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Article ; Online: Controling the cytoskeleton during CEACAM3-mediated phagocytosis.

Kuiper, Johannes W P / Gregg, Helena L / Schüber, Meike / Klein, Jule / Hauck, Christof R

2024 Volume 103, Issue 1, Page(s) 151384

Abstract: Phagocytosis, an innate defense mechanism of multicellular animals, is initiated by specialized surface receptors. A phagocytic receptor expressed by human polymorphonuclear granulocytes, the major professional phagocytes in our body, is one of the ... ...

Abstract	Phagocytosis, an innate defense mechanism of multicellular animals, is initiated by specialized surface receptors. A phagocytic receptor expressed by human polymorphonuclear granulocytes, the major professional phagocytes in our body, is one of the fastest evolving human proteins implying a special role in human biology. This receptor, CEACAM3, is a member of the CarcinoEmbryonic Antigen-related Cell Adhesion Molecule (CEACAM) family and dedicated to the immediate recognition and rapid internalization of human-restricted pathogens. In this focused contribution, we will review the special adaptations of this protein, which co-evolves with different species of mucosa-colonizing bacteria. While the extracellular Immunoglobulin-variable (Ig
MeSH term(s)	Animals ; Humans ; Phagocytosis ; Cell Adhesion Molecules ; Cytoskeleton ; Signal Transduction ; Phosphorylation ; Carcinoembryonic Antigen
Chemical Substances	Cell Adhesion Molecules ; CEACAM3 protein, human ; Carcinoembryonic Antigen
Language	English
Publishing date	2024-01-05
Publishing country	Germany
Document type	Review ; Journal Article
ZDB-ID	391967-5
ISSN	1618-1298 ; 0070-2463 ; 0171-9335
ISSN (online)	1618-1298
ISSN	0070-2463 ; 0171-9335
DOI	10.1016/j.ejcb.2024.151384
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Article ; Online: A genome-wide genetic screen identifies CYRI-B as a negative regulator of CEACAM3-mediated phagocytosis.

Kuiper, Johannes W P / Krause, Julia / Potgeter, Leon / Adrian, Jonas / Hauck, Christof R

Journal of cell science

2023 Volume 136, Issue 11

Abstract: Opsonin-independent phagocytosis mediated by human carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) has evolved to control a subset of human-restricted bacterial pathogens. CEACAM3 engagement triggers rapid GTP-loading of the small ... ...

Abstract	Opsonin-independent phagocytosis mediated by human carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) has evolved to control a subset of human-restricted bacterial pathogens. CEACAM3 engagement triggers rapid GTP-loading of the small GTPase Rac as a master regulator of cytoskeletal rearrangements and lamellipodia-driven internalization. To identify components of the CEACAM3-initiated signaling cascade, we performed a genome-wide CRISPR/Cas9-based screen in human myeloid cells. Following infection with fluorescently labeled bacteria, cells exhibiting elevated phagocytosis (gain-of-function) as well as cells showing reduced phagocytosis (loss-of-function) were sorted and enrichment of individual single-guide RNAs (sgRNAs) was determined by next generation sequencing. Concentrating on genes whose targeting by three distinct sgRNAs consistently resulted in a gain-of-function phenotype, we identified the Rac-GTP-sequestering protein CYRI-B as a negative regulator of CEACAM3-mediated phagocytosis. Clonal HL-60 cell lines with CYRI-B knockout showed enhanced CEACAM3-downstream signaling, such as Rac GTP loading and phosphorylation of PAK kinases, leading to increased phagocytosis of bacteria. Complementation of the CYRI-B knockout cells reverted the knockout phenotype. Our results unravel components of CEACAM3-initiated opsonin-independent phagocytosis on a genome-wide level and highlight CYRI-B as a negative regulator of CEACAM3-initiated signaling in myeloid cells.
MeSH term(s)	Humans ; Carcinoembryonic Antigen/genetics ; Carcinoembryonic Antigen/metabolism ; Opsonin Proteins ; Phagocytosis/genetics ; Cell Adhesion Molecules/genetics ; Bacteria/metabolism ; Guanosine Triphosphate
Chemical Substances	Carcinoembryonic Antigen ; Opsonin Proteins ; Cell Adhesion Molecules ; Guanosine Triphosphate (86-01-1) ; CEACAM3 protein, human
Language	English
Publishing date	2023-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.260771
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Article ; Online: CEACAM3-A Prim(at)e Invention for Opsonin-Independent Phagocytosis of Bacteria.

