12 results on '"Sethi, Sidharth Kumar"'
Search Results
2. Complement Inhibition in Severe S. pneumoniae-Associated Hemolytic Uremic Syndrome.
- Author
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Sethi SK, Raina R, Dhaliwal M, Raghunathan V, Bansal SB, Taneja S, and Bagga A
- Subjects
- Humans, Complement System Proteins, Hemolytic-Uremic Syndrome drug therapy, Pneumonia
- Published
- 2023
- Full Text
- View/download PDF
3. Overall neutralization of complement factor H by autoantibodies in the acute phase of the autoimmune form of atypical hemolytic uremic syndrome.
- Author
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Blanc C, Roumenina LT, Ashraf Y, Hyvärinen S, Sethi SK, Ranchin B, Niaudet P, Loirat C, Gulati A, Bagga A, Fridman WH, Sautès-Fridman C, Jokiranta TS, Frémeaux-Bacchi V, and Dragon-Durey MA
- Subjects
- Acute Disease, Adult, Autoimmune Diseases diagnosis, Autoimmune Diseases pathology, Child, Complement C3 metabolism, Complement Factor H metabolism, Hemolytic-Uremic Syndrome diagnosis, Hemolytic-Uremic Syndrome pathology, Humans, Protein Binding immunology, Autoantibodies physiology, Autoimmune Diseases immunology, Complement Factor H antagonists & inhibitors, Complement Factor H immunology, Hemolytic-Uremic Syndrome immunology, Neutralization Tests methods
- Abstract
Complement is a major innate immune surveillance system. One of its most important regulators is the plasma protein factor H (FH). FH inactivation by mutations or by autoantibodies is associated with a thrombotic microangiopathy disease, atypical hemolytic uremic syndrome. In this study, we report the characterization of blood samples from 19 anti-FH Ab-positive atypical hemolytic uremic syndrome patients collected at the acute phase of the disease. Analyses of the functional consequences and epitope mapping, using both fluid phase and solid phase approaches, were performed. The anti-FH Abs perturbed FH-mediated cell protection (100%), inhibited FH interaction with C3 (46%), and caused C3 consumption (47%). The Abs were directed against multiple FH epitopes located at the N and C termini. In all tested patients, high titers of FH-containing circulating immune complexes were detected. The circulating immune complex titers correlated with the disease stage better than did the Ab titers. Our results show that anti-FH autoantibodies induce neutralization of FH at acute phase of the disease, leading to an overall impairment of several functions of FH, extending the role of autoantibodies beyond the impairment of the direct cell surface protection.
- Published
- 2012
- Full Text
- View/download PDF
4. Complement evaluation in atypical hemolytic uremic syndrome: current concepts.
- Author
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Sethi SK and Jhaveri KD
- Subjects
- Atypical Hemolytic Uremic Syndrome, Autoantibodies blood, Biomarkers blood, Hemolytic-Uremic Syndrome blood, Humans, Prognosis, Complement Activation, Complement System Proteins metabolism, Hemolytic-Uremic Syndrome immunology
- Published
- 2012
- Full Text
- View/download PDF
5. Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome.
- Author
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Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B, André JL, Takagi N, Cheong HI, Hari P, Le Quintrec M, Niaudet P, Loirat C, Fridman WH, and Frémeaux-Bacchi V
- Subjects
- Adult, Age Factors, Child, Child, Preschool, Cohort Studies, Complement Activation immunology, Female, Follow-Up Studies, Hemolytic-Uremic Syndrome diagnosis, Hemolytic-Uremic Syndrome epidemiology, Humans, Immunoglobulins, Intravenous administration & dosage, Infant, Kidney Transplantation, Male, Middle Aged, Plasma Exchange methods, Risk Assessment, Severity of Illness Index, Sex Factors, Stem Cell Transplantation methods, Time Factors, Treatment Outcome, Autoantibodies immunology, Complement Factor H immunology, Hemolytic-Uremic Syndrome immunology, Hemolytic-Uremic Syndrome therapy
- Abstract
Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy that associates, in 70% of cases, with genetic or acquired disorders leading to dysregulation of the alternative pathway of complement. Autoantibody directed against Factor H causes at least 6% to 10% of aHUS cases, but only a few clinical reports are available. Here, we describe the clinical, biologic, genetic features, treatment, and outcome of 45 patients who presented with aHUS associated with anti-FH autoantibody. We found that this form of aHUS primarily affects children between 9 and 13 years old but it also affects adults. It presents with a high frequency of gastrointestinal symptoms and with extrarenal complications and has a relapsing course. Activation of the alternative pathway of complement at the onset of disease portends a poor prognosis. Early specific treatment may lead to favorable outcomes. These data should improve the recognition and diagnosis of this form of aHUS and help identify patients at high risk of a poor outcome.
