16,086 results on '"Antibodies, Antinuclear"'
Search Results
2. Pulmonary Hypertension in Patients Attending Sohag University Hospital: A Focus on The Etiology
- Author
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Esraa Abdo Saad, Assistant lecturer of chest diseases and tuberculosis sohag university hospitals
- Published
- 2022
3. Systemic sclerosis in a patient with muscle dystrophy
- Author
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Sara Moutinho-Pereira, Eurico Morais-de-Sá, Helena Greenfield, and P Ricardo Pereira
- Subjects
Male ,Scleroderma, Systemic ,Antibodies, Antinuclear ,Muscles ,Humans ,General Medicine ,Muscular Dystrophies ,Autoimmune Diseases - Abstract
Systemic sclerosis is an autoimmune disease that can result in lung fibrosis, and is strongly associated with the presence of serum anti-topoisomerase-I autoantibodies. A young man with genetic muscular dystrophy caused by titin-cap/telethonin (TCAP) gene mutation, developed a severe restrictive lung disease due to a fibrosing interstitial pneumonia secondary to systemic sclerosis with positive anti-topoisomerase-I antibodies. Using amino acid sequence alignment and protein structure modelling, we found that mutant telethonin exposes an amino acid sequence with significant homology to an immunodominant site of topoisomerase-I. Abnormal telethonin results in a loss of integrity of the sarcomere structure, which might result in rhabdomyolysis and abnormal protein exposure to the immune system. Our preliminary analysis suggests a possible role for mutant sarcomere protein telethonin as an immunogenic target recognised by anti-topoisomerase-I antibodies, which could explain the development of systemic sclerosis in this particular patient.
- Published
- 2024
4. Trauma as a Trigger for Autoimmunity (TATA)
- Published
- 2020
5. Granulocyte colony-stimulating factor as a cause of acute leucocytoclastic vasculitis with anti-Ro and anti-La antibodies
- Author
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Antonio Ji-Xu, Liam Carroll, Thomas Bentley, and Rachael Jarrett
- Subjects
Antibodies, Antinuclear ,Granulocyte Colony-Stimulating Factor ,Humans ,Vasculitis, Leukocytoclastic, Cutaneous ,General Medicine ,Sweet Syndrome ,Skin - Abstract
Granulocyte colony-stimulating factor (G-CSF) administration is associated with a diverse range of cutaneous sequelae. Serious dermatological side effects of G-CSF include the development of Sweet’s syndrome and exacerbations of pre-existing inflammatory disorders such as psoriasis. Here, we describe a report of acute leucocytoclastic vasculitis caused by G-CSF therapy associated with anti-Ro and anti-La antibodies in a patient with multiple myeloma. This case highlights the importance of having a high index of suspicion for acute leucocytoclastic vasculitis in patients with haematological malignancies undergoing G-CSF therapy.
- Published
- 2024
6. Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus.
- Author
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Xu Y, Gao R, Zhang M, Zeng Q, Zhu G, Qiu J, Su W, and Wang R
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- Animals, Mice, Mitochondrial Proteins genetics, Mitochondrial Proteins metabolism, Reactive Oxygen Species metabolism, Antibodies, Antinuclear, Mitochondrial Membranes metabolism, Erythroid Cells metabolism, Erythroid Cells pathology, Disease Models, Animal, Immunoglobulin G metabolism, Mice, Inbred C57BL, Spleen metabolism, Spleen pathology, Membrane Proteins genetics, Membrane Proteins metabolism, Female, Lupus Erythematosus, Systemic genetics, Lupus Erythematosus, Systemic metabolism, Lupus Erythematosus, Systemic pathology, Mice, Knockout
- Abstract
Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout ( Fam210b
-/- ) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b-/- mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.- Published
- 2024
- Full Text
- View/download PDF
7. Cognitive deficits associated with novel intrathecal anti-nuclear antibodies.
- Author
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Maier A, Nickel K, Domschke K, Venhoff N, Tebartz van Elst L, Prüss H, and Endres D
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Cognitive Dysfunction, Antibodies, Antinuclear
- Published
- 2024
- Full Text
- View/download PDF
8. Epidemiological, immunological, and treatment response profile of patients with lupus nephritis in Brazil.
- Author
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Nunes MST, Barbosa Jorge L, Yu L, Woronik V, and Bitencourt Dias C
- Subjects
- Humans, Antibodies, Antinuclear, Biopsy, Brazil epidemiology, Kidney pathology, Retrospective Studies, Lupus Erythematosus, Systemic complications, Lupus Nephritis therapy, Lupus Nephritis drug therapy
- Abstract
Background and Hypothesis: Brazil has the largest number of individuals of African descent outside Africa and a very admixed population. Among cases of lupus nephritis (LN) in the country, there are differences in incidence, and even in severity, depending on the location and characteristics of the population studied. The aim of this study was to describe the clinical and epidemiological characteristics of LN in Brazil, as well as to determine which of those characteristics would be risk factors for a poor renal prognosis., Methods: This was a retrospective, descriptive observational study of patients diagnosed with LN who underwent kidney biopsy between 1999 and 2015 in the Nephrology Department of the Hospital das Clínicas, in São Paulo, Brazil. Data were collected from electronic medical records., Results: We evaluated 398 patients, among who 94.1% and 77.7% tested positive for antinuclear antibodies and anti-DNA antibodies, respectively, whereas 33.7% showed the full-house pattern. The time from LN symptom onset to biopsy was <6 months in 47.5% (early biopsy group) and ≥6 months in 52.5% (late biopsy group). In the early biopsy group, the chronicity index was lower and the activity index was higher. Multivariate analysis showed that a higher chronicity index was the only independent risk factor for progression to requiring kidney replacement therapy., Conclusion: Late biopsy seems to be associated with negative renal outcomes in LN. However, it seems that a higher chronicity index is the main predictor of a poor renal outcome among patients with LN in Brazil., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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9. Clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis.
- Author
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Yang Q, Lai C, Meng C, Chang Q, Wei N, and Wang J
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- Humans, Female, Aged, Aged, 80 and over, Male, Antibodies, Antinuclear, Prognosis, Eye, Aquaporin 4, Retrospective Studies, Neuromyelitis Optica diagnosis, Optic Neuritis diagnosis
- Abstract
Background: Very late-onset neuromyelitis optica spectrum disorder-related optic neuritis is limited to a few case reports., Objective: To investigate the clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis., Methods: This study evaluated 22 patients with first-onset optic neuritis and fulfilled the 2015 diagnosis criteria for neuromyelitis optica spectrum disorders., Results: The mean age at optic neuritis onset was 73.91 ± 4.71 (range: 70-82) years with a female predominance (81.8%; ratio: 4.5:1). Antinuclear antibody seropositivity and seronegativity were identified in 12 (55.5%) and 10 (45.5%) patients, respectively. Severe visual loss persisted in 19 (19/42, 45.3%) eyes at the last follow-up. Although patients with antinuclear antibody seropositivity had a significantly higher frequency of attacks (P = 0.015), but they had a longer median time to reach severe visual loss (37 vs. 26 months; log-rank test, P = 0.023). Multivariate logistic regression analysis revealed antinuclear antibody seropositivity (hazard ratio = 4.849, 95% confidence interval: 1.309-17.965, P = 0.018) as a good predictor of visual acuity improvement., Conclusion: Patients with very late-onset neuromyelitis optica spectrum disorder-related optic neuritis may develop severe optic neuritis, and those with antinuclear antibody seronegativity have a similar clinical presentation but worse outcome than those with seropositivity., (© 2023. Fondazione Società Italiana di Neurologia.)
- Published
- 2024
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10. ANCA in patients with systemic lupus erythematosus. A cross sectional study in Brazilian patients and review of literature.
