Atypical hemolytic uremic syndrome induced by SARS-CoV2 infection in infants with EXOSC3 mutation

Quekelberghe, Chantal Van; Latta, Kay; Kunzmann, Steffen; Grohmann, Maik; Hansen, Matthias

doi:10.1007/s00467-022-05566-6

Cited by 8 publications

(4 citation statements)

References 12 publications

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“…To establish a comprehensive immune cell–complement pathway interaction network, we used the STRING database, integrating identified pathway interactions with aHUS-associated genes, including CFH , CD46 , CFI , C3 , CFB , THBD , CFHR1-5 , DGKE , VTR , C2 , C3AR1 , C8B , C9 , C4BPA , CFD , MASP1-2 , MMACHC , PLG , WT1 , VWF , CR1 , CXCL12 , C5 , TLR4 , CXCR4 , HASP , KNK , INF2 , EXOSC3 , TSEN2 , CD36 , and VTN [ 2 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. The enriched pathways in aHUS patients include ALCAM-CD6, IL16-CD4, APP-CD40, CD86-CTLA4, CXC, and SELPLG ( Figure 11 a–d and Figure S12a,b ).…”

Section: Resultsmentioning

confidence: 99%

Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome

Chen

Huang

et al. 2023

IJMS

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Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy. Definitive biomarkers for disease diagnosis and activity remain elusive, making the exploration of molecular markers paramount. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 unaffected family members of aHUS patients, and 4 healthy controls. We identified 32 distinct subpopulations encompassing 5 B-cell types, 16 T- and natural killer (NK) cell types, 7 monocyte types, and 4 other cell types. Notably, we observed a significant increase in intermediate monocytes in unstable aHUS patients. Subclustering analysis revealed seven elevated expression genes, including NEAT1, MT-ATP6, MT-CYB, VIM, ACTG1, RPL13, and KLRB1, in unstable aHUS patients, and four heightened expression genes, including RPS27, RPS4X, RPL23, and GZMH genes, in stable aHUS patients. Additionally, an increase in the expression of mitochondria-related genes suggested a potential influence of cell metabolism on the clinical progression of the disease. Pseudotime trajectory analysis revealed a unique immune cell differentiation pattern, while cell—cell interaction profiling highlighted distinctive signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

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Section: Resultsmentioning

confidence: 99%

Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome

Chen

Huang

et al. 2023

IJMS

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“…Over the course of the pandemic, novel conditions and complications have surfaced, such as multisystem inflammatory syndrome in children (MIS-C), which frequently resembles other established diseases, such as thrombotic microangiopathy or Kawasaki disease [ 39 , 40 ]. Infection with this virus can lead to a wide range of clinical manifestations, including pediatric TMA, as shown by a growing number of clinical case reports [ 16 , 18 , 19 , 41 , 42 ]. Although still unclear, the mechanisms behind this association might be related to loss of protection of endothelial cells and thrombocytes against complement membrane attack complexes.…”

Section: Discussionmentioning

confidence: 99%

Pitfalls of Thrombotic Microangiopathies in Children: Two Case Reports and Literature Review

et al. 2023

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Thrombotic microangiopathy can present itself in the form of several clinical entities, representing a real challenge for diagnosis and treatment in pediatric practice. Our article aims to explore the evolution of two rare cases of pediatric thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) with extremely similar clinical pictures, which, coincidentally, presented at approximately the same time in our hospital. These cases and our literature review demonstrate the multiple facets of thrombotic microangiopathy, which can produce various determinations and salient manifestations even among the pediatric population. TTP and aHUS may represent genuine diagnostic pitfalls through the overlap of their clinical and biological findings, although they develop through fundamentally different mechanisms that require different therapeutic approaches. As a novelty, we underline that COVID-19 infection cannot be excluded as potential trigger for TTP and aHUS in our patients and we predict that other reports of such an association will follow, raising a complex question of COVID-19’s implication in the occurrence and evolution of thrombotic microangiopathies. On this matter, we conducted literature research that resulted in 15 cases of COVID-19 pediatric infections associated with either TTP or aHUS. Taking into consideration the morbidity associated with TTP and aHUS, an elaborate differential diagnosis and prompt intervention are of the essence.

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“…7 Pediatric reports are much scarcer. One 3-year-old Turkish child with consanguineous parents and a history of 2 siblings succumbing to unknown cause at the ages of 7 months and 1.5 years, 8 and two Roman Bulgarian infants with mutations in the EXOSC3 gene, which encodes a multiprotein ribonuclease complex crucial for RNA processing 9 were reported. One 14-year-old adolescent girl was reported to have TMA triggered by COVID-19, which required intubation.…”

Section: Discussionmentioning

confidence: 99%

A Renal Disease Triggered by COVID-19

Gençay,

Işık,

Yürük Yıldırım

et al. 2023

Clin Pediatr (Phila)

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Atypical hemolytic uremic syndrome induced by SARS-CoV2 infection in infants with EXOSC3 mutation

Cited by 8 publications

References 12 publications

Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome

Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome

Pitfalls of Thrombotic Microangiopathies in Children: Two Case Reports and Literature Review

A Renal Disease Triggered by COVID-19

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