- Published
- 2010
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- View/download PDF
6. Anti-factor H autoantibody-associated hemolytic uremic syndrome: review of literature of the autoimmune form of HUS.
- Author
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Dragon-Durey MA, Blanc C, Garnier A, Hofer J, Sethi SK, and Zimmerhackl LB
- Subjects
- Complement C3b Inactivator Proteins genetics, Gene Deletion, Hemolytic-Uremic Syndrome genetics, Hemolytic-Uremic Syndrome therapy, Humans, Immunosuppressive Agents therapeutic use, Plasma Exchange, Autoantibodies immunology, Complement Factor H immunology, Hemolytic-Uremic Syndrome immunology
- Abstract
Non-Shiga toxin-associated hemolytic uremic syndrome (atypical HUS) is a rare form of thrombotic microangiopathy that associates hemolytic anemia, thrombocytopenia, and acute renal failure. The disease has been demonstrated to be linked with a complement alternative pathway dysregulation due to genetic defects but also to development of autoantibodies to factor H (FH), the main plasmatic alternative pathway regulatory protein. In this review, we summarize the more recent data of this autoimmune form of HUS at the level of epidemiology and its clinical and biological features. We propose the performance of anti-FH autoantibodies screening at the very onset of the disease in all cases of HUS to first make the proper diagnosis as early as possible, and second to support an appropriate therapy including early plasma exchanges and immunosuppressive treatments., (© Thieme Medical Publishers.)
- Published
- 2010
- Full Text
- View/download PDF
7. Hemolytic uremic syndrome due to homozygous factor H deficiency.
- Author
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Sethi SK, Marie-Agnes DD, Thaker N, Hari P, and Bagga A
- Subjects
- Base Sequence, Complement C3 genetics, Complement C3 metabolism, Complement C4 genetics, Complement C4 metabolism, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Infant, Kidney pathology, Male, Molecular Sequence Data, Complement Factor H deficiency, Complement Factor H genetics, Hemolytic-Uremic Syndrome etiology, Hemolytic-Uremic Syndrome genetics
- Abstract
The majority of complement factor H mutations associated with atypical hemolytic uremic syndrome (HUS) are heterozygous. Homozygous mutations causing atypical hemolytic uremic syndrome are rare. We report a 7-month-old boy with HUS, severe hypocomplementemia (low C3 and normal C4 levels), and extremely low circulating levels of factor H. Genetic analysis showed homozygous 4 bp deletion in the gene encoding factor H in the patient, with his parents being carriers. The patient showed progression to end-stage renal disease and is presently on chronic ambulatory peritoneal dialysis.
- Published
- 2009
- Full Text
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8. What came first, atypical hemolytic uremic syndrome or malignant hypertension: a clinical dilemma.
- Author
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Sethi, Sidharth Kumar, S, Savita, Nair, Aishwarya, Soni, Kritika, Bihari Bansal, Shyam, Rana, Abhyuday S., and Raina, Rupesh
- Subjects
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HEMOLYTIC-uremic syndrome , *HYPERTENSION , *THROMBOTIC thrombocytopenic purpura , *HYPERTENSIVE crisis , *OPTIC disc edema , *LEFT ventricular hypertrophy , *DILEMMA - Abstract
This article discusses a case study of a 7-year-old girl who presented with a hypertensive crisis and thrombotic microangiopathy (TMA). The study found that severe hypertension led to TMA in this case, which is rare in children. The patient was treated with intravenous eculizumab and antihypertensive agents, which resulted in improvement in her condition. The article emphasizes the importance of evaluating hypertension-associated TMA for complement defects and initiating aggressive hypertension control and targeted therapies for better outcomes. It also highlights the potential association between severe hypertension and TMA, and the role of complement activation in the pathogenesis. [Extracted from the article]
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- 2024
- Full Text
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9. Voice of a caregiver: call for action for multidisciplinary teams in the care for children with atypical hemolytic uremic syndrome.
- Author
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Burke, Linda, Sethi, Sidharth Kumar, Boyer, Olivia, Licht, Christoph, McCulloch, Mignon, Shah, Raghav, Luyckx, Valerie A., and Raina, Rupesh
- Subjects
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HEMOLYTIC-uremic syndrome diagnosis , *HEMOLYTIC-uremic syndrome treatment , *THERAPEUTIC use of monoclonal antibodies , *DISEASE management , *HEMOLYTIC-uremic syndrome , *PSYCHOLOGY of caregivers , *HEALTH promotion , *HEALTH care teams , *CHILDREN - Abstract
An editorial highlights the pressing need for multidisciplinary teams in caring for children with atypical hemolytic uremic syndrome (aHUS). It emphasizes the challenges faced by patients and families due to the rarity and complexity of the disease, leading to delays in accurate diagnosis and treatment. It stresses the importance of prompt and thorough diagnosis, particularly given the urgent therapeutic implications of aHUS.
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- 2024
- Full Text
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10. Atypical Hemolytic-Uremic Syndrome: Genetic Basis, Clinical Manifestations, and a Multidisciplinary Approach to Management.
