scholarly journals A case of ANCA-associated vasculitis presenting de novo in pregnancy, successfully treated with rituximab

2018 ◽  
Vol 13 (1) ◽  
pp. 41-44 ◽  
Author(s):  
A Pefanis ◽  
DS Williams ◽  
H Skrzypek ◽  
A Fung ◽  
K Paizis
Keyword(s):  
De Novo ◽  
Clinical Manifestations ◽  
Significant Morbidity ◽  
Pathogenic Role ◽  
Disease Pathogenesis ◽  
Anca Vasculitis ◽  
Anca Associated Vasculitis ◽  
In Pregnancy ◽  
New Onset

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are rare small vessel vasculitides of unknown cause. The pathogenic role of MPO-ANCA in the vasculitides has been supported using various animal models, with B-cells playing a role in the disease pathogenesis. Pregnancy in the presence of an autoimmune disease such as vasculitis is often associated with significant morbidity. Little is known about the outcomes when women present with de novo vasculitis during pregnancy, and the appropriate management of such presentations is unclear. We describe a case of a 33-year-old female presenting in her second pregnancy with new onset ANCA vasculitis at 12 weeks’ gestation. She was successfully treated with prednisolone and rituximab, and delivered a healthy 2.8 kg boy at 36 weeks’ gestation with no clinical manifestations of vasculitis or neutropenia in the neonate.

scholarly journals Antineutrophil Cytoplasmic Autoantibodies Interact with Primary Granule Constituents on the Surface of Apoptotic Neutrophils in the Absence of Neutrophil Priming

1996 ◽  
Vol 184 (6) ◽  
pp. 2231-2242 ◽  
Author(s):  
Hannah M. Gilligan ◽  
Brunel Bredy ◽  
Hugh R. Brady ◽  
Marie-Josée Hébert ◽  
Henry S. Slayter ◽  
...  
Keyword(s):  
Cell Surface ◽  
Intact Cell ◽  
Immunogold Labeling ◽  
Pathogenic Role ◽  
Anca Associated Vasculitis ◽  
Antineutrophil Cytoplasmic Autoantibodies ◽  
Neutrophil Priming ◽  
Gain Access ◽  
Primary Granule

The pathogenic role of antineutrophil cytoplasmic autoantibodies (ANCA) remains controversial because of the difficulty in explaining how extracellular ANCA can interact with intracellular primary granule constituents. It has been postulated that cytokine priming of neutrophils (PMN), as may occur during a prodromal infection, is an important trigger for mobilization of granules to the cell surface, where they may interact with ANCA. We show by electron microscopy that apoptosis of unprimed PMN is also associated with the translocation of cytoplasmic granules to the cell surface and alignment just beneath an intact cell membrane. Immunofluorescent microscopy and FACS® analysis demonstrate reactivity of ANCA-positive sera and antimyeloperoxidase antibodies with apoptotic PMN, but not with viable PMN. Moreover, we show that apoptotic PMN may be divided into two subsets, based on the presence or absence of granular translocation, and that surface immunogold labeling of myeloperoxidase occurs only in the subset of PMN showing translocation. These results provide a novel mechanism that is independent of priming, by which ANCA may gain access to PMN granule components during ANCA-associated vasculitis.

P.040 New-onset secondary hormone deficiency in patients with incidental versus clinically manifesting sellar masses

2018 ◽  
Vol 45 (s2) ◽  
pp. S26-S26
Author(s):  
N Vaninetti ◽  
S Mustafa ◽  
S Doucette ◽  
R Glasgow ◽  
L Tramble ◽  
...  
Keyword(s):  
Tumour Size ◽  
Clinical Manifestations ◽  
Hormone Deficiency ◽  
Significant Morbidity ◽  
Hormonal Function ◽  
Nonsurgical Patients ◽  
Incidental Lesions ◽  
New Onset

