NB1, a new neutrophil-specific antigen involved in the pathogenesis of neonatal neutropenia

Lalezari, Parviz; Murphy, Georgette B.; Allen, Fred H.

doi:10.1172/jci106582

Cited by 143 publications

(117 citation statements)

References 7 publications

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“…Antibodies to CD177 can cause a variety of disorders, including alloimmune neonatal neutropenia, autoimmune neutropenia, immune neutropenia after bone marrow transplantation, drug-induced immune neutropenia, transfusion-related lung injury, essential thrombocythemia, and myeloproliferative diseases. 33,34 Although it was first described as a neutrophil-specific antigen linked to neonatal alloimmune neutropenia, 35 to our knowledge, this is the first time that this gene is reported as a biomarker for sepsis in neonates.…”

Section: Discussionmentioning

confidence: 94%

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

et al. 2014

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BACKGROUND: Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences. METHODS: This was a prospective observational double-cohort study conducted in VLBW (<1500 g) infants with culture-positive bacterial sepsis and non-septic matched controls. Blood samples were collected as soon as clinical signs of sepsis were identified and before antibiotics were initiated. Total RNA was processed for genome-wide expression analysis using Affymetrix gene arrays. RESULTS: During a 19-month period, 17 septic VLBW infants and 19 matched controls were enrolled. First, a three-dimensional unsupervised principal component analysis based on the entire genome (28 000 transcripts) identified 3 clusters of patients based on gene expression patterns: Gram-positive sepsis, Gram-negative sepsis, and noninfected control infants. Furthermore, these groups were confirmed by using analysis of variance, which identified a transcriptional signature of 554 of genes. These genes had a significantly different expression among the groups. Of the 554 identified genes, 66 belonged to the tumor necrosis factor and 56 to cytokine signaling. The most significantly overexpressed pathways in septic neonates related with innate immune and inflammatory responses and were validated by real-time reverse transcription polymerase chain reaction. CONCLUSIONS: Our preliminary results suggest that genome-wide expression profiles discriminate septic from nonseptic VLBW infants early in the neonatal period. Further studies are needed to confirm these findings.

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Section: Discussionmentioning

confidence: 94%

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

et al. 2014

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“…During pregnancy, women with a CD177 null phenotype are prone to produce alloantibodies against CD177 that cross the placenta, react with fetal neutrophils, and cause neutropenia of the newborn. This mechanism let to the initial discovery of the NB1 antigen in 1971 (7). Alloantibodies to CD177, present in blood products obtained from immunized donors, have also been implicated as mediators of transfusionrelated acute lung injury (8).…”

mentioning

confidence: 99%

The Neutrophil-specific Antigen CD177 Is a Counter-receptor for Platelet Endothelial Cell Adhesion Molecule-1 (CD31)

Sachs

Andrei-Selmer

Maniar

et al. 2007

Journal of Biological Chemistry

202

199

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Human neutrophil-specific CD177 (NB1 and PRV-1) has been reported to be up-regulated in a number of inflammatory settings, including bacterial infection and granulocyte-colonystimulating factor application. Little is known about its function. By flow cytometry and immunoprecipitation studies, we identified platelet endothelial cell adhesion molecule-1 (PECAM-1) as a binding partner of CD177. Real-time proteinprotein analysis using surface plasmon resonance confirmed a cation-dependent, specific interaction between CD177 and the heterophilic domains of PECAM-1. Monoclonal antibodies against CD177 and against PECAM-1 domain 6 inhibited adhesion of U937 cells stably expressing CD177 to immobilized PECAM-1. Transendothelial migration of human neutrophils was also inhibited by these antibodies. Our findings provide direct evidence that neutrophil-specific CD177 is a heterophilic binding partner of PECAM-1. This interaction may constitute a new pathway that participates in neutrophil transmigration.CD177 (NB1 and PRV-1) is a 58-to 64-kDa glycosylphosphatidylinositol-anchored glycoprotein expressed exclusively by neutrophils, neutrophilic metamyelocytes, and myelocytes, but not by any other blood cells (1, 2). We and others elucidated its primary structure by sequencing the NB1 and PRV-1 genes, which later turned out to be two alleles of a single CD177 gene (3-5). The surface expression of CD177 is unique in that only a subpopulation of neutrophils expresses this protein on the cell surface, with the mean size of the CD177-positive subpopulation ranging from 45% to 65% (2, 6).CD177 has been well studied as a target antigen in immunemediated disorders. During pregnancy, women with a CD177 null phenotype are prone to produce alloantibodies against CD177 that cross the placenta, react with fetal neutrophils, and cause neutropenia of the newborn. This mechanism let to the initial discovery of the NB1 antigen in 1971 (7). Alloantibodies to CD177, present in blood products obtained from immunized donors, have also been implicated as mediators of transfusionrelated acute lung injury (8).Although well characterized as an immunotarget, the function of CD177 is largely unknown. It has been reported that CD177 is up-regulated on the neutrophil surface upon stimulation, including during severe bacterial infections, and following granulocyte-colony-stimulating factor treatment (9). In addition, antibody-mediated clustering of CD177 primes the N-formyl-methionyl-leucyl-phenylalanine (fMLP) 3 -activated respiratory burst reaction of the neutrophil (8). Taken together, these observations make it reasonable to suppose that CD177 may be involved in processes of neutrophil-mediated host defense. One preliminary study suggests a participation of CD177 in neutrophil-endothelial cell interaction (10). The latter observation is in line with the fact that CD177, as a member of the leukocyte antigen-6 superfamily, shares a similar structure with the urokinase plasminogen activator receptor (11). Urokinase plasminogen activator receptor is expr...

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“…CD177, also known as Polycythemia Vera protein-1 (PRV-1), is a glycoprotein that was first discovered in 1970 in connection with studies of Polycythemia Vera (Lalezari, 1971). It belongs to the Leukocyte Antigen 6 (Ly-6) supergene family and is the best characterized member of this family (Caruccio, 2006).…”

Section: Mpr3 and Cd177mentioning

confidence: 99%

The Role of Proteinase 3 and Neutrophils in ANCA-Associated Systemic Vasculitis

AbdGawad¹

2011

Advances in the Etiology, Pathogenesis and Pathology of Vasculitis

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NB1, a new neutrophil-specific antigen involved in the pathogenesis of neonatal neutropenia

Cited by 143 publications

References 7 publications

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

The Neutrophil-specific Antigen CD177 Is a Counter-receptor for Platelet Endothelial Cell Adhesion Molecule-1 (CD31)

The Role of Proteinase 3 and Neutrophils in ANCA-Associated Systemic Vasculitis

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