Bonsignore, Patrizia / Kuiper, Johannes W P / Adrian, Jonas / Goob, Griseldis / Hauck, Christof R

Frontiers in immunology

2020 Volume 10, Page(s) 3160

Abstract: Phagocytosis is one of the key innate defense mechanisms executed by specialized cells in multicellular animals. Recent evidence suggests that a particular phagocytic receptor expressed by human polymorphonuclear granulocytes, the carcinoembryonic ... ...

Abstract	Phagocytosis is one of the key innate defense mechanisms executed by specialized cells in multicellular animals. Recent evidence suggests that a particular phagocytic receptor expressed by human polymorphonuclear granulocytes, the carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3), is one of the fastest-evolving human proteins. In this focused review, we will try to resolve the conundrum why a conserved process such as phagocytosis is conducted by a rapidly changing receptor. Therefore, we will first summarize the biochemical and structural details of this immunoglobulin-related glycoprotein in the context of the human CEACAM family. The function of CEACAM3 for the efficient, opsonin-independent detection and phagocytosis of highly specialized, host-restricted bacteria will be further elaborated. Taking into account the decisive role of CEACAM3 in the interaction with pathogenic bacteria, we will discuss the evolutionary trajectory of the CEACAM3 gene within the primate lineage and highlight the consequences of CEACAM3 polymorphisms in human populations. From a synopsis of these studies, CEACAM3 emerges as an important component of human innate immunity and a prominent example of a dedicated receptor for professional phagocytosis.
MeSH term(s)	Animals ; Bacteria/immunology ; Biological Evolution ; Carcinoembryonic Antigen/genetics ; Carcinoembryonic Antigen/immunology ; Humans ; Immunity, Innate/genetics ; Immunity, Innate/immunology ; Phagocytosis/genetics ; Phagocytosis/immunology ; Primates
Chemical Substances	CEACAM3 protein, human ; Carcinoembryonic Antigen
Language	English
Publishing date	2020-02-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.03160
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Detection of SARS-CoV-2 from raw patient samples by coupled high temperature reverse transcription and amplification.

Kuiper, Johannes W P / Baade, Timo / Kremer, Marcel / Kranaster, Ramon / Irmisch, Linda / Schuchmann, Marcus / Zander, Johannes / Marx, Andreas / Hauck, Christof R

PloS one

2020 Volume 15, Issue 11, Page(s) e0241740

Abstract: SARS-CoV-2 is spreading globally with unprecedented consequences for modern societies. The early detection of infected individuals is a pre-requisite to contain the virus. Currently, purification of RNA from patient samples followed by RT-PCR is the gold ...

Abstract	SARS-CoV-2 is spreading globally with unprecedented consequences for modern societies. The early detection of infected individuals is a pre-requisite to contain the virus. Currently, purification of RNA from patient samples followed by RT-PCR is the gold standard to assess the presence of this single-strand RNA virus. However, these procedures are time consuming, require continuous supply of specialized reagents, and are prohibitively expensive in resource-poor settings. Here, we report an improved nucleic-acid-based approach to detect SARS-CoV-2 with the ability to detect as little as five viral genome equivalents. The approach delivers results without the need to purify RNA, reduces handling steps, minimizes costs, and allows evaluation by non-specialized equipment. The use of unprocessed swap samples is enabled by employing a heat-stable RNA- and DNA-dependent DNA polymerase, which performs the double task of stringent reverse transcription of RNA at elevated temperatures as well as PCR amplification of a SARS-CoV-2 specific target gene. As results are obtained within 2 hours and can be read-out by a hand-held LED-screen, this novel protocol will be of particular importance for large-scale virus surveillance in economically constrained settings.
MeSH term(s)	Betacoronavirus/genetics ; Betacoronavirus/isolation & purification ; COVID-19 ; Coronavirus Infections/diagnosis ; Coronavirus Infections/virology ; Humans ; Nasopharynx/virology ; Pandemics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/virology ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Reverse Transcriptase Polymerase Chain Reaction/methods ; SARS-CoV-2 ; Temperature
Chemical Substances	RNA, Viral
Keywords	covid19
Language	English
Publishing date	2020-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0241740
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Article ; Online: Self-Collected Gargle Lavage Allows Reliable Detection of SARS-CoV-2 in an Outpatient Setting.

Zander, Johannes / Scholtes, Stephan / Ottinger, Maximilian / Kremer, Marcel / Kharazi, Azadeh / Stadler, Vanessa / Bickmann, Julia / Zeleny, Christian / Kuiper, Johannes W P / Hauck, Christof R

Microbiology spectrum

2021 Volume 9, Issue 1, Page(s) e0036121

Abstract: Current procurement of specimens for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection requires trained personnel and dedicated equipment. We compared standard nasopharyngeal swabs with self-collected gargle lavage fluid obtained ... ...