- Author
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Nisihara R, Vithoft G, Alencar I, Dos Santos TAFG, and Skare TL
- Subjects
- Humans, Male, Antibodies, Antineutrophil Cytoplasmic, Antibodies, Antinuclear, Brazil epidemiology, Cross-Sectional Studies, Myeloblastin, Female, Lupus Erythematosus, Systemic complications, Vasculitis complications
- Abstract
Background: Antineutrophil cytoplasmatic antibodies (ANCA) have been detected in patients with systemic lupus erythematosus (SLE). In this study, we investigated the presence of ANCA in a sample of Brazilian SLE patients and its possible associations with clinical and serological outcomes. Additionally, we reviewed the literature of on ANCA in SLE., Results: The presence of ANCA was detected in 130 patients using indirect immunofluorescence (IIF). The test was positive in 29.9% of the cases (17.6% pANCA and 11.5% cANCA). Male sex and peripheral vasculitis were more prevalent in the ANCA-positive sample. cANCA was associated with lupus anticoagulant and pANCA had a positive association with peripheral vasculitis and a negative association with anti- SSB/La antibodies. In the 22 studies included in the literature review, a wide range of ANCA positivity was found (13% to 81.1% by IIF and 0 to 22.2% by ELISA). ANCA was associated with renal damage in the Asian population. Although other associations have been found in isolated studies, they were not consistently reported., Conclusions: The ANCA prevalence found in this Brazilian sample was within the range reported in the literature and these autoantibodies were more frequent in males and in patients with vasculitis. The literature showed controversial results on the association between ANCA and SLE disease activity or clinical characteristics., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
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11. Antinuclear antibody-associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosus.
- Author
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Granel J, Fernandes H, Bader-Meunier B, Guth A, Richer O, Pillet P, Leverger G, Ducassou S, Fahd M, Pasquet M, Garnier N, Barlogis V, Guitton C, Jeziorski E, Thomas C, Bayart S, Cheikh N, Paillard C, Abou Chahla W, Chastagner P, Neven B, Millot F, Lejeune J, Li-Thiao Te V, Armari-Alla C, Briandet C, Carausu L, Deparis M, Piguet C, Benadiba J, Marie-Cardine A, Stephan JL, Pellier I, Pluchart C, Doré E, Michaux K, Héritier S, Leblanc T, and Aladjidi N
- Subjects
- Adolescent, Adult, Child, Humans, Young Adult, Antibodies, Antinuclear, Prospective Studies, Risk Factors, Cytopenia, Lupus Erythematosus, Systemic diagnosis
- Abstract
Abstract: Autoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE of childhood-onset ANA-associated AIC. In the French national prospective OBS'CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer ≥1/160) and a subgroup of children who developed SLE were described. ANA were positive in 355 of 1803 (20%) children with AIC. With a median follow-up of 5.8 (range, 0.1-29.6) years, 79 of 355 (22%) patients developed SLE at a median age of 14.5 (1.1-21.4) years; 20% of chronic immune thrombocytopenic purpura, 19% of autoimmune hemolytic anemia, and 45% of Evans syndrome. None of the patients with ANA-negative test developed SLE. Severe manifestations of SLE were observed in 21 patients, and 2 patients died. In multivariate analysis including patients with positive ANA within the first 3 months after AIC diagnosis, age >10 years at AIC diagnosis (relative risk [RR], 3.67; 95% confidence interval [CI], 1.18-11.4; P = .024) and ANA titer >1/160 (RR, 5.28; 95% CI, 1.20-23.17; P = .027) were associated with the occurrence of SLE after AIC diagnosis. ANA-associated AIC is a risk factor for progression to SLE, especially in children with an initial ANA titer >1/160 and an age >10 years at AIC diagnosis. ANA screening should be recommended in children with AIC, and patients with ANA should be monitored long-term for SLE, with special attention to the transition period. This trial was registered at www.ClinicalTrials.gov as #NCT05937828., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
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12. Antinuclear antibodies may predict the development of immune-related adverse events in asymptomatic patients treated with immune checkpoint inhibitors: results from a single-center cohort.
- Author
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Ceccarelli F, Natalucci F, Picciariello L, Cirillo A, Olivieri G, Veroli M, Pisegna S, Ciancarella C, Gelibter A, Picone V, Santini D, Botticelli A, and Conti F
- Subjects
- Humans, Aged, Immune Checkpoint Inhibitors adverse effects, Autoantibodies, Autoimmunity, Antibodies, Antinuclear, Arthritis
- Abstract
We aim at investigating the association between subclinical autoimmunity and immune-related adverse events (irAEs) in a cohort of patients treated by immune checkpoint inhibitors for solid metastatic cancer. In the context of an oncology/rheumatology outpatient clinic, we evaluated patients treated with anti-PD-1 or anti-PD-L1. Before treatment, each patient underwent a physical evaluation and a blood sample to identify the presence of a set of autoantibodies. Indeed, all the patients were followed during treatment to identify irAEs and to assess the association with autoantibodies. Fifty-one patients (M/F 16/35; median age 70 years, IQR 16.5) were evaluated; 34.8% of patients showed ANA positivity, 6.5% ENA positivity (anti-SSA), 4.3% Ratest positivity, and 2.1% (one patient) ACPA positivity. During a median period of 21 months (IQR 38.75), 39.2% of patients developed irAEs. Musculo-skeletal manifestations, in particular arthritis, were the most frequent. We found a significant association between the positivity for ANA and the development of irAES (p = 0.03, RR 2.01, 95% CI 1.03-3.92). Furthermore, the progression-free survival was significantly longer in patients developing irAEs compared to those who are not experiencing these events (p = 0.007). This study underlines the potential role of ANA positivity as a predictive biomarker for the development of irAEs., (© 2024. The Author(s).)
- Published
- 2024
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13. Development of a nomogram for membranous nephropathy prediction in patients with primary Sjögren's syndrome: a 6-year retrospective study.
- Author
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Guo L, Zhao S, and Liu X
- Subjects
- Humans, Retrospective Studies, Nomograms, Antibodies, Antinuclear, Sjogren's Syndrome, Glomerulonephritis, Membranous complications
- Abstract
Objectives: Nephritis is a life-threatening complication of primary Sjögren's syndrome (pSS), with membranous nephropathy (MN) being prevalent. Renal biopsy is the gold standard for MN diagnosis, but it is invasive and cannot be repeatedly performed. This study aimed to develop a nomogram for the prediction of MN in patients with pSS., Methods: This retrospective study included patients with pSS admitted to the Rheumatology and Immunology Department of the First Affiliated Hospital of China Medical University between January 2015 and January 2021. A nomogram was developed using multivariable logistic regression analysis and evaluated using receiver operating characteristic (ROC) curve analysis. Bootstrap resampling analysis (1,000 times) was performed to evaluate the nomogram for discrimination and the calibration curve for consistency., Results: A total of 237 patients with pSS [aged 53.00 (44.00, 61.00) years] were included, with 35 pSS-MN patients. Based on clinical practice and multivariable logistic regression analysis, seven variables associated with pSS-MN were selected, including white blood cells, creatine, complement 3, rheumatoid factor, antinuclear antibodies, anti-SSA antibody, and interstitial lung disease. The area under the ROC curve was 0.860 (95% confidence interval: 0.796-0.919), indicating good predictive power. In addition, the nomogram exhibited excellent performance, as demonstrated by the calibration curve and decision curve analysis., Conclusion: This study developed a risk prediction nomogram for MN in patients with pSS, with high predictive power. It may be used to improve the management of patients with pSS., Competing Interests: The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Zhao and Liu.)
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- 2024
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14. Anti-survival motor neuron complex antibodies as a novel biomarker for pulmonary arterial hypertension and interstitial lung disease in mixed connective tissue disease.
- Author
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Todoroki Y, Satoh M, Kubo S, Kosaka S, Fukuyo S, Nakatsuka K, Saito K, Tanaka S, Nakayamada S, and Tanaka Y
- Subjects
- Humans, Antibodies, Antinuclear, Biomarkers, Familial Primary Pulmonary Hypertension complications, Motor Neurons, Mixed Connective Tissue Disease complications, Pulmonary Arterial Hypertension complications, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial complications, Lupus Erythematosus, Systemic complications
- Abstract
Objective: The presence of anti-U1 RNP antibodies (Abs) is critical for diagnosing MCTD. The aim of this study is to evaluate the clinical relevance of anti-survival motor neuron (SMN) complex Abs, which often coexist with anti-U1 RNP Abs., Methods: A total of 158 newly diagnosed consecutive cases of SLE, SSc or MCTD with anti-U1 RNP Abs were enrolled in this multicentre observational study between April 2014 and August 2022. Serum anti-SMN complex Abs were screened by immunoprecipitation of 35S-methionine-labelled cell extracts, and associations between anti-SMN complex Abs positivity and clinical characteristics were analysed., Results: Anti-SMN complex Abs were detected in 36% of MCTD patients, which was significantly higher than that in SLE (8%) or SSc (12%). Among MCTD patients classified based on the combination of the clinical features of SLE, SSc and idiopathic inflammatory myopathies, anti-SMN complex Abs showed the highest prevalence in a subset with clinical features of all three components. Anti-SMN complex Abs-positive MCTD had a higher prevalence of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), which are related to poor prognosis, than negative patients. Moreover, all three cases of death within 1 year of the treatment were positive for anti-SMN complex Abs., Conclusions: Anti-SMN complex Abs is the first biomarker of a typical subset of MCTD which bears organ damages such as PAH and ILD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
- Full Text
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15. Comparison of the SLE Risk Probability Index (SLERPI) scale against the European League Against Rheumatism/American College of Rheumatology (ACR/EULAR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria.
