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Article ; Online: TMA in Kidney Transplantation.

Imanifard, Zahra / Liguori, Lucia / Remuzzi, Giuseppe

2023 Volume 107, Issue 11, Page(s) 2329–2340

Abstract: Thrombotic microangiopathy (TMA) is a rare and devastating complication of kidney transplantation, which often leads to graft failure. Posttransplant TMA (PT-TMA) may occur either de novo or as a recurrence of the disease. De novo TMA can be triggered by ...

Abstract	Thrombotic microangiopathy (TMA) is a rare and devastating complication of kidney transplantation, which often leads to graft failure. Posttransplant TMA (PT-TMA) may occur either de novo or as a recurrence of the disease. De novo TMA can be triggered by immunosuppressant drugs, antibody-mediated rejection, viral infections, and ischemia/reperfusion injury in patients with no evidence of the disease before transplantation. Recurrent TMA may occur in the kidney grafts of patients with a history of atypical hemolytic uremic syndrome (aHUS) in the native kidneys. Studies have shown that some patients with aHUS carry genetic abnormalities that affect genes that code for complement regulators (CFH, MCP, CFI) and components (C3 and CFB), whereas in 10% of patients (mostly children), anti-FH autoantibodies have been reported. The incidence of aHUS recurrence is determined by the underlying genetic or acquired complement abnormality. Although treatment of the causative agents is usually the first line of treatment for de novo PT-TMA, this approach might be insufficient. Plasma exchange typically resolves hematologic abnormalities but does not improve kidney function. Targeted complement inhibition is an effective treatment for recurrent TMA and may be effective in de novo PT-TMA as well, but it is necessary to establish which patients can benefit from different therapeutic options and when and how these can be applied.
Language	English
Publishing date	2023-10-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004585
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Article: Case Report: Tackling Complement Hyperactivation With Eculizumab in Atypical Hemolytic Uremic Syndrome Triggered by COVID-19.

Leone, Valentina Fanny / Imeraj, Amantia / Gastoldi, Sara / Mele, Caterina / Liguori, Lucia / Condemi, Carmelita / Ruggenenti, Piero / Remuzzi, Giuseppe / Carrara, Camillo

Frontiers in pharmacology

2022 Volume 13, Page(s) 842473

Abstract: Hemolytic uremic syndrome (HUS) is a rare life-threatening disease of unrestrained complement system dysregulation, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure in genetically predisposed individuals. In this report, we ... ...

Abstract	Hemolytic uremic syndrome (HUS) is a rare life-threatening disease of unrestrained complement system dysregulation, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure in genetically predisposed individuals. In this report, we describe two cases of SARS-CoV-2-associated HUS treated with eculizumab, a C5-blocking monoclonal antibody reported to be remarkably effective in the treatment of HUS. Detailed biochemical and genetic complement system analysis is reported, and the prompt clinical response after C5 pharmacological blockade is documented. Our report provides the rationale and supports the use of terminal complement pathway inhibition for the treatment of SARS-CoV-2-associated HUS.
Language	English
Publishing date	2022-02-28
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.842473
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Article ; Online: Mycoplasma pneumoniae Infection Associated with Anti-Factor H Autoantibodies in Atypical Hemolytic Uremic Syndrome.

Valoti, Elisabetta / Piras, Rossella / Mele, Caterina / Alberti, Marta / Liguori, Lucia / Breno, Matteo / Bertulli, Cristina / Bresin, Elena / Donadelli, Roberta

Nephron

2022 Volume 146, Issue 6, Page(s) 593–598

Abstract: Hemolytic uremic syndrome (HUS) is a rare disease characterized by hemolytic anemia, thrombocytopenia, and renal impairment mostly triggered by strains of Shiga-like toxin-producing Escherichia coli (STEC-HUS). A rarer form of HUS, defined as atypical ... ...