Abstract	Current procurement of specimens for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection requires trained personnel and dedicated equipment. We compared standard nasopharyngeal swabs with self-collected gargle lavage fluid obtained from 80 mostly symptomatic outpatients. After RNA extraction, RT-PCR to detect SARS-CoV-2 was performed. Qualitative results obtained with the paired samples from individual outpatients were 100% congruent. Therefore, self-collected gargle lavage fluid can serve as a suitable specimen for coronavirus disease 2019 (COVID-19) testing in outpatients.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; COVID-19/diagnosis ; COVID-19 Testing/methods ; Female ; Humans ; Male ; Middle Aged ; Nasopharynx/virology ; Outpatients ; Pandemics ; SARS-CoV-2/isolation & purification ; Specimen Handling/methods ; Therapeutic Irrigation/methods ; Young Adult
Language	English
Publishing date	2021-07-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/Spectrum.00361-21
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Article ; Online: Detection of SARS-CoV-2 from raw patient samples by coupled high temperature reverse transcription and amplification

Kuiper, Johannes W. P. / Baade, Timo / Kremer, Marcel / Kranaster, Ramon / Irmisch, Linda / Schuchmann, Marcus / Zander, Johannes / Marx, Andreas / Hauck, Christof R.

PLOS ONE

2020 Volume 15, Issue 11, Page(s) e0241740

Keywords	General Biochemistry, Genetics and Molecular Biology ; General Agricultural and Biological Sciences ; General Medicine ; covid19
Language	English
Publisher	Public Library of Science (PLoS)
Publishing country	us
Document type	Article ; Online
ISSN	1932-6203
DOI	10.1371/journal.pone.0241740
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Importance of complete response for outcomes of pregnancy in patients with autoimmune hepatitis.

Fischer, Susan E / de Vries, Elsemieke S / Tushuizen, Maarten E / de Boer, Ynto S / van der Meer, Adriaan J P / de Man, Robert A / Brouwer, Johannes T / Kuyvenhoven, Johan P / Klemt-Kropp, Michael / Gevers, Tom J G / Tjwa, Eric T T L / Kuiper, Edith M M / Verhagen, Marc A M T / Friederich, Philip W / van Hoek, Bart

Liver international : official journal of the International Association for the Study of the Liver

2023 Volume 43, Issue 4, Page(s) 855–864

Abstract: Background and aims: While some articles describe outcome of pregnancy in autoimmune hepatitis (AIH), there are less data evaluating influence of AIH control on maternal and perinatal outcomes. This study analysed outcomes of pregnancy and related ... ...

Abstract	Background and aims: While some articles describe outcome of pregnancy in autoimmune hepatitis (AIH), there are less data evaluating influence of AIH control on maternal and perinatal outcomes. This study analysed outcomes of pregnancy and related possible risk factors in AIH. Method: A retrospective multicentre cohort study on pregnancy in AIH was performed in 11 hospitals in the Netherlands. Maternal and neonatal outcomes were collected from records and completed by interview. Risk factors-including incomplete response, relapse and cirrhosis-for adverse outcomes were identified using logistic regression analysis. Results: Ninety-seven pregnancies in 50 women resulted in 70 deliveries (72%) with a live birth rate of 98.5%. AIH relapse occurred in 6% during pregnancy, and in 27% of post-partum episodes. Absence of complete biochemical response at conception was identified as risk factor for the occurrence of gestational and post-partum relapses. Relapse of AIH in the year before conception was a risk factor for the occurrence of both gestational relapses and post-partum relapses. No complete biochemical response increased the risk for hypertensive disorders during pregnancy and intrahepatic cholestasis of pregnancy (ICP). Cirrhosis was found to be a risk factor for miscarriages, but not for other outcomes. Conclusion: Pregnancy in AIH is related to an increased incidence of maternal and fetal/neonatal complications; in most cases, outcome is good. Incomplete biochemical response at conception or relapse in the year before conception are risk factors for gestational and post-partum relapses, for hypertensive disorders and for ICP. Cirrhosis was a risk factor for miscarriages.
MeSH term(s)	Pregnancy ; Infant, Newborn ; Humans ; Female ; Abortion, Spontaneous ; Hypertension, Pregnancy-Induced ; Cohort Studies ; Hepatitis, Autoimmune/complications ; Hepatitis, Autoimmune/epidemiology ; Pregnancy Complications/epidemiology ; Liver Cirrhosis/complications ; Fibrosis ; Pregnancy Outcome ; Retrospective Studies
Language	English
Publishing date	2023-01-13
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ZDB-ID	2102783-3
ISSN	1478-3231 ; 1478-3223
ISSN (online)	1478-3231
ISSN	1478-3223
DOI	10.1111/liv.15511
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Article ; Online: Detection of SARS-CoV-2 from raw patient samples by coupled high temperature reverse transcription and amplification

Kuiper, Johannes W.P. / Baade, Timo / Kremer, Marcel / Kranaster, Ramon / Irmisch, Linda / Schuchmann, Marcus / Zander, Johannes / Marx, Andreas / Hauck, Christof R

medRxiv

Abstract: The SARS-CoV-2 beta coronavirus is spreading globally with unprecedented consequences for modern societies. The early detection of infected individuals is a pre-requisite for all strategies aiming to contain the virus. Currently, purification of RNA from ...