- Author
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Castañeda-González JP, Mogollón Hurtado SA, Rojas-Villarraga A, Guavita-Navarro D, Gallego-Cardona L, Arredondo AM, Cubides H, Ibáñez C, Escobar A, and Cajamarca-Barón J
- Subjects
- Humans, Female, United States, Adult, Male, Antibodies, Antinuclear, Adrenal Cortex Hormones, Rheumatology, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic epidemiology, Rheumatic Diseases
- Abstract
Introduction: Timely diagnosis and proper recognition of Systemic Lupus Erythematosus (SLE) is essential to establish early management in inpatients and outpatients. There are different classification scales to identify SLE, which include various clinical and serological aspects. In 2021, the SLE Risk Probability Index (SLERPI) was published, which focuses predominantly on the clinical characteristics of patients with suspected SLE and uses a simple algorithm for early recognition of the disease. The aim of this study is to compare the European League Against Rheumatism/American College of Rheumatology (ACR/EULAR) classification criteria, the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and the SLERPI criteria in a cohort of Colombian patients with SLE and to analyze the correlations observed between their absolute scores., Methods: A registry of SLE patients from two referral hospitals in Bogotá, Colombia, was used. 2021 SLERPI, 2019 ACR/EULAR, and 2012 SLICC scores were calculated for each patient and the correlations found between the scales were analyzed. The sensitivities of each were compared, and frequency analyses were conducted among different clinical and laboratory variables., Results: Between 2016 and 2019, 146 patients diagnosed with SLE were registered, including inpatients and outpatients. The median age was 36 years (interquartile range 26-51), and 82.2% were women. According to the SLERPI criteria, a high prevalence of antinuclear antibodies (92%), immunological disorders (71%), and arthritis (64%) were observed. The most used treatments were corticosteroids (87.6%) and chloroquine (67.8%). A Spearman evaluation analysis was performed, with a moderately strong correlation of 0.76 ( p = .000) between the SLERPI and ACR/EULAR scales and very strong correlation of 0.80 ( p = .000) between the SLERPI and SLICC. Patients classified with SLE according to the SLERPI scale exhibited a higher incidence of hematological compromise, along with elevated levels of serological markers such as anti-DNA antibodies. Additionally, this group more commonly received treatments involving corticosteroids and azathioprine, and displayed a higher prevalence of hypertension., Conclusion: The SLERPI scale could be useful in the diagnosis of SLE, especially in early stages, given its good correlation with other classification scales and its good sensitivity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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16. Rowell's syndrome with Condyloma acuminatum: A case report.
- Author
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Li M, Huang R, Wu W, Lu Y, Liu Q, and Li W
- Subjects
- Female, Humans, Syndrome, Antibodies, Antinuclear, Lupus Erythematosus, Systemic, Erythema Multiforme diagnosis, Erythema Multiforme pathology
- Abstract
Rowell's syndrome is an autoimmune disease characterized by lupus erythematosus, erythema multiforme skin lesions, and speckled antinuclear antibody. We report the case of a woman who presented with erythema multiforme with target-type skin lesions and vulvar vegetation who fulfilled the criteria for Rowell's syndrome and condyloma acuminatum. The simultaneous occurrence of both conditions has rarely been reported in the literature., Competing Interests: Declaration of competing interest The authors confirm that they have obtained all necessary patient consent forms. Within these documents, the patients have willingly provided their consent for the publication of their images and other clinical information in the journal. The patients understand that their names and initials will be kept confidential, with every effort made to protect their identity; however, absolute anonymity cannot be guaranteed., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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17. Prevalence and sociodemographic correlates of antinuclear antibody testing by indirect immunofluorescence or solid-phase assays in a Spanish population: the Camargo Cohort.
- Author
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Irure-Ventura J, Martínez-Revuelta D, López-Hoyos M, Martín-Millán M, Nan D, Pariente E, Pardo-Lledías J, Comins-Boo A, Olmos JM, Martínez-Taboada VM, and Hernández JL
- Subjects
- Female, Humans, Fluorescent Antibody Technique, Indirect methods, Prevalence, Autoantibodies, Immunoassay methods, Antibodies, Antinuclear, Autoimmune Diseases diagnosis, Autoimmune Diseases epidemiology
- Abstract
Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs., (© 2023. The Author(s).)
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- 2024
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18. Obsessive-Compulsive Disorder With Inflammatory Cerebrospinal Fluid Changes and Intrathecal Antinuclear Antibody Staining
- Author
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Dominique Endres, Miriam A. Schiele, Björn C. Frye, Andrea Schlump, Bernd Feige, Kathrin Nickel, Benjamin Berger, Marco Reisert, Horst Urbach, Katharina Domschke, Nils Venhoff, Harald Prüss, and Ludger Tebartz van Elst
- Subjects
Obsessive-Compulsive Disorder ,Antibodies, Antinuclear ,Humans ,ddc:610 ,Biological Psychiatry - Published
- 2023
19. Neonatal lupus: a clinical challenge
- Author
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Sofia Fraga, Margarida Pinto, Sandra Sousa, and Filipa Costa Cascais
- Subjects
medicine.medical_specialty ,Autoimmunity ,Clinical manifestation ,medicine.disease_cause ,Internal medicine ,Neonatal lupus ,medicine ,Lupus Erythematosus, Cutaneous ,Humans ,Lupus Erythematosus, Systemic ,Family history ,biology ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Transplacental ,Infant ,General Medicine ,Dermatology ,Rheumatology ,Antibodies, Antinuclear ,Skin biopsy ,biology.protein ,Female ,Antibody ,business - Abstract
Neonatal lupus is an uncommon entity. The main manifestations are cutaneous and cardiac. It is caused by transplacental passage of maternal antibodies (anti-Ro/SSA or anti-La/SSB), and the diagnosis is made by its detection in the mother or child. The authors present a case of a 4-month-old female infant, with a cutaneous eruption since she was 2 months old. She had no relevant personal or family history. Analytically she had an increase in liver enzymes. The histological aspect of the skin biopsy led to an autoimmunity study on the mother and infant, both of which had positive anti-Ro/SSA antibodies, confirming the diagnosis of neonatal lupus. Cardiological study was normal. The skin lesions resolved during the first year of life. Skin lesions are the most frequent non-cardiac clinical manifestation of neonatal lupus, and they are self-limited. When there is no family history, nor cardiac involvement, the diagnosis can be challenging.
