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Search results for: APOL1

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#34559857   2021/09/24 To Up

Interplay of Trypanosome Lytic Factor and innate immune cells in the resolution of cutaneous Leishmania infection.

Trypanosome Lytic Factor (TLF) is a primate-specific high-density lipoprotein (HDL) complex that, through the cation channel-forming protein apolipoprotein L-1 (APOL1), provides innate immunity to a select kinetoplastid parasites. The immunoprotective effects of TLF have been extensively investigated in the context of its interaction with the extracellular protozoan Trypanosoma brucei brucei, to which it confers sterile immunity. We previously showed that TLF could act against intracellular pathogen Leishmania, and here we dissected the role of TLF and its synergy with host-immune cells. Leishmania major is transmitted by Phlebotomine sand flies, which deposit the parasite intradermally into mammalian hosts, where neutrophils are the predominant phagocytes recruited to the site of infection. Once in the host, the parasites are phagocytosed and shed their surface glycoconjugates during differentiation to the mammalian-resident amastigote stage. Our data show that mice producing TLF have reduced parasite burdens when infected intradermally with metacyclic promastigotes of L. major, the infective, fly-transmitted stage. This TLF-mediated reduction in parasite burden was lost in neutrophil-depleted mice, suggesting that early recruitment of neutrophils is required for TLF-mediated killing of L. major. In vitro we find that only metacyclic promastigotes co-incubated with TLF in an acidic milieu were lysed. However, amastigotes were not killed by TLF at any pH. These findings correlated with binding experiments, revealing that labeled TLF binds specifically to the surface of metacyclic promastigotes, but not to amastigotes. Metacyclic promastigotes of L. major deficient in the synthesis of surface glycoconjugates LPG and/or PPG (lpg1- and lpg5A-/lpg5B- respectively whose absence mimics the amastigote surface, were resistant to TLF-mediated lysis. We propose that TLF binds to the outer surface glycoconjugates of metacyclic promastigotes, whereupon it kills the parasite in acidic phagosome of phagocytes. We hypothesize that resistance to TLF requires shedding of the surface glycoconjugates, which occurs several hours after phagocytosis by immune cells, creating a relatively short-lived but effective window for TLF to act against Leishmania.
Jyoti Pant, Marie Samanovic, Maria T Nelson, Mert K Keceli, Joseph Verdi, Stephen M Beverley, Jayne Raper

1562 related Products with: Interplay of Trypanosome Lytic Factor and innate immune cells in the resolution of cutaneous Leishmania infection.

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#34559399   2021/09/24 To Up

Collapsing glomerulopathy in a patient with APOL1 intermediate-risk genotype triggered by lupus nephritis and SARS-CoV-2 infection: lessons for the clinical nephrologist.


Christophe Masset, Karine Renaudin, Delphine Kervella, Agnès Chapelet, Clément Deltombe, Simon Ville

2726 related Products with: Collapsing glomerulopathy in a patient with APOL1 intermediate-risk genotype triggered by lupus nephritis and SARS-CoV-2 infection: lessons for the clinical nephrologist.



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#34546508   2021/09/21 To Up

Mutational landscape of TRPC6, WT1, LMX1B, APOL1, PTPRO, PMM2, LAMB2 and WT1 genes associated with Steroid resistant nephrotic syndrome.

Nephrotic syndrome appears as a group of symptoms like proteinuria, edema and hyperlipidemia. Identification of monogenic forms revealed the physiology and pathogenesis of the SRNS.
Jinal M Thakor, Glory Parmar, Kinnari N Mistry, Sishir Gang, Dharamshibhai N Rank, Chaitanya G Joshi

2768 related Products with: Mutational landscape of TRPC6, WT1, LMX1B, APOL1, PTPRO, PMM2, LAMB2 and WT1 genes associated with Steroid resistant nephrotic syndrome.

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#34545573   2021/09/20 To Up

Clinical and genetic factors are associated with kidney complications in African children with sickle cell anaemia.