Background: Secondary hormonal deficiency (SHD) in patients with sellar masses (SM) is associated with significant morbidity. Purpose: to compare long-term risk of new-onset SHD in SM found incidentally (ISM) versus those clinically manifesting (CMSM). Methods: From the Halifax Neuropituitary Program’s database, we identified all patients having non-functioning and non-pituitary SM from January 1, 2006, with ≥ 12 months follow-up. Results: There were 214 CMSM (108 with baseline SHD) and 148 ISM (37 with baseline SHD) patients (mean follow-up: 5.7 and 5.0 years, respectively). In patients who underwent early surgery (<90 days from diagnosis), 3-month post-op hormonal function was considered baseline. Despite unchanged tumour size in over 95%, 129 (35.6%) developed new-onset SHD at up to 120 months. The risk of developing new-onset SHD was similar in CMSM and ISM groups (HR = 1.10; CI= 0.69-1.75; p= 0.7), and in surgical and nonsurgical patients (HR=1.24; CI= 0.59-2.61; p = 0.58). Conclusions: More than one third of patients with non-functioning or non-pituitary SM, presenting either with clinical manifestations or as incidental lesions, will develop new-onset SHD. Furthermore, SHD may develop several years later and despite stability of tumors, highlighting the need for ongoing, long-term hormonal assessment.

scholarly journals New-onset IgG autoantibodies in hospitalized patients with COVID-19

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah Esther Chang ◽  
Allan Feng ◽  
Wenzhao Meng ◽  
Sokratis A. Apostolidis ◽  
Elisabeth Mack ◽  
...  
Keyword(s):  
De Novo ◽  
Significant Proportion ◽  
Connective Tissue Diseases ◽  
Clinical Manifestations ◽  
Structural Proteins ◽  
Rare Disorders ◽  
Autoantibody Production ◽  
Wide Range ◽  
Pathogenic Viruses ◽  
New Onset

AbstractCOVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.

scholarly journals How pancreatic adenocarcinoma might cause diabetes? The role of TGF- β

2021 ◽  
pp. 05-10
Author(s):  
Hanan F. Aly
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Pancreatic Adenocarcinoma ◽  
De Novo ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Β Cells ◽  
Selective Depletion ◽  
New Onset

Pancreatic ductal adenocarcinoma (PDAC) is a deadly sickness that stays incurable due to past due diagnosis, which renders any healing intervention challenging. Most PDAC sufferers expand de novo diabetes, which exacerbates their morbidity and mortality. How PDAC triggers diabetes continues to be unfolding. Using a mouse version of KrasG12D-pushed PDAC, which faithfully recapitulates the development of the human sickness, we determined a large and selective depletion of β-cells, taking place very early on the degrees of preneoplastic lesions. Mechanistically, it turned into observed that accelerated TGF beta (TGF-β) signaling throughout PDAC development induced erosion of β-mobileular mass thru apoptosis. Suppressing TGF-β signaling, both pharmacologically thru TGF-β immunoneutralization or genetically thru deletion of Smad4 or TGF-β kind II receptor (TβRII), afforded size able safety in opposition to PDAC-pushed β-mobileular depletion. From a translational perspective, each activation of TGF-β signaling and depletion of β-cells often arise in human PDAC, imparting a mechanistic cause of the pathogenesis of diabetes in PDAC sufferers, and similarly implicating new- onset diabetes as a capability early prognostic marker for PDAC. In this mini review we try to analyze the principle relationships between pancreatic cancer and diabetes and vice versa in addition to the implication of TGF-β signaling as a likely goal for attenuating diabetes in pancreatic most cancers patients.

scholarly journals Promising diagnostic tools for endometriosis given the pathogenic role of genetic factors

2021 ◽  
Vol 4 (1) ◽  
pp. 12-16
Author(s):  
G.A. Ikhtiyarova ◽  
◽  
M.Zh. Aslonova ◽  
Z.Sh. Kurbanova ◽  
D.M. Kalimatova ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Clinical Manifestations ◽  
Hormonal Treatment ◽  
Diagnostic Tools ◽  
Pathogenic Role ◽  
Endometrial Cells ◽  
Keywords Endometriosis ◽  
Depth Study ◽  
Diagnostic Modalities