- Published
- 2023
20. The evaluation of cellular immune function in elderly patients with systemic lupus erythematosus
- Author
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Kun Men, Yu Chen, Jingwei Zhang, and Dianjun Wei
- Subjects
antibodies, antinuclear ,extractable nuclear antibody ,lupus erythematosus, systemic ,cd4+ t-cells ,cd8+ t-cells ,Medicine - Abstract
Background/Aims To evaluate cellular immune function in systemic lupus erythematosus (SLE) patients over 60 years old, the association between antinuclear antibody (ANA) titers and the ratio of CD4+ /CD8+ was analyzed in this study. The distribution of ANAs and extractable nuclear antibodies (ENAs) in a healthy elderly population was also investigated. Methods Serum ANA titers were assayed by indirect immunofluorescence (IIF) and the CD4+ /CD8+ T-cell ratio was determined by flow cytometry in 76 SLE patients and 30 healthy control individuals. IIF of cytoplasm and nuclear and nucleolar staining were performed on samples taken from 286 healthy elderly individuals. ENA levels were determined using a strip enzyme immunoassay among patients that tested positive for ANAs. Results ANA titers were negative in the 30 control individuals, but were positive in the 76 SLE patients. Based on ANA titers, the SLE patients were stratified to low (≤ 1:320), medium (1:640 to 1:1,280), and high (≥ 1:2,560) titer groups. The average CD4+ /CD8+ ratio of the SLE group was significantly lower than that of the control group. Among the 286 healthy elderly volunteers, 59 (20.63%) tested positive for ANAs. A homogeneous pattern was present in 47.46% of those 59 patients and a granule pattern in the karyoplasm was present in 33.90%. Furthermore, of the 59 patients, ENAs immunoassay was positive in 18 (30.51%); Sjogren syndrome-related antigen A (SSA)/52 kd and Sjogren syndrome antigen B (SSB)/La were the two major antibodies. Conclusions The significantly lower CD4+ /CD8+ ratio among SLE patients over 60 years old is associated with deregulated immune responses and the development of SLE. A low ANA titer (1:160) is common in healthy elders, emphasizing the importance of considering age when determining if the evaluation of ANA titers is to be included in autoimmune disease diagnosis.
- Published
- 2019
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21. Identifying antinuclear antibody positive individuals at risk for developing systemic autoimmune disease: development and validation of a real-time risk model.
- Author
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Barnado A, Moore RP, Domenico HJ, Green S, Camai A, Suh A, Han B, Walker K, Anderson A, Caruth L, Katta A, McCoy AB, and Byrne DW
- Subjects
- Female, Humans, Antibodies, Antinuclear, Autoantibodies, Electronic Health Records, Male, Autoimmune Diseases diagnosis, Rheumatology
- Abstract
Objective: Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas for clinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. We developed and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals., Methods: Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori , we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples., Results: We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set., Conclusion: We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Barnado, Moore, Domenico, Green, Camai, Suh, Han, Walker, Anderson, Caruth, Katta, McCoy and Byrne.)
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- 2024
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22. Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.
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Liphaus BL, Silva SC, Palmeira P, Silva CA, Goldenstein-Schainberg C, and Carneiro-Sampaio M
- Subjects
- Humans, Antibodies, Antinuclear, Apoptosis, bcl-2-Associated X Protein, Caspase 3, Killer Cells, Natural, Receptors, Tumor Necrosis Factor, Type I, Dermatomyositis complications, Lupus Erythematosus, Systemic, Lupus Nephritis
- Abstract
Background: Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement., Methods: Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels., Results: Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls., Conclusion: This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liphaus, Silva, Palmeira, Silva, Goldenstein-Schainberg and Carneiro-Sampaio.)
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- 2024
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23. Coronary Ectasia and Antinuclear Antibodies: Another Clue to the Role of Immunology in Vascular Disease.
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Lozano I, Suárez A, and Rodriguez-Carrio J
- Subjects
- Humans, Antibodies, Antinuclear, Dilatation, Pathologic, Coronary Angiography, Coronary Artery Disease, Vascular Diseases
- Abstract
Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.
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- 2024
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24. Low CD4 + T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy.
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Torell A, Stockfelt M, Blennow K, Zetterberg H, Akhter T, Leonard D, Rönnblom L, Pihl S, Saleh M, Sjöwall C, Strevens H, Jönsen A, Bengtsson AA, Trysberg E, Majczuk Sennström M, Zickert A, Svenungsson E, Gunnarsson I, Bylund J, Jacobsson B, Rudin A, and Lundell AC
- Subjects
- Female, Humans, Pregnancy, Antibodies, Antinuclear, Autoantibodies, DNA, Interferon-alpha, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic pathology, Lymphopenia, T-Lymphocytopenia, Idiopathic CD4-Positive etiology, T-Lymphocytopenia, Idiopathic CD4-Positive immunology
- Abstract
Background: Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy., Methods: Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4 + and CD8 + T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren's syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and β
2 glycoprotein I [β2 GPI]) was assessed with multiplexed bead assay. IFNα protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records., Results: Women with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4 + T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4 + T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4 + T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4 + T cell count was unrelated to treatment., Conclusion: Lymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways., (© 2024. The Author(s).)- Published
- 2024
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25. Clinical and serological characteristics of anti-Ro/SS-A and anti-La/SS-B negative primary Sjögren's syndrome: a comparative study.
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Bodakçi E
- Subjects
- Male, Humans, Female, Adult, Middle Aged, Retrospective Studies, Rheumatoid Factor, Antibodies, Antinuclear, Autoantibodies, Sjogren's Syndrome diagnosis, Arthritis
- Abstract
Objective: This study aimed to describe the clinical spectrum of primary Sjögren's syndrome (pSS) patients with anti-Ro/SS-A and anti-La/SS-B negativity., Patients and Methods: From a single-center study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, those with triple seronegativity anti-Ro/SS-A (anti-Sjögren's-syndrome-related antigen A autoantibody), anti-La/SS-B (anti-Sjögren's-syndrome-related antigen B autoantibody), rheumatoid factor (RF) (-) and antinuclear antibody (ANA)(+)] or [anti-Ro/SS-A(-), anti-La/ SS-B(-), RF(+) and ANA(-)] and quad¬ruple seronegativity [anti-Ro/SS-A(-), anti-La/SS-B(-), RF(-) and ANA(-)] were identified retrospectively. Clinical, serological, and laboratory features were compared. A comparison between triple and quadruple seronegative pSS patients was also performed., Results: We included 184 patients (168 women, 16 men) with a mean age at diagnosis of 50.1±13.1 years. The most common subjective presenting features at the time of the diagnosis were dry mouth (94.5%) and dry eye (91.3 %). ANA positivity was 57.0%, and RF positivity was 30.4%. Salivary gland enlargement, arthritis, Raynaud's phenomenon, vasculitis, interstitial lung disease (ILD), neurological involvement, primary biliary cholangitis (PBC), lymphopenia, and thrombocytopenia were observed in ANA+ and RF+ patients but not in seronegative patients (p<0.0001). Arthritis was observed most frequently in RF-positive patients and secondly in ANA-positive patients, whereas arthritis was not observed in seronegative patients (p<0.0001). Autoimmune thyroiditis was present in 65 patients (35.0%), 84.6% of these patients were ANA positive while 12.3% were ANA negative (p=0.0014), RF positivity was 30.7% while RF negativity was 6.15% (p=0.001), 23.0% were both ANA and RF positive while 12.3% were seronegative (p<0.002). Cryoglobulinemia, renal disease, and lymphoma were not observed in any of the patients., Conclusions: We confirm the strong influence of immunological markers on the phenotype of primary SS at diagnosis.
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- 2024
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26. SLE criteria are by necessity still based on clinical (and immunological) criteria items.
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Aringer M and Mosca M
- Subjects
- Humans, Autoantibodies, Antibodies, Antinuclear, Lupus Erythematosus, Systemic diagnosis, Rheumatology, Rheumatic Diseases
- Abstract
Introduction: The 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) rely on clinical and routine immunological items. The criteria have anti-nuclear antibodies (ANA) as an obligatory entry criterion; items are weighted and ordered in domains. While demonstrating good sensitivity and specificity, the lack of a more molecular approach to some came as a disappointment., Areas Covered: Based on a non-systematic literature search, this review covers items investigated in the EULAR/ACR classification criteria project, but not included in the set of criteria. It demonstrates data on the importance of the criteria and analyses implications of multiomics studies started around the same time as the criteria project. We also discuss data on the type-I interferon signature and on other cytokines, as well as on complement proteins and their split products. The final part deals with the variability in disease and the apparently random pattern of autoantibodies and organ manifestations in individual patients., Expert Opinion: We believe that the EULAR/ACR criteria are a relevant step toward the right direction. A more uniform molecular approach will not be feasible as long as the molecular mechanisms underlying the tendency toward producing multiple autoantibodies are not better understood.
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- 2024
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27. Immunosuppressive Treatment for an anti-U 1 Ribonucleoprotein Antibody-positive Patient with Pulmonary Arterial Hypertension.
