.25 to −0.46). Conclusions: There was rising mortality and healthcare resource utilization among patients with PSC from the years 2008 to 2017. These trends were paralleled by increasing rates of decompensated cirrhosis, HCC, and liver transplants. However, the incidence of CCA decreased during this time period. African American patients with PSC had worse inpatient mortality outcomes and healthcare utilization as compared to white patients. Further studies are warranted to investigate a possible causal link amongst these trends. Full article
(This article belongs to the Special Issue Gastroenterology and Hepatology: Diagnostics and Management)
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