Abstract	Hemolytic uremic syndrome (HUS) is a rare disease characterized by hemolytic anemia, thrombocytopenia, and renal impairment mostly triggered by strains of Shiga-like toxin-producing Escherichia coli (STEC-HUS). A rarer form of HUS, defined as atypical HUS (aHUS), is associated with genetic or acquired dysregulation of the alternative pathway of the complement system and presents a poorer prognosis than STEC-HUS. Factor H autoantibodies (anti-FHs) have been reported in aHUS in 5-11% of cases and are strongly associated with the homozygous deletion of CFHR3-CFHR1 genes. In the large majority of patients, anti-FH-associated aHUS is commonly preceded by gastrointestinal or respiratory tract infections. Here, we described the clinical case of a 3-year-old boy who was hospitalized for aHUS preceded by Mycoplasma pneumoniae (MP) infection. He resulted positive for anti-FHs and carried the homozygous deletion of CFHR3-CFHR1. Of relevance, he also showed a variant of unknown significance in the C5 gene. The patient was successfully treated with eculizumab and achieved hematological and renal remission. The anti-FH titer decreased, became negative after 6 months of mycophenolate mofetil (MMF) treatment, and remained negative for 21-month follow-up indicating that immunosuppression was effective and could prevent the reappearance of anti-FHs. We hypothesized that MP, likely through an evasion strategy of immunosurveillance based on binding of pathogen to FH, triggers anti-FH antibody generation and aHUS in a subject genetically predisposed. In conclusion, to the best of our knowledge, here, we reported the first case of anti-FH-mediated aHUS after an MP infection who benefited from eculizumab and immunosuppressive therapy based on MMF. Hence, monitoring of anti-FHs in patients with post-MP infection glomerulonephritis could be recommended, especially in those with low C3 plasma levels.
MeSH term(s)	Humans ; Child, Preschool ; Atypical Hemolytic Uremic Syndrome ; Autoantibodies ; Pneumonia, Mycoplasma ; Homozygote ; Sequence Deletion
Chemical Substances	Autoantibodies
Language	English
Publishing date	2022-04-11
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000523998
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Article ; Online: CFH

Piras, Rossella / Valoti, Elisabetta / Alberti, Marta / Bresin, Elena / Mele, Caterina / Breno, Matteo / Liguori, Lucia / Donadelli, Roberta / Rigoldi, Miriam / Benigni, Ariela / Remuzzi, Giuseppe / Noris, Marina

Frontiers in immunology

2023 Volume 13, Page(s) 1011580

Abstract: Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disease that manifests with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, and is associated with dysregulation of the alternative complement pathway. The ... ...

Abstract	Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disease that manifests with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, and is associated with dysregulation of the alternative complement pathway. The chromosomal region including Methods: In this study, we report the results of Results: We found uncommon SVs in 8% of patients with primary aHUS: 70% carried rearrangements involving Discussion: In conclusion, these data highlight that uncommon
MeSH term(s)	Humans ; Atypical Hemolytic Uremic Syndrome/epidemiology ; Atypical Hemolytic Uremic Syndrome/genetics ; Atypical Hemolytic Uremic Syndrome/drug therapy ; Complement Factor H/genetics ; Prevalence ; DNA Copy Number Variations ; Neoplasm Recurrence, Local ; Genomics
Chemical Substances	Complement Factor H (80295-65-4)
Language	English
Publishing date	2023-01-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1011580
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Article ; Online: An

Gastoldi, Sara / Aiello, Sistiana / Galbusera, Miriam / Breno, Matteo / Alberti, Marta / Bresin, Elena / Mele, Caterina / Piras, Rossella / Liguori, Lucia / Santarsiero, Donata / Benigni, Ariela / Remuzzi, Giuseppe / Noris, Marina

Frontiers in immunology

2023 Volume 14, Page(s) 1112257

Abstract: Introduction: Comprehensive genetic analysis is essential to clinical care of patients with atypical haemolytic uremic syndrome (aHUS) to reinforce diagnosis, and to guide treatment. However, the characterization of complement gene variants remains ... ...

Abstract	Introduction: Comprehensive genetic analysis is essential to clinical care of patients with atypical haemolytic uremic syndrome (aHUS) to reinforce diagnosis, and to guide treatment. However, the characterization of complement gene variants remains challenging owing to the complexity of functional studies with mutant proteins. This study was designed: 1) To identify a tool for rapid functional determination of complement gene variants; 2) To uncover inherited complement dysregulation in aHUS patients who do not carry identified gene variants. Methods: To address the above goals, we employed an ex-vivo assay of serum-induced C5b-9 formation on ADP-activated endothelial cells in 223 subjects from 60 aHUS pedigrees (66 patients and 157 unaffected relatives). Results: Sera taken from all aHUS patients in remission induced more C5b-9 deposition than control sera, independently from the presence of complement gene abnormalities. To avoid the possible confounding effects of chronic complement dysregulation related to aHUS status, and considering the incomplete penetrance for all aHUS-associated genes, we used serum from unaffected relatives. In control studies, 92.7% of unaffected relatives with known pathogenic variants exhibited positive serum-induced C5b-9 formation test, documenting a high sensitivity of the assay to identify functional variants. The test was also specific, indeed it was negative in all non-carrier relatives and in relatives with variants non-segregating with aHUS. All but one variants in aHUS-associated genes predicted in-silico as likely pathogenic or of uncertain significance (VUS) or likely benign resulted as pathogenic in the C5b-9 assay. At variance, variants in putative candidate genes did not exhibit a functional effect, with the exception of a Discussion: In conclusion, the serum-induced C5b-9 formation test in unaffected relatives of aHUS patients may be a tool for rapid functional evaluation of rare complement gene variants. When combined with exome sequencing the assay might be of help in variant selection, to identify new aHUS-associated genetic factors.
MeSH term(s)	Humans ; Complement Membrane Attack Complex/genetics ; Complement Membrane Attack Complex/metabolism ; Endothelial Cells/metabolism ; Atypical Hemolytic Uremic Syndrome/diagnosis ; Atypical Hemolytic Uremic Syndrome/genetics ; Complement System Proteins/genetics ; Complement System Proteins/therapeutic use ; Pedigree
Chemical Substances	Complement Membrane Attack Complex ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2023-02-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1112257
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Article ; Online: Extraction, isolation, and purification of analytes from samples of marine origin--a multivariate task.