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Matsumoto K, Miyawaki Y, Katsuyama T, Nakadoi T, Shidahara K, Hirose K, Nawachi S, Asano Y, Katayama Y, Katsuyama E, Takano-Narazaki M, Matsumoto Y, Mori A, Akagi S, Sada KE, and Wada J
- Subjects
- Female, Humans, Adult, Immunosuppressive Agents therapeutic use, Antibodies, Antinuclear, Adrenal Cortex Hormones, Ribonucleoproteins, Pulmonary Arterial Hypertension drug therapy
- Abstract
A 34-year-old woman with pulmonary arterial hypertension (PAH) was admitted to the hospital. She had been diagnosed with PAH three years earlier and treated with triple vasodilator therapy. She was positive for anti-U
1 ribonucleoprotein antibodies but did not show any other symptoms associated with autoimmune diseases. Corticosteroid and cyclophosphamide therapy was administered, suspecting the involvement of immunological pathophysiology. After 3 weeks, the mean pulmonary artery pressure decreased from 50 to 38 mmHg without any change in the vasodilators. Immunosuppressive therapy was effective in this patient with PAH with an anti-U1 ribonucleoprotein-antibody-positive response and might be an option for patients with these specific features.- Published
- 2024
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28. Expert Perspective on a Clinical Challenge: Lupus and Pregnancy.
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Tarter L and Bermas BL
- Subjects
- Pregnancy, Humans, Infant, Newborn, Female, Pregnancy Outcome, Antibodies, Antinuclear, Pre-Eclampsia, Pregnancy Complications, Premature Birth, Lupus Erythematosus, Systemic
- Abstract
Systemic lupus erythematosus (SLE), a multiorgan systemic inflammatory disorder, predominantly affects women during their reproductive years. In this review, we summarize the state of knowledge about preconception planning and management of SLE during pregnancy. Achieving remission or low disease activity for several months on medications compatible with pregnancy prior to conception is essential to decreasing the risk of disease flare and improving pregnancy outcomes, including pre-eclampsia, preterm birth, and intrauterine growth restriction. With close management and well-controlled disease before and during pregnancy, <10% of patients flare. All patients with SLE should remain on hydroxychloroquine unless contraindicated. Expectant mothers with a history of antiphospholipid syndrome should be treated with anticoagulant therapy during pregnancy. Women with anti-Ro/SSA or anti-La/SSB antibodies require additional monitoring because their offspring are at increased risk for congenital heart block. Patients with SLE should be offered low-dose aspirin starting at the end of the first trimester to reduce the risk of pre-eclampsia. Flares of SLE during pregnancy require escalation of therapy. The immunosuppressives azathioprine, tacrolimus, and cyclosporine are compatible with pregnancy, and biologic agents can also be considered. Glucocorticoid use in pregnancy should be limited to the lowest effective dose. Mycophenolate mofetil/mycophenolic acid, methotrexate, leflunomide, and cyclophosphamide are known to be teratogenic and are contraindicated in pregnancy. Distinguishing a flare of lupus nephritis during pregnancy from pre-eclampsia can be particularly challenging. Overall, outcomes in pregnancy for women with lupus are improving, but gaps in knowledge about optimal management strategies persist., (© 2023 American College of Rheumatology.)
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- 2024
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29. Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies.
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Buyon JP, Masson M, Izmirly CG, Phoon C, Acherman R, Sinkovskaya E, Abuhamad A, Makhoul M, Satou G, Hogan W, Pinto N, Moon-Grady A, Howley L, Donofrio M, Krishnan A, Ahmadzia H, Levasseur S, Paul E, Owens S, Cumbermack K, Matta J, Joffe G, Lindblade C, Haxel C, Kohari K, Copel J, Strainic J, Doan T, Bermudez-Wagner K, Holloman C, Sheth SS, Killen S, Tacy T, Kaplinski M, Hornberger L, Carlucci PM, Izmirly P, Fraser N, Clancy RM, and Cuneo BF
- Subjects
- Child, Pregnancy, Humans, Female, Autoantibodies, Prospective Studies, Antibodies, Antinuclear, Echocardiography methods, Atrioventricular Block diagnosis, Atrioventricular Block epidemiology, Pregnancy Complications
- Abstract
Objective: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB)., Methods: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB., Results: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal., Conclusion: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms., (© 2023 American College of Rheumatology.)
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- 2024
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30. A Case of Persistent Lung Masses After Treatment of Hodgkin Lymphoma.
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Sinha T, Fu J, Bains A, and Gangemi A
- Subjects
- Female, Humans, Middle Aged, Autoantibodies, Antibodies, Antinuclear, Sjogren's Syndrome diagnosis, Hodgkin Disease diagnosis, Hodgkin Disease therapy, Scleritis
- Abstract
Case Presentation: The patient is a 49-year-old woman who had never used tobacco with a history of relapsing polychondritis and episcleritis. She sought treatment at our clinic for evaluation of multiple lung masses. She originally received a diagnosis by chest radiography performed to rule out sarcoidosis as the cause of episcleritis showing an abnormal findings. She had no contributory surgical, family, or social history. The autoimmune markers were notable for positive rheumatoid factor (153 IU/mL) and elevated erythrocyte sedimentation rate (97 mm/h) and C-reactive protein (65.5 mg/L). Pertinent studies with negative results included antineutrophilic cytoplasmic antibody, antinuclear antibody, cyclic citrullinated peptide antibody, Sjogren syndrome-related antigen A, and Sjogren syndrome-related antigen B tests., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
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- 2024
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31. Ruxolitinib for Refractory PL-12 Antisynthetase Syndrome-Associated Angioedema-Like Panniculitis With Clonal T-Cell Receptor Gene Rearrangement.
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Sengupta S, Law B, Sennett R, Jedrych JJ, Albayda J, and Kang JK
- Subjects
- Humans, Antibodies, Antinuclear, Genes, T-Cell Receptor, Autoantibodies, Myositis diagnosis, Myositis drug therapy, Panniculitis diagnosis, Panniculitis drug therapy, Nitriles, Pyrazoles, Pyrimidines
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- 2024
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32. TLR7 activation of age-associated B cells mediates disease in a mouse model of primary Sjögren's disease.
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Punnanitinont A, Kasperek EM, Zhu C, Yu G, Miecznikowski JC, and Kramer JM
- Subjects
- Humans, Mice, Female, Animals, Autoantibodies, Toll-Like Receptor 7 metabolism, Cytokines metabolism, Disease Models, Animal, Antibodies, Antinuclear, Sjogren's Syndrome
- Abstract
Primary Sjögren's disease (pSD) (also referred to as Sjögren's syndrome) is an autoimmune disease that primarily occurs in women. In addition to exocrine gland dysfunction, pSD patients exhibit B cell hyperactivity. B cell-intrinsic TLR7 activation is integral to the pathogenesis of systemic lupus erythematosus, a disease that shares similarities with pSD. The role of TLR7-mediated B cell activation in pSD, however, remains poorly understood. We hypothesized that age-associated B cells (ABCs) were expanded in pSD and that TLR7-stimulated ABCs exhibited pathogenic features characteristic of disease. Our data revealed that ABC expansion and TLR7 expression were enhanced in a pSD mouse model in a Myd88-dependent manner. Splenocytes from pSD mice showed enhanced sensitivity to TLR7 agonism as compared with those derived from control animals. Sort-purified marginal zone B cells and ABCs from pSD mice showed enhanced inflammatory cytokine secretion and were enriched for antinuclear autoantibodies following TLR7 agonism. Finally, IgG from pSD patient sera showed elevated antinuclear autoantibodies, many of which were secreted preferentially by TLR7-stimulated murine marginal zone B cells and ABCs. These data indicate that pSD B cells are hyperresponsive to TLR7 agonism and that TLR7-activated B cells contribute to pSD through cytokine and autoantibody production. Thus, therapeutics that target TLR7 signaling cascades in B cells may have utility in pSD patients., Competing Interests: Conflict of interest statement. None of the authors have any conflicts of interest related to this work., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)
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- 2024
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33. The Binding Properties of Antibodies to Z-DNA in the Sera of Normal Healthy Subjects.