This paper discusses promising diagnostic modalities for endometriosis considering current ideas about the role of genetic factors in the pathogenesis of this condition. The hypotheses on pathogenesis and modern diagnostic approaches are addressed. The authors uncover the issues of genetic predisposition to endometriosis. The inhibition of tumor suppressor genes (CDKN2B, CDKN2 A, and ARF) and the activation of genes of early (embryonic) development of the female reproductive system (HOXA, HOXB, WNT4) lead to endometrial metaplasia. As a result, endometrial cells gain the ability to proliferate. The role of microRNA in the impaired regulation of the methylation of various genes associated with endometriosis is described. These factors specifically affect the course and clinical manifestations of endometriosis. Certain key proteins involved in the pathogenesis of endometriosis and whose synthesis is controlled by microRNA may be regarded as the diagnostic markers of endometriosis. Their in-depth study will identify novel therapeutic targets and promote the development of new non-hormonal treatment approaches to endometriosis. KEYWORDS: endometriosis, proliferation, endometrium, genes, polymorphism, diagnostic, epigenetics, microRNA. FOR CITATION: Ikhtiyarova G.A., Aslonova M.Zh., Kurbanova Z.Sh., Kalimatova D.M. Promising diagnostic tools for endometriosis given the pathogenic role of genetic factors. Russian Journal of Woman and Child Health. 2021;4(1):12–16. DOI: 10.32364/2618-8430- 2021-4-1-12-16.

B-cell treatment in ANCA-associated vasculitis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_3) ◽  
pp. iii68-iii73
Author(s):  
Alexandre Karras ◽  
Hélène Lazareth ◽  
Sophie Chauvet
Keyword(s):  
B Cells ◽  
B Cell ◽  
Optimal Dose ◽  
B Cell Depletion ◽  
Anca Vasculitis ◽  
Anca Associated Vasculitis ◽  
Cell Subpopulations ◽  
Anti Cd20

Abstract The pivotal role of B-cells in ANCA-associated vasculitis has been suggested by experimental data that demonstrate the direct pathogenicity of ANCAs. Rituximab (RTX), an anti-CD20 monoclonal antibody that targets B-cells, has proven its efficacy for induction of remission in severe ANCA vasculitis. RTX is equivalent to CYC for induction of remission, and is probably superior in relapsing patients. Long-term B cell depletion by prolonged RTX treatment has been shown to significantly reduce the relapse rate, when compared with AZA maintenance therapy. Biomarkers, such as B-cell subpopulations or ANCA monitoring, may help the clinician to determine the optimal dose and duration of RTX therapy.

scholarly journals Exome-Based Case-Control Analysis Highlights the Pathogenic Role of Ciliary Genes in Transposition of the Great Arteries

2020 ◽  
Vol 126 (7) ◽  
pp. 811-821 ◽  
Author(s):  
Xuanyu Liu ◽  
Wen Chen ◽  
Wenke Li ◽  
James R. Priest ◽  
Yuanyuan Fu ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Clinical Characteristics ◽  
Congenital Heart ◽  
De Novo ◽  
Ductus Arteriosus ◽  
Compound Heterozygous ◽  
Control Analysis ◽  
Pathogenic Role ◽  
Polygenic Inheritance

