The c.1291A Allele Leads to a Loss of Membrane Expression and Mimics a CD177-Null Phenotype.

CD177 is a glycosyl phosphatidyl inositol (GPI)-linked, neutrophil-specific glycoprotein that in 3-5% of normal individuals is absent from all neutrophils. The molecular mechanism behind the absence of CD177 has not been unravelled completely. Here, we analyse the impact of the recently described c.

analysis of anti-HPA-1a dependent platelet phagocytosis and its inhibition using a new whole blood phagocytosis assay (WHOPPA).

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a serious bleeding condition mostly caused by the reaction between maternal anti-HPA-1a antibodies and fetal platelets. This reaction leads to Fc-dependent platelet phagocytosis. Although several serological methods have been developed to identify maternal antibodies, a reliable laboratory parameter as a prognostic tool for FNAIT severity is still lacking.

Production of recombinant humanized monoclonal anti-human neutrophil antigen (HNA) antibodies with potential applicability as standard antibodies.

Background: Antibodies against human neutrophil antigen (HNA) are involved in the pathogenesis of neonatal alloimmune neutropenia, autoimmune neutropenia, and transfusion-related acute lung injury. The present methods for anti-HNA antibody identification strongly depend on the presence of standard antisera with known allo/isospecificities. Here, we aimed to produce recombinant humanized antibodies to HNA from available mouse monoclonal antibodies (MoAbs).

World human neutrophil antigens investigation survey.

Background And Objectives: Human neutrophil antigens (HNAs) are categorized into five systems: HNA-1 to HNA-5. Given the importance of neutrophils in immunity, we sought to create awareness of the role of HNA diagnostic services in managing immune neutropenia and transfusion-related acute lung injury. To provide health communities all around the world with access to these services, we conducted a survey to create a directory of these HNA diagnostic services.

Fetal and neonatal alloimmune thrombocytopenia: No evidence of systemic inflammation as a modulator of disease severity. Could placental inflammation be key?

In fetal/neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies against paternal human platelet antigens (HPA) cross the placenta and lead to platelet destruction. The extent of thrombocytopenia varies among neonates, and inflammation may constitute an important trigger. A set of stable inflammatory markers was measured in serum samples from neonates with low platelet counts, of which n = 50 were diagnosed with FNAIT due to anti-HPA-1a antibodies and n = 50 were thrombocytopenic without detectable maternal HPA antibodies.

Anti-human neutrophil antigen-1d specificity is frequently observed in anti-human neutrophil antigen-1b alloantisera.

Background: Four amino acids are involved in epitope formation of human neutrophil antigens (HNA)-1 alleles, located at positions 36, 65, 78, and 82. HNA-1a and HNA-1b alloantibody epitopes were recently characterized. The HNA-1b allele also carries the HNA-1d epitope p.

Human Neutrophil Antigen Genotype and Allele Frequencies in Iranian Blood Donors.

Objective: Human neutrophil antigens (HNAs) can be targeted by HNA-allo antibodies and cause a variety of clinical conditions such as transfusion-related acute lung injury (TRALI) and neonatal alloimmune neutropenia (NAIN). The current study is aimed at identifying the genotype and allele frequencies of HNAs in Iranian blood donors.

Methods: A total of 150 blood samples were obtained from healthy blood donors.

Identification of Antibodies against Neutrophil Surface Antigens in Two Iranian Patients with Autoimmune Neutropenia.

Autoimmune neutropenia is a type of immune-mediated neutropenia, caused by antibody-induced neutrophil destruction. Here we report two cases (3-year-old boy and 9-year-old girl) with suspected autoimmune neutropenia. The presence of