- Author
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Yerigeri, Keval, Kadatane, Saurav, Mongan, Kai, Boyer, Olivia, Burke, Linda LG, Sethi, Sidharth Kumar, Licht, Christoph, and Raina, Rupesh
- Subjects
HEMOLYTIC-uremic syndrome ,SYMPTOMS ,SHIGELLOSIS ,HEMOLYTIC anemia ,HEMATOPOIETIC stem cells ,MEDICAL care ,PULMONARY hypertension - Abstract
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) defined by the triad of hemolytic anemia, thrombocytopenia, and acute kidney injury. Microthrombi develop in the glomerular capillaries secondary to endothelial damage and exert shear stress on red blood cells, consume platelets, and contribute to renal dysfunction and failure. Per current understanding of pathophysiology, HUS is classified into infectious, secondary, and atypical disease. The most common etiology is infectious sequelae of Shiga toxin-producing Escherichia coli (STEC); other causative organisms include shigella and salmonella. Secondary HUS arises from cancer, chemotherapy, solid organ and hematopoietic stem cell transplant, pregnancy, or autoimmune disorders. Primary atypical hemolytic-uremic syndrome (aHUS) is associated with genetic mutations in complement and complement regulatory proteins. Under physiologic conditions, complement regulators keep the alternative complement system continuously active at low levels. In times of inflammation, mutations in complement-related proteins lead to uncontrolled complement activity. The hyperactive inflammatory state leads to glomerular endothelial damage, activation of the coagulation cascade, and TMA findings. Atypical hemolytic-uremic syndrome is a rare disorder with a prevalence of 2.21 to 9.4 per million people aged 20 years or younger; children between the ages of 0 and 4 are most affected. Multidisciplinary health care is necessary for timely management of its extra-renal manifestations. These include vascular disease of the heart, brain, and skin, pulmonary hypertension and hemorrhage, and pregnancy complications. Adequate screening is required to monitor for sequelae. First-line treatment is the monoclonal antibody eculizumab, but several organ systems may require specialized interventions and coordination of care with sub-specialists. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
11. Anti-factor H antibody and its role in atypical hemolytic uremic syndrome.
- Author
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Raina, Rupesh, Mangat, Guneive, Hong, Gordon, Shah, Raghav, Nair, Nikhil, Abboud, Brian, Bagga, Sumedha, and Sethi, Sidharth Kumar
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HEMOLYTIC-uremic syndrome ,COMPLEMENT factor H ,COMPLEMENT activation ,ACUTE kidney failure ,IMMUNOGLOBULINS ,AUTOIMMUNE diseases - Abstract
Atypical hemolytic uremic syndrome (aHUS) an important form of a thrombotic microangiopathy (TMA) that can frequently lead to acute kidney injury (AKI). An important subset of aHUS is the anti-factor H associated aHUS. This variant of aHUS can occur due to deletion of the complement factor H genes, CFHR1 and CFHR3, along with the presence of anti-factor H antibodies. However, it is a point of interest to note that not all patients with anti-factor H associated aHUS have a CFHR1/R3 deletion. Factor-H has a vital role in the regulation of the complement system, specifically the alternate pathway. Therefore, dysregulation of the complement system can lead to inflammatory or autoimmune diseases. Patients with this disease respond well to treatment with plasma exchange therapy along with Eculizumab and immunosuppressant therapy. Anti-factor H antibody associated aHUS has a certain genetic predilection therefore there is focus on further advancements in the diagnosis and management of this disease. In this article we discuss the baseline characteristics of patients with anti-factor H associated aHUS, their triggers, various treatment modalities and future perspectives. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Pediatric Atypical Hemolytic Uremic Syndrome Advances.
- Author
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Raina, Rupesh, Vijayvargiya, Nina, Khooblall, Amrit, Melachuri, Manasa, Deshpande, Shweta, Sharma, Divya, Mathur, Kashin, Arora, Manav, Sethi, Sidharth Kumar, and Sandhu, Sonia
- Subjects
HEMOLYTIC-uremic syndrome ,COMPLEMENT factor H ,COVID-19 vaccines ,GENETIC mutation ,COMPLEMENT receptors ,AUTOANTIBODIES - Abstract
Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by dysregulation of the alternate pathway. The diagnosis of aHUS is one of exclusion, which complicates its early detection and corresponding intervention to mitigate its high rate of mortality and associated morbidity. Heterozygous mutations in complement regulatory proteins linked to aHUS are not always phenotypically active, and may require a particular trigger for the disease to manifest. This list of triggers continues to expand as more data is aggregated, particularly centered around COVID-19 and pediatric vaccinations. Novel genetic mutations continue to be identified though advancements in technology as well as greater access to cohorts of interest, as in diacylglycerol kinase epsilon (DGKE). DGKE mutations associated with aHUS are the first non-complement regulatory proteins associated with the disease, drastically changing the established framework. Additional markers that are less understood, but continue to be acknowledged, include the unique autoantibodies to complement factor H and complement factor I which are pathogenic drivers in aHUS. Interventional therapeutics have undergone the most advancements, as pharmacokinetic and pharmacodynamic properties are modified as needed in addition to their as biosimilar counterparts. As data continues to be gathered in this field, future advancements will optimally decrease the mortality and morbidity of this disease in children. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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