Liguori, Lucia / Bjørsvik, Hans-René

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2012 Volume 910, Page(s) 46–53

Abstract: The development of a multivariate study for a quantitative analysis of six different polybrominated diphenyl ethers (PBDEs) in tissue of Atlantic Salmo salar L. is reported. An extraction, isolation, and purification process based on an accelerated ... ...

Abstract	The development of a multivariate study for a quantitative analysis of six different polybrominated diphenyl ethers (PBDEs) in tissue of Atlantic Salmo salar L. is reported. An extraction, isolation, and purification process based on an accelerated solvent extraction system was designed, investigated, and optimized by means of statistical experimental design and multivariate data analysis and regression. An accompanying gas chromatography-mass spectrometry analytical method was developed for the identification and quantification of the analytes, BDE 28, BDE 47, BDE 99, BDE 100, BDE 153, and BDE 154. These PBDEs have been used in commercial blends that were used as flame-retardants for a variety of materials, including electronic devices, synthetic polymers and textiles. The present study revealed that an extracting solvent mixture composed of hexane and CH₂Cl₂ (10:90) provided excellent recoveries of all of the six PBDEs studied herein. A somewhat lower polarity in the extracting solvent, hexane and CH₂Cl₂ (40:60) decreased the analyte %-recoveries, which still remain acceptable and satisfactory. The study demonstrates the necessity to perform an intimately investigation of the extraction and purification process in order to achieve quantitative isolation of the analytes from the specific matrix.
MeSH term(s)	Animals ; Flame Retardants/analysis ; Food Contamination/analysis ; Gas Chromatography-Mass Spectrometry/methods ; Halogenated Diphenyl Ethers/analysis ; Halogenated Diphenyl Ethers/isolation & purification ; Salmo salar ; Seafood/analysis ; Seawater/analysis ; Solid Phase Extraction/methods ; Water Pollutants, Chemical/analysis
Chemical Substances	Flame Retardants ; Halogenated Diphenyl Ethers ; Water Pollutants, Chemical
Language	English
Publishing date	2012-12-01
Publishing country	Netherlands
Document type	Evaluation Studies ; Journal Article
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2012.06.038
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Article ; Online: A GWAS in the pandemic epicenter highlights the severe COVID-19 risk locus introgressed by Neanderthals.

iScience

2023 Volume 26, Issue 10, Page(s) 107629

Abstract: Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of COVID-19 ...

Abstract	Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of COVID-19 outcome in a homogeneous population who experienced a high exposure to the virus and with a known infection status. We recruited inhabitants of Bergamo province-that in spring 2020 was the epicenter of the SARS-Cov-2 pandemic in Europe-via an online questionnaire followed by personal interviews. Cases and controls were matched by age, sex and risk factors. We genotyped 1195 individuals and replicated the association at the 3p21.31 locus with severity, but with a stronger effect size that further increased in gravely ill patients. Transcriptome-wide association study highlighted eQTLs for
Language	English
Publishing date	2023-08-16
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107629
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Article ; Online: C5a and C5aR1 are key drivers of microvascular platelet aggregation in clinical entities spanning from aHUS to COVID-19.

Aiello, Sistiana / Gastoldi, Sara / Galbusera, Miriam / Ruggenenti, Piero / Portalupi, Valentina / Rota, Stefano / Rubis, Nadia / Liguori, Lucia / Conti, Sara / Tironi, Matteo / Gamba, Sara / Santarsiero, Donata / Benigni, Ariela / Remuzzi, Giuseppe / Noris, Marina

Blood advances

2021 Volume 6, Issue 3, Page(s) 866–881

Abstract: Unrestrained activation of the complement system till the terminal products, C5a and C5b-9, plays a pathogenetic role in acute and chronic inflammatory diseases. In endothelial cells, complement hyperactivation may translate into cell dysfunction, ... ...