Abstract	The SARS-CoV-2 beta coronavirus is spreading globally with unprecedented consequences for modern societies. The early detection of infected individuals is a pre-requisite for all strategies aiming to contain the virus. Currently, purification of RNA from patient samples followed by RT-PCR is the gold standard to assess the presence of this single-strand RNA virus. However, these procedures are time consuming, require continuous supply of specialized reagents, and are prohibitively expensive in resource-poor settings. Here, we report an improved nucleic-acid-based approach to detect SARS-CoV-2, which alleviates the need to purify RNA, reduces handling steps, minimizes costs, and allows evaluation by non-specialized equipment. The use of unprocessed swap samples and the ability to detect as little as three viral genome equivalents is enabled by employing a heat-stable RNA- and DNA-dependent DNA polymerase, which performs the double task of stringent reverse transcription of RNA at elevated temperatures as well as PCR amplification of a SARS-CoV-2 specific target gene. As results are obtained within 2 hours and can be read-out by a hand-held LED-screen, this novel protocol will be of particular importance for large-scale virus surveillance in economically constrained settings.
Keywords	covid19
Language	English
Publishing date	2020-05-22
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.05.19.20103150
Database	COVID19

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Article ; Online: Detection of SARS-CoV-2 from raw patient samples by coupled high temperature reverse transcription and amplification.

Johannes W P Kuiper / Timo Baade / Marcel Kremer / Ramon Kranaster / Linda Irmisch / Marcus Schuchmann / Johannes Zander / Andreas Marx / Christof R Hauck

PLoS ONE, Vol 15, Iss 11, p e

2020 Volume 0241740

Abstract	SARS-CoV-2 is spreading globally with unprecedented consequences for modern societies. The early detection of infected individuals is a pre-requisite to contain the virus. Currently, purification of RNA from patient samples followed by RT-PCR is the gold standard to assess the presence of this single-strand RNA virus. However, these procedures are time consuming, require continuous supply of specialized reagents, and are prohibitively expensive in resource-poor settings. Here, we report an improved nucleic-acid-based approach to detect SARS-CoV-2 with the ability to detect as little as five viral genome equivalents. The approach delivers results without the need to purify RNA, reduces handling steps, minimizes costs, and allows evaluation by non-specialized equipment. The use of unprocessed swap samples is enabled by employing a heat-stable RNA- and DNA-dependent DNA polymerase, which performs the double task of stringent reverse transcription of RNA at elevated temperatures as well as PCR amplification of a SARS-CoV-2 specific target gene. As results are obtained within 2 hours and can be read-out by a hand-held LED-screen, this novel protocol will be of particular importance for large-scale virus surveillance in economically constrained settings.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases: Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group.

Bond, Marinde J G / Kuiper, Babette I / Bolhuis, Karen / Komurcu, Aysun / van Amerongen, Martinus J / Chapelle, Thiery / Dejong, Cornelis H C / Engelbrecht, Marc R W / Gerhards, Michael F / Grünhagen, Dirk J / van Gulik, Thomas / Hermans, John J / de Jong, Koert P / Klaase, Joost M / Kok, Niels F M / Leclercq, Wouter K G / Liem, Mike S L / van Lienden, Krijn P / Molenaar, I Quintus /

Neumann, Ulf P / Patijn, Gijs A / Rijken, Arjen M / Ruers, Theo M / Verhoef, Cornelis / de Wilt, Johannes H W / Kazemier, Geert / May, Anne M / Punt, Cornelis J A / Swijnenburg, Rutger-Jan

Annals of surgical oncology

2023 Volume 30, Issue 9, Page(s) 5376–5385

Abstract: ... 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ...

Abstract	Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study. Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons. Results: A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0-12% and 27-62%, and for permanently unresectable CRLM between 3-40% and 6-47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients. Conclusion: Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice.
MeSH term(s)	Humans ; Colorectal Neoplasms/pathology ; Liver Neoplasms/surgery ; Liver Neoplasms/drug therapy ; Hepatectomy/methods
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-023-13510-7
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