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Pisetsky DS, Gedye MJ, David LA, and Spencer DM
- Subjects
- Animals, Humans, Healthy Volunteers, Antibodies, Antinuclear, Immunoglobulin G, Immunoglobulin A, DNA, Z-Form
- Abstract
Antibodies to DNA are a diverse set of antibodies that bind sites on DNA, a polymeric macromolecule that displays various conformations. In a previous study, we showed that sera of normal healthy subjects (NHS) contain IgG antibodies to Z-DNA, a left-handed helix with a zig-zig backbone. Recent studies have demonstrated the presence of Z-DNA in bacterial biofilms, suggesting a source of this conformation to induce responses. To characterize further antibodies to Z-DNA, we used an ELISA assay with brominated poly(dGdC) as a source of Z-DNA and determined the isotype of these antibodies and their binding properties. Results of these studies indicate that NHS sera contain IgM and IgA as well as IgG anti-Z-DNA antibodies. As shown by the effects of ionic strength in association and dissociation assays, the anti-Z-DNA antibodies bind primarily by electrostatic interactions; this type of binding differs from that of induced anti-Z-DNA antibodies from immunized animals which bind by non-ionic interactions. Furthermore, urea caused dissociation of NHS anti-Z-DNA at molar concentrations much lower than those for the induced antibodies. These studies also showed IgA anti-Z-DNA antibodies in fecal water. Together, these studies demonstrate that antibodies to Z-DNA occur commonly in normal immunity and may arise as a response to Z-DNA of bacterial origin.
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- 2024
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34. Four clinical and biological phenotypes in antiphospholipid syndrome: a cluster analysis of 174 patients with antinuclear antibody tests.
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Ottavi M, Toulon P, Casolla B, and Martis N
- Subjects
- Male, Middle Aged, Humans, Female, Antibodies, Antinuclear, Cluster Analysis, Phenotype, Recurrence, Antiphospholipid Syndrome diagnosis, Venous Thromboembolism, Autoimmune Diseases
- Abstract
Introduction: Antiphospholipid syndrome (APS) is an autoimmune thrombotic disease with various systemic presentations. This study aimed to identify homogeneous groups of patients based on a non-supervised hierarchical cluster analysis and assess the rate of relapse associated with antinuclear antibodies (ANA)., Methods: This retrospective observational study enrolled patients, over a 90-month period, who had APS as defined by the 2006 Sydney classification criteria, and for whom ANA workup was performed. Agglomerative unsupervised hierarchical clustering was conducted to classify patients into subgroups using 24 variables reflecting a range of clinical and biological baseline features associated with APS., Results: Hundred and seventy-four patients were included and were categorized into four phenotypes. Cluster 1 (n=73) associated mostly middle-aged men with risk factors for cardiovascular disease. Obstetrical APS with low-risk thrombosis made up cluster 2 (n=25). Patients with venous thromboembolism (VTE), microvascular findings and double/triple positive APL antibodies (50%) were represented in cluster 3 (n=33). Whereas cluster 4 (n=43) characterized a predominantly female subpopulation with positive ANA and systemic lupus (n=23) that exhibited a high thrombotic risk and more frequent relapses (n=38) (p<0.001)., Conclusions: This study identified four homogenous groups of patients with APS listed as: i) cardiovascular and arterial risk, ii) obstetrical, iii) VTE and microvascular, and iv) ANA-positive APS. We found that ANA-positivity was associated with higher rates of relapse. Applying ANA status to classification criteria could constitute a novel approach to tailoring management for APS, based on phenotypic patterns and risk assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ottavi, Toulon, Casolla and Martis.)
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- 2024
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35. Unmasking the invisible enemy: A case report of metagenomics-guided diagnosis and treatment of neonatal septic meningitis caused by Corynebacterium aurimucosum in a preterm infant with neonatal lupus erythematosus.
- Author
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Xia Q, Gu M, Xu Y, Sang H, Lin W, Wang Y, and Liu K
- Subjects
- Infant, Male, Female, Infant, Newborn, Humans, Infant, Premature, Antibodies, Antinuclear, Bacteria, Premature Birth, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic congenital, Meningitis, Corynebacterium
- Abstract
Rationale: Neonatal septic meningitis is a serious condition that can be caused by various pathogens, including Corynebacterium aurimucosum, a rare and opportunistic bacterium. We reports a case of infectious meningitis in a premature infant with neonatal lupus erythematosus caused by C aurimucosum. The purpose of this study is to explore the occurrence of meningitis caused by C aurimucosum in preterm infants with neonatal lupus erythematosus. We found that early diagnosis and treatment are crucial for this type of meningitis, especially for infants with impaired immunity or mothers receiving immunosuppressive therapy. This bacterium is rare in clinical practice, but it needs to be taken seriously., Patient Concerns: The infant was born to a mother with systemic lupus erythematosus who had a history of long-term immunosuppressive therapy. The infant presented with preterm birth, purplish-red skin, fever, and widespread scarlet dermatitis. He also had positive anti-Ro/SSA and anti-La/SSB antibodies., Diagnosis: The infant was diagnosed with neonatal lupus erythematosus based on clinical and serological features. A lumbar puncture revealed septic meningitis with high levels of total nucleated cells, protein, and Pan's test in the CSF. The macrogenic examination identified C aurimucosum as the causative agent. The culture of the mother's vaginal secretion also revealed the same bacterium., Interventions: The infant was treated with anti-infective therapy with ceftriaxone, ampicillin, vancomycin, and meropenem. He also received prednisone and gammaglobulin infusion for neonatal lupus erythematosus., Outcomes: The infant's temperature returned to normal, and his general condition and responsiveness improved. The CSF cytology and biochemistry normalized, and the culture was negative. The cranial MRI examination showed no abnormalities. The red rash disappeared, and the follow-ups after discharge revealed no complications., Lessons: This case highlights the importance of early diagnosis and treatment of neonatal septic meningitis caused by C aurimucosum, especially in infants with immunocompromised conditions or maternal history of immunosuppressive therapy. C aurimucosum should not be overlooked as a potential pathogen in neonatal septic meningitis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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36. Are Aptamers Really Promising as Receptors for Analytical Purposes? Insights into Anti-Lysozyme DNA Aptamers through a Multitechnique Study.
- Author
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Toma L, Mattarozzi M, Ronda L, Marassi V, Zattoni A, Fortunati S, Giannetto M, and Careri M
- Subjects
- Muramidase, Reproducibility of Results, SELEX Aptamer Technique methods, Antibodies, Antinuclear, Aptamers, Nucleotide chemistry
- Abstract
Aptamers are recognition elements increasingly used for the development of biosensing strategies, especially in the detection of proteins or small molecule targets. Lysozyme, which is recognized as an important biomarker for various diseases and a major allergenic protein found in egg whites, is one of the main analytical targets of aptamer-based biosensors. However, since aptamer-based strategies can be prone to artifacts and data misinterpretation, rigorous strategies for multifaceted characterization of the aptamer-target interaction are needed. In this work, a multitechnique approach has been devised to get further insights into the binding performance of the anti-lysozyme DNA aptamers commonly used in the literature. To study molecular interactions between lysozyme and different anti-lysozyme DNA aptamers, measurements based on a magneto-electrochemical apta-assay, circular dichroism spectroscopy, fluorescence spectroscopy, and asymmetrical flow field-flow fractionation were performed. The reliability and versatility of the approach were proved by investigating a SELEX-selected RNA aptamer reported in the literature, that acts as a positive control. The results confirmed that an interaction in the low micromolar range is present in the investigated binding buffers, and the binding is not associated with a conformational change of either the protein or the DNA aptamer. The similar behavior of the anti-lysozyme DNA aptamers compared to that of randomized sequences and polythymine, used as negative controls, showed nonsequence-specific interactions. This study demonstrates that severe testing of aptamers resulting from SELEX selection is the unique way to push these biorecognition elements toward reliable and reproducible results in the analytical field.
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- 2024
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37. Duplex Vertical-Flow Rapid Tests for Point-of-Care Detection of Anti-dsDNA and Anti-Nuclear Autoantibodies.