Clinical and genetic factors have been reported as influencing the development of sickle cell nephropathy (SCN). However, such data remain limited in the paediatric population. In this cross-sectional study, we enrolled 361 sickle cell disease children from the Democratic Republic of Congo. Participants were genotyped for the beta (β)-globin gene, apolipoprotein L1 (APOL1) risk variants, and haem oxygenase-1 (HMOX1) GT-dinucleotide repeats. As markers of kidney damage, albuminuria, hyperfiltration and decreased estimated glomerular filtration with creatinine (eGFRcr) were measured. An association of independent clinical and genetic factors with these markers of kidney damage were assessed via regression analysis. Genetic sequencing confirmed sickle cell anaemia in 326 participants. Albuminuria, hyperfiltration and decreased eGFRcr were present in 65 (20%), 52 (16%) and 18 (5·5%) patients, respectively. Regression analysis revealed frequent blood transfusions, indirect bilirubin and male gender as clinical predictors of SCN. APOL1 high-risk genotype (G1/G1, G2/G2 and G1/G2) was significantly associated with albuminuria (P = 0·04) and hyperfiltration (P = 0·001). HMOX1 GT-dinucleotide long repeats were significantly associated with lower eGFRcr. The study revealed a high burden of kidney damage among Congolese children and provided evidence of the possible role of APOL1 and HMOX1 in making children more susceptible to kidney complications.
Oyindamola Christiana Adebayo, DieuMerci Kabasele Betukumesu, Agathe Bikupe Nkoy, Oluyomi Modupe Adesoji, Pepe Mfutu Ekulu, Lambertus P Van den Heuvel, Elena N Levtchenko, Veerle Labarque

2362 related Products with: Clinical and genetic factors are associated with kidney complications in African children with sickle cell anaemia.

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#34514214   2021/06/19 To Up

Collapsing Glomerulopathy in Identical Twins With Lupus and High-Risk Apolipoprotein L1 () Genotype.


Margaret DeOliveira, Colby Feeney, Caroline Leahy, Sarah Nystrom, David N Howell, Samira S Farouk, Ming Wu, Opeyemi A Olabisi, Matthew A Sparks

2252 related Products with: Collapsing Glomerulopathy in Identical Twins With Lupus and High-Risk Apolipoprotein L1 () Genotype.

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#34513880   2021/08/27 To Up

HIV Viremia Is Associated With Variants and Reduced JC-Viruria.

Variants in the () gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two risk alleles, a role in HIV infectivity has been postulated in the mechanism of associated kidney disease. Herein, we aim to explore the association between HIV viremia and genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.
Etty Kruzel-Davila, Barbara Mensah Sankofi, Ernestine Kubi Amos-Abanyie, Anita Ghansah, Alexander Nyarko, Seth Agyemang, Gordon A Awandare, Moran Szwarcwort-Cohen, Anat Reiner-Benaim, Basem Hijazi, Ifeoma Ulasi, Yemi Raheem Raji, Vincent Boima, Charlotte Osafo, Victoria May Adabayeri, Michael Matekole, Timothy O Olanrewaju, Samuel Ajayi, Manmak Mamven, Sampson Antwi, Adebowale D Ademola, Jacob Plange-Rhule, Fatiu Arogundade, Priscilla Abena Akyaw, Cheryl A Winkler, Babatunde L Salako, Akinlolu Ojo, Karl Skorecki, Dwomoa Adu

2464 related Products with: HIV Viremia Is Associated With Variants and Reduced JC-Viruria.

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#34499625   2021/09/09 To Up

Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes.

Apolipoprotein L1 (APOL1) risk-alleles in donor kidneys associate with graft loss but whether recipient risk-allele expression impacts transplant outcomes is unclear. To test whether recipient APOL1 risk-alleles independently correlate with transplant outcomes, we analyzed genome-wide SNP genotyping data of donors and recipients from two kidney transplant cohorts, Genomics of Chronic Allograft Rejection (GOCAR) and Clinical Trials in Organ Transplantation (CTOT1/17). We estimated genetic ancestry (quantified as proportion of African ancestry or pAFR) by ADMIXTURE and correlated APOL1 genotypes and pAFR with outcomes. In the GOCAR discovery set, we observed that the number of recipient APOL1 G1/G2 alleles (R-nAPOL1) associated with increased risk of death-censored allograft loss (DCAL), independent of ancestry (HR = 2.14; P = 0.006), and within the subgroup of African American and Hispanic (AA/H) recipients (HR = 2.36; P = 0.003). R-nAPOL1 also associated with increased risk of any T cell-mediated rejection (TCMR) event. These associations were validated in CTOT1/17. Ex vivo studies of peripheral blood mononuclear cells revealed unanticipated high APOL1 expression in activated CD4+/CD8+ T cells and natural killer cells. We detected enriched immune response gene pathways in risk-allele carriers vs. non-carriers on the kidney transplant waitlist and among healthy controls. Our findings demonstrate an immunomodulatory role for recipient APOL1 risk-alleles associating with TCMR and DCAL. This finding has broader implications for immune mediated injury to native kidneys.
Zhongyang Zhang, Zeguo Sun, Jia Fu, Qisheng Lin, Khadija Banu, Kinsuk Chauhan, Marina Planoutene, Chengguo Wei, Fadi Salem, Zhengzi Yi, Ruijie Liu, Paolo Cravedi, Haoxiang Cheng, Ke Hao, Philip J O'Connell, Shuta Ishibe, Weijia Zhang, Steven G Coca, Ian W Gibson, Robert B Colvin, John C He, Peter S Heeger, Barbara T Murphy, Madhav C Menon

2944 related Products with: Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes.