Abstract	Unrestrained activation of the complement system till the terminal products, C5a and C5b-9, plays a pathogenetic role in acute and chronic inflammatory diseases. In endothelial cells, complement hyperactivation may translate into cell dysfunction, favoring thrombus formation. The aim of this study was to investigate the role of the C5a/C5aR1 axis as opposed to C5b-9 in inducing endothelial dysfunction and loss of antithrombogenic properties. In vitro and ex vivo assays with serum from patients with atypical hemolytic uremic syndrome (aHUS), a prototype rare disease of complement-mediated microvascular thrombosis due to genetically determined alternative pathway dysregulation, and cultured microvascular endothelial cells, demonstrated that the C5a/C5aR1 axis is a key player in endothelial thromboresistance loss. C5a added to normal human serum fully recapitulated the prothrombotic effects of aHUS serum. Mechanistic studies showed that C5a caused RalA-mediated exocytosis of von Willebrand factor (vWF) and P-selectin from Weibel-Palade bodies, which favored further vWF binding on the endothelium and platelet adhesion and aggregation. In patients with severe COVID-19 who suffered from acute activation of complement triggered by severe acute respiratory syndrome coronavirus 2 infection, we found the same C5a-dependent pathogenic mechanisms. These results highlight C5a/C5aR1 as a common prothrombogenic effector spanning from genetic rare diseases to viral infections, and it may have clinical implications. Selective C5a/C5aR1 blockade could have advantages over C5 inhibition because the former preserves the formation of C5b-9, which is critical for controlling bacterial infections that often develop as comorbidities in severely ill patients. The ACCESS trial registered at www.clinicaltrials.gov as #NCT02464891 accounts for the results related to aHUS patients treated with CCX168.
MeSH term(s)	Atypical Hemolytic Uremic Syndrome ; COVID-19 ; Endothelial Cells ; Humans ; Platelet Aggregation ; SARS-CoV-2
Language	English
Publishing date	2021-11-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021005246
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Zs.A 7153: Show issues

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Article ; Online: Organocatalyzed epoxidation of alkenes in continuous flow using a multi-jet oscillating disk reactor.

Spaccini, Raffaele / Liguori, Lucia / Punta, Carlo / Bjørsvik, Hans-René

ChemSusChem

2012 Volume 5, Issue 2, Page(s) 261–265

MeSH term(s)	Alkenes/chemistry ; Catalysis ; Epoxy Compounds/chemistry ; Microtechnology/instrumentation
Chemical Substances	Alkenes ; Epoxy Compounds
Language	English
Publishing date	2012-02-13
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1864-564X
ISSN (online)	1864-564X
DOI	10.1002/cssc.201100262
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Article ; Online: Impact of SARS-CoV-2 Omicron and Delta variants in patients requiring intensive care unit (ICU) admission for COVID-19, Northern Italy, December 2021 to January 2022.

Piralla, Antonio / Mojoli, Francesco / Pellegrinelli, Laura / Ceriotti, Ferruccio / Valzano, Antonia / Grasselli, Giacomo / Gismondo, Maria Rita / Micheli, Valeria / Castelli, Antonio / Farina, Claudio / Arosio, Marco / Lorini, Ferdinando Luca / Fanti, Diana / Busni, Andrea / Laratta, Matteo / Maggi, Fabrizio / Novazzi, Federica / Cabrini, Luca / Callegaro, Anna Paola /

Keim, Roberto / Remuzzi, Giuseppe / Cavallero, Annalisa / Malandrin, Sergio Maria Ivano / Rona, Roberto / Giardina, Federica / Ferrari, Guglielmo / Zavaglio, Federica / D'angelo, Piera / Galli, Cristina / Bubba, Laura / Binda, Sandro / Oggioni, Massimo / Uceda Renteria, Sara Colonia / Bono, Patrizia / Baj, Andreina / Ferrante, Francesca Drago / Guarneri, Davide / Tonelli, Marco / Napolitano, Gavino / Nava, Alice / Romeo, Lorenzo / Nicolini, Elena / Valaperta, Rea / Varisano, Ludovica / Mele, Caterina / Liguori, Lucia / Raggi, Monica / Mongodi, Silvia / Pagani, Michele / Severgnini, Paolo / Gasberti, Dario / Bonanomi, Ezio / Gritti, Paolo / Marrazzo, Francesco / Giovannini, Ilaria / Sacchi, Noemi / Sagliocco, Orlando / Cereda, Danilo / Buoro, Sabrina / Baldanti, Fausto / Pariani, Elena

Respiratory medicine and research

2023 Volume 83, Page(s) 100990

Abstract: This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of ... ...

Abstract	This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic.
MeSH term(s)	Adult ; Humans ; SARS-CoV-2 ; COVID-19/epidemiology ; Inpatients ; Intensive Care Units ; Italy/epidemiology
Language	English
Publishing date	2023-03-04
Publishing country	France
Document type	Multicenter Study ; Observational Study ; Journal Article
ISSN	2590-0412
ISSN (online)	2590-0412
DOI	10.1016/j.resmer.2023.100990
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