- Author
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Lei R, Arain H, Wang D, Arunachalam J, Saxena R, and Mohan C
- Subjects
- Humans, Antibodies, Antinuclear, Point-of-Care Systems, Enzyme-Linked Immunosorbent Assay, Autoantibodies, Lupus Erythematosus, Systemic diagnosis
- Abstract
The goal of this study is to develop a rapid diagnostic test for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HCs). Observer scores and absolute signal intensities from the VFA were validated via ELISA. The rapid point-of-care VFA test that was engineered demonstrated a limit of detection of 0.5 IU/mL for ANA and αDNA autoantibodies in human plasma with an inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in SLE and HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and an 84% ROC AUC value in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease, and rapid turnaround, it can also be used to assess SLE prevalence estimates.
- Published
- 2024
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38. DFS70 Autoantibodies: Clinical Utility in Antinuclear Antibody Testing.
- Author
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Bossuyt X
- Subjects
- Female, Humans, Antibodies, Antinuclear, Autoantibodies, Enzyme-Linked Immunosorbent Assay, Transcription Factors, Male, Autoimmune Diseases diagnosis, Rheumatic Diseases diagnosis
- Abstract
Background: Screening for antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cells is helpful for the diagnosis and classification of ANA-associated rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome, mixed connective tissue disease, systemic sclerosis, and inflammatory myopathies. The dense fine speckled (DFS) pattern is a special HEp-2 IIF pattern (produced by anti-DFS70 antibodies) because it is not associated with a specific medical condition and therefore can obfuscate interpretation., Content: In this paper, detection methods for and clinical associations of anti-DFS70 antibodies are reviewed., Summary: The target antigen of the antibodies that cause the DFS pattern is a 70 kDa protein (DFS70). Commercial methods that detect antibodies to full-length or truncated DFS70 are available for use in clinical laboratories (ELISA, chemiluminescence, dot/line blot). Anti-DFS70 can be found in (apparently) healthy individuals (with a higher frequency in young individuals and in females), in several (inflammatory) conditions and in malignancy. There is no clinical association that is well-established. Special attention (and critical reflection) is given to the observation that monospecific anti-DFS70 (i.e., in the absence of antibodies that are linked to ANA-associated rheumatic diseases) is rarely found in ANA-associated rheumatic diseases., (© Association for Diagnostics & Laboratory Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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39. Autoimmune Hepatitis: Epidemiology, Subtypes, and Presentation.
- Author
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Shiffman ML
- Subjects
- Humans, Autoantibodies, Antibodies, Antinuclear, Hepatitis, Autoimmune diagnosis, Hepatitis, Autoimmune epidemiology
- Abstract
Autoimmune hepatitis (AIH) is a chronic immunologic disorder in which the immune system targets the liver. The disease has a genetic basis and this accounts for the epidemiologic variation observed in serologic testing and clinical presentation across different populations. The incidence of AIH increases with age into the 70s and seems to be increasing in prevalence. Most patients test positive for antinuclear antibody, ASMA, or anti-LKM but about 20% of patients do not have these serologic markers. At clinical presentation, patients may be asymptomatic, symptomatic, have acute liver failure, or decompensated cirrhosis., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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40. The greatest contribution to medical science is the transformation from studying symptoms to studying their causes-the unrelenting legacy of Robert Koch and Louis Pasteur-and a causality perspective to approach a definition of SLE.
- Author
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Rekvig OP
- Subjects
- Humans, Antibodies, Antinuclear, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic etiology, Autoimmune Diseases, Communicable Diseases
- Abstract
The basic initiative related to this study is derived from the fact that systemic lupus erythematosus (SLE) is a unique and fertile system science subject. We are, however, still far from understanding its nature. It may be fair to indicate that we are spending more time and resources on studying the complexity of classified SLE than studying the validity of classification criteria. This study represents a theoretical analysis of current instinctual SLE classification criteria based on "the causality principle." The discussion has its basis on the radical scientific traditions introduced by Robert Koch and Louis Pasteur. They announced significant changes in our thinking of disease etiology through the implementation of the modern version of "the causality principle." They influenced all aspects of today's medical concepts and research: the transformation of medical science from studies of symptoms to study their causes , relevant for monosymptomatic diseases as for syndromes. Their studies focused on bacteria as causes of infectious diseases and on how the immune system adapts to control and prevent contagious spreading. This is the most significant paradigm shift in the modern history of medicine and resulted in radical changes in our view of the immune system. They described acquired post-infection immunity and active immunization by antigen-specific vaccines . The paradigm "transformation" has a great theoretical impact also on current studies of autoimmune diseases like SLE: symptoms and their cause(s) . In this study, the evolution of SLE classification and diagnostic criteria is discussed from "the causality principle" perspective, and if contemporary SLE classification criteria are as useful as believed today for SLE research. This skepticism is based on the fact that classification criteria are not selected based on cogent causal strategies . The SLE classification criteria do not harmonize with Koch's and Pasteur's causality principle paradigms and not with Witebsky's Koch-derived postulates for autoimmune and infectious diseases. It is not established whether the classification criteria can separate SLE as a "one disease entity" from "SLE-like non-SLE disorders"-the latter in terms of SLE imitations. This is discussed here in terms of weight, rank, and impact of the classification criteria: Do they all originate from "one basic causal etiology"? Probably not., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rekvig.)
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- 2024
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41. Naomi Rothfield, MD, MACR: A Giant Gift in a Small Package.
- Author
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Weinstein A
- Subjects
- Female, Humans, Antibodies, Antinuclear, Lupus Erythematosus, Systemic diagnosis
- Abstract
Naomi Rothfield was truly a pied piper of lupus. She had an abiding interest in the characterization and clinical significance of antinuclear antibodies and anti-DNA antibodies in the serum of systemic lupus erythematosus (SLE) patients. She described the use of serum complement in SLE diagnosis and the association of inherited complement deficiencies with SLE. Under her leadership, numerous professionals focused their clinical and research activities to benefit lupus patients. Naomi was also instrumental in establishing a lupus group to assist lupus patients, which became one of the founding chapters of the Lupus Foundation of America., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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42. Expanding the role of chromosomal microarray analysis in the evaluation of recurrent pregnancy loss.
- Author
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Eliwa J, Papas RS, and Kutteh WH
- Subjects
- Pregnancy, Female, Humans, Aneuploidy, Microarray Analysis, Antibodies, Antinuclear, Abortion, Habitual diagnosis, Abortion, Habitual genetics, Antiphospholipid Syndrome complications
- Abstract
Multiple factors contribute to recurrent pregnancy loss (RPL). This review highlights the latest international guidelines for RPL workup, including immunological testing, by the American Society for Reproductive Medicine (ASRM), the European Society of Human Reproduction and Embryology (ESHRE), and the Royal College of Obstetricians and Gynaecologists (RCOG). These three societies recommend testing for antiphospholipid syndrome. ESHRE and RCOG also recommend thyroid peroxidase antibody testing, whereas ASRM does not. All guidelines advise against testing of natural killer cells, cytokines, antinuclear antibodies, human leukocyte antigen (HLA) compatibility, anti-HLA antibodies, and anti-sperm antibodies. However, when following ASRM, ESHRE or RCOG diagnostic guidelines, over 50% of cases have no identifiable cause. Genetic testing of products of conception (POC) can improve our understanding of unexplained RPL as aneuploidy is a common cause of RPL. Based on studies reporting results from chromosomal microarray analysis (CMA) of POC, we propose a novel algorithm for RPL evaluation. The algorithm involves following evidence-based societal guidelines (published by ASRM, ESHRE, or RCOG), excluding parental karyotyping, in combination with CMA testing of miscarriage tissue. When utilizing this new evaluation algorithm, the number of unexplained cases of RPL decreases from over 50% to less than 10%. As a result, most patients are provided an explanation for their loss and healthcare costs are potentially reduced. Patients with an otherwise negative workup with euploid POC, are classified as "truly unexplained RPL". These patients are excellent candidates for enrollment in randomized, controlled trials examining novel immunological testing and treatment protocols., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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43. Harmonization of ANA testing challenge: quantification strategy to accurately predict end-point titers avoiding serial dilution.