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#34449991   // To Up

Relative Contribution of Genetic and Environmental Factors in CKD.

Chronic kidney disease affects nearly 15 percent of the U.S. population. Onset and rate of progression are influenced by a combination of genetic and non-genetic factors. Because health care systems across the U.S. are beginning to deploy automated decision support to stratify patients at risk, we review the relative impact of genetic factors (e.g., APOL1 gene polymorphisms) and non-genetic factors (e.g., clinical comorbidities and exposure to environmental nephrotoxins) contributing to this common disease. Overall, the impact of non-genetic factors appears to exceed the impact of genetic factors.
Derek E Lee, Mohammad Qamar, Russell A Wilke

1123 related Products with: Relative Contribution of Genetic and Environmental Factors in CKD.

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#34440683   2021/07/28 To Up

Novel Human Podocyte Cell Model Carrying G2/G2 APOL1 High-Risk Genotype.

Apolipoprotein L1 () high-risk genotypes (HRG), G1 and G2, increase the risk of various non-diabetic kidney diseases in the African population. To date, the precise mechanisms by which risk variants induce injury on podocytes and other kidney cells remain unclear. Trying to unravel these mechanisms, most studies have used animal or cell models created by gene editing. We developed and characterised conditionally immortalised human podocyte cell lines derived from urine of a donor carrying HRG G2/G2. Following induction of APOL1 expression by polyinosinic-polycytidylic acid (poly(I:C)), we assessed functional features of APOL1-induced podocyte dysfunction. As control, APOL1 wild type (G0/G0) podocyte cell line previously generated from a Caucasian donor was used. Upon exposure to poly(I:C), G2/G2 and G0/G0 podocytes upregulated APOL1 expression resulting in podocytes detachment, decreased cells viability and increased apoptosis rate in a genotype-independent manner. Nevertheless, G2/G2 podocyte cell lines exhibited altered features, including upregulation of CD2AP, alteration of cytoskeleton, reduction of autophagic flux and increased permeability in an in vitro model under continuous perfusion. The human APOL1 G2/G2 podocyte cell model is a useful tool for unravelling the mechanisms of APOL1-induced podocyte injury and the cellular functions of APOL1.
Pepe M Ekulu, Oyindamola C Adebayo, Jean-Paul Decuypere, Linda Bellucci, Mohamed A Elmonem, Agathe B Nkoy, Djalila Mekahli, Benedetta Bussolati, Lambertus P van den Heuvel, Fanny O Arcolino, Elena N Levtchenko

2167 related Products with: Novel Human Podocyte Cell Model Carrying G2/G2 APOL1 High-Risk Genotype.

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#34366528   2021/08/03 To Up

[Ig a vasculitis with nephritis (henoch-schönlein purpura) after covid-19: a case series and review of the literature.]

COVID-19 most related glomerular disease to date seems to be collapsing glomerulopathy, mostly in young Afroamerican patients with APOL1 gene risk alleles. However, in our population, predominant in elderly Caucasian patients, most biopsied pathology since the beginning of the pandemic has been IgA nephritis or Schönlein-Henoch purpura.Since the description of the first case of this entity after SARS-CoV-2 infection by our research group, three more cases have arisen, which are described in the following article. In contrast to the rest of IgA vasculitis cases reported, our patients presented more renal function deterioration and all of them required immunosupresive therapy. Moreover, some showed incomplete recovery of renal function.This case series strengthens the hypothesis that SARS-CoV-2 infection may be another trigger of this pathology.
Irene Oñate, Milagros Ortiz, Andrea Suso, Carmen Mon, Karen Galindo, Carolina Lentisco, Rosa Camacho, María Sánchez, Aniana Oliet, Olimpia Ortega, Juan C Herrero, José A Cortés, Alejandro Pascual

1683 related Products with: [Ig a vasculitis with nephritis (henoch-schönlein purpura) after covid-19: a case series and review of the literature.]

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