Rationale: Transposition of the great arteries (TGA) is one of the most severe types of congenital heart diseases. Understanding the clinical characteristics and pathogenesis of TGA is, therefore, urgently needed for patient management of this severe disease. However, the clinical characteristics and genetic cause underlying TGA remain largely unexplored. Objective: We sought to systematically examine the clinical characteristics and genetic cause for isolated nonsyndromic TGA. Methods and Results: We recruited 249 patients with TGA (66 family trios) and performed whole-exome sequencing. The incidence of patent ductus arteriosus in dextro-TGA (52.7%) and dextrocardia/mesocardia in congenitally corrected TGA (32.8%) were significantly higher than that in other subtypes. A high prevalence of bicuspid pulmonic valve (9.6%) was observed in patients with TGA. Similar results were observed in a replication group of TGA (n=132). Through a series of bioinformatics filtering steps, we obtained 82 candidate genes harboring potentially damaging de novo, loss of function, compound heterozygous, or X-linked recessive variants. Established congenital heart disease–causing genes, such as FOXH1 , were found among the list of candidate genes. A total of 19 ciliary genes harboring rare potentially damaging variants were also found; for example, DYNC2LI1 with a de novo putatively damaging variant. The enrichment of ciliary genes supports the roles of cilia in the pathogenesis of TGA. In total, 33% of the TGA probands had >1 candidate gene hit by putatively deleterious variants, suggesting that a portion of the TGA cases were probably affected by oligogenic or polygenic inheritance. Conclusions: The findings of clinical characteristic analyses have important implications for TGA patient stratification. The results of genetic analyses highlight the pathogenic role of ciliary genes and a complex genetic architecture underlying TGA.

scholarly journals Neurocysticercosis in Pregnancy

2018 ◽  
Vol 08 (02) ◽  
pp. e51-e56 ◽  
Author(s):  
Camille Webb ◽  
Mauricio Rosa ◽  
Gayle Olson ◽  
Miguel Cabada
Keyword(s):  
Differential Diagnosis ◽  
Postpartum Period ◽  
Demographic Data ◽  
Clinical Manifestations ◽  
Clinical Findings ◽  
Patient Demographic ◽  
Patient Demographic Data ◽  
Exposure History ◽  
In Pregnancy ◽  
New Onset

AbstractThe normal physiologic changes during pregnancy contribute to nutritional, metabolic, and immunologic adjustments, which can have an impact on the presentation of several diseases. New onset seizures during pregnancy and the postpartum can be attributed to several etiologies. Patient demographic data as well as personal and social histories are key in determining the etiology of new onset seizures. Neurocysticercosis (NCC), a commonly overlooked etiology, must be included in the differential diagnosis of patients with new onset seizures coming from NCC endemic areas. The diagnosis is based on a combination of clinical findings, exposure history, imaging, and serology. We present two cases of patients with NCC that became symptomatic during pregnancy or postpartum period. We will review the epidemiology, clinical manifestations, and management of NCC in pregnancy.

Pathogenesis of Wegener's granulomatosis: current concepts

2005 ◽  
Vol 7 (8) ◽  
pp. 1-19 ◽  
Author(s):  
Pasha Sarraf ◽  
Michael C. Sneller
Keyword(s):  
Animal Models ◽  
Wegener’S Granulomatosis ◽  
Granulomatous Inflammation ◽  
Wegener's Granulomatosis ◽  
Small Vessel Vasculitis ◽  
Focused Attention ◽  
Pathogenic Role ◽  
Disease Pathogenesis ◽  
Autoimmune Syndrome

Wegener's granulomatosis (WG) is a complex autoimmune syndrome that is characterised by upper/lower respiratory necrotising granulomatosis, glomerulonephritis and small-vessel vasculitis. Since Wegener's 1936 description, considerable advances in recognition and treatment have changed this disease from a rapidly and uniformly fatal illness to a chronic disease characterised by remissions and relapses. The serendipitous discovery of anti-neutrophil cytoplasmic antibodies (ANCAs) as a marker associated with WG focused attention on the potential pathogenic role of these antibodies and has recently led to the development of novel animal models that might facilitate our understanding of the disease pathogenesis. Future animal models of this disease will have to account for the role of both ANCA-mediated pathology and granulomatous inflammation to enable us to understand the chronic and persistent features of WG in humans.

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