- Author
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Carbone T, Pafundi V, Ciardo V, Infantino M, Muscella A, and D'Angelo S
- Subjects
- Fluorescent Antibody Technique, Indirect methods, Cytoplasm, Antibodies, Antinuclear
- Abstract
Despite the advantages of automated systems for antinuclear antibody (ANA) analysis, the prediction of end-point titers avoiding serial dilutions is still in progress. The aims of this study were to set a conversion table providing discriminant ranges of fluorescence signal intensity values (FI) corresponding to the end-point titers and validate this tool in a real-life laboratory setting. Eight hundred ninety-four serum samples were analyzed for ANA using Image Navigator System. In order to classify FI into non-overlapping groups corresponding to conventional end-point titers, statistical discriminant analysis was used. Validation study was performed calculating agreement and error rates between visual readings and conversion table of 1119 routine ANA positive samples. Setting of FI ranges corresponding to the end-point titers for different staining patterns was computed. For samples showing single pattern, the overall agreement between visual readings and conversion table was 98.4% for all titers ranging from 1:160 to 1:2560, of which 68.0% had the same titer and 30.4% were within ± one titer difference. Concordance rates according to ANA patterns were as follows: (1) nuclear 98.4%, of which 67.0% had the same titer and 31.4% ± one titer; (2) cytoplasmic 100%, of which 72.7% had the same titer and 27.3% than ± one titer; (3) mitotic 66.6%, of which 33.3% had more ± one titer. Our study developed a quantification method for autoantibodies titers assessment based on just one single sample dilution instead of traditional serial dilution approach, providing significant advantages in routine laboratory in terms of reduction in hand-on time and harmonization of results., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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- View/download PDF
44. SMART-SLE: serology monitoring and repeat testing in systemic lupus erythematosus-an analysis of anti-double-stranded DNA monitoring.
- Author
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Yeo AL, Kandane-Rathnayake R, Koelmeyer R, Golder V, Louthrenoo W, Chen YH, Cho J, Lateef A, Hamijoyo L, Luo SF, Wu YJ, Navarra SV, Zamora L, Li Z, An Y, Sockalingam S, Katsumata Y, Harigai M, Hao Y, Zhang Z, Basnayake BMDB, Chan M, Kikuchi J, Takeuchi T, Bae SC, Oon S, O'Neill S, Goldblatt F, Ng KPL, Law A, Tugnet N, Kumar S, Tee C, Tee M, Ohkubo N, Tanaka Y, Lau CS, Nikpour M, Hoi A, Leech M, and Morand EF
- Subjects
- Humans, DNA, Data Collection, Hematologic Tests, Antibodies, Antinuclear, Lupus Erythematosus, Systemic
- Abstract
Objective: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive., Methods: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare., Results: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009)., Conclusion: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
- Published
- 2024
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45. Clinical algorithm model based on cfDNA to predict SLE disease activity.
- Author
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Wang F, Liu YJ, Miao HB, and Chen Z
- Subjects
- Humans, Biomarkers, Antibodies, Antinuclear, Nucleosomes, Lupus Erythematosus, Systemic, Cell-Free Nucleic Acids
- Abstract
Background: Circulating cell-free DNA (cfDNA) has been widely used as a new liquid-biopsy marker. Dysregulation of cfDNA has been found in patients with systemic lupus erythematosus (SLE). However, the detailed association between cfDNA and SLE has not been thoroughly studied., Methods: Plasma samples were collected from 88 patients with active SLE and 39 patients with inactive SLE. The cfDNA concentration was determined, and the length and distribution of cfDNA fragments were verified., Results: cfDNA concentrations were significantly higher in patients with active SLE than in patients with inactive SLE (0.4 [0.18-0.897] ng/µL vs 0.249 [0.144-0.431] ng/µL; p = .043). cfDNA fragments were enriched in the ranges of 153-198 bp and 300-599 bp. cfDNA concentrations were associated with the reduction of the anti-double-stranded DNA (dsDNA) antibodies titer (r = -0.301, p = .034). The presence of anti-U1 ribonucleoprotein ( p = .012), anti-Sjogren syndrome A ( p = .024), anti-dsDNA ( p = .0208), and anti-nucleosome antibodies ( p = .0382) might associate to the variation of cfDNA concentration. Reduced cfDNA concentration was associated with renal damage in active SLE patients (0.31 [0.11-0.73] ng/µL vs 0.65 [0.27-1.53] ng/µL; p = .009). The Active index, a combination model including cfDNA concentration and other clinical indices, had an area of 0.886 under the receiver operating characteristics curve for distinguishing active SLE. The Active index was positively correlated with the SLE disease activity index score (r = 0.6724, p < .0001)., Conclusions: Through systematic stratified analysis and clinical algorithm model, this study found that plasma cfDNA concentration is closely related to SLE disease severity, which has guiding significance for the future clinical application of cfDNA in SLE., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2024
- Full Text
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46. A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile.
- Author
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Lindelöf L, Rantapää-Dahlqvist S, Lundtoft C, Sandling JK, Leonard D, Sayadi A, Rönnblom L, Enocsson H, Sjöwall C, Jönsen A, Bengtsson AA, Hong MG, Diaz-Gallo LM, Bianchi M, Kozyrev SV, Lindblad-Toh K, Nilsson Ekdahl K, Nilsson B, Gunnarsson I, Svenungsson E, and Eriksson O
- Subjects
- Humans, Antibodies, Antinuclear, Autoantibodies, Complement System Proteins, Ficolins, Lectins genetics, Hematologic Diseases, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic epidemiology, Lupus Erythematosus, Systemic genetics, Lymphopenia
- Abstract
The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin-3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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47. Systemic sclerosis patients with negative antinuclear antibodies have distinctive clinical manifestations: a multicenter CRDC cohort in China.
- Author
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Hui M, Wang X, Zhou J, Zhang L, Duan X, Li M, Wang Q, Zhao J, Hou Y, Xu D, and Zeng X
- Subjects
- Male, Humans, Antibodies, Antinuclear, China epidemiology, Asian People, Scleroderma, Systemic diagnosis, Scleroderma, Systemic epidemiology, Scleroderma, Systemic complications, Lung Diseases, Interstitial
- Abstract
Background: The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc)., Objective: A variety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in a Chinese Rheumatism Data Center (CRDC) multicenter cohort in China., Methods: Patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs., Results: Antinuclear antibodies were detected in 2129 of 2809 patients enrolled in the study; 4.2% of patients were negative. There were more males among ANA-negative SSc patients (29/60 vs. 294/1746, p < 0.001). The incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs. 18.5%, p = 0.002), interstitial lung disease (65.2% vs. 77.9%, p = 0.015), and pulmonary arterial hypertension (11.5% vs. 29.0%, p = 0.006) was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal erythrocyte sedimentation rate (32.4% vs. 47.6%, p = 0.013) and IgG elevation (14.3% vs. 37.0%, p = 0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients., Conclusion: Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2024
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48. Anti-SS-A antibody is a potential predictor of severe Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study.
- Author
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Watanabe Y, Watanabe T, and Yamaguchi Y
- Subjects
- Humans, Retrospective Studies, Antibodies, Antinuclear, Stevens-Johnson Syndrome diagnosis
- Abstract
Competing Interests: Conflicts of interest None disclosed.
- Published
- 2024
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49. Autoimmune Markers in Primary Biliary Cholangitis.
- Author
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Shah SK and Bowlus CL
- Subjects
- Humans, Autoantibodies, Antibodies, Antinuclear, Biomarkers, Liver Cirrhosis, Biliary diagnosis, Cholestasis, Cholangitis diagnosis
- Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The most common antibody associated with PBC is the anti-mitochondrial antibody (AMA), present in 90% to 95% of patients. For patients who are AMA-negative, novel biomarkers, such as antinuclear antibody-specific antibodies Sp100 and gp210 and anti-kelch-like-12 and anti-hexokinase-1 antibodies, may further aid in the diagnosis of PBC. Several laboratory methods, including immunofluorescence, enzyme-linked immunosorbent assay, immunoblotting, and bead-based assays, exist to evaluate for the presence of antibodies. This article describes various methods used to evaluate antibodies as well as describe the antibodies present in PBC., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
50. Antinuclear matrix protein 2 antibody-positive dermatomyositis: a rare entity.
- Author
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Zussino M, Maronese CA, Montanelli G, Boggio FL, Moltrasio C, Cattaneo A, Marzano AV, and Genovese G
- Subjects
- Humans, Antibodies, Antinuclear, Dermatomyositis diagnosis, Leukocyte Disorders
- Published
- 2024
- Full Text
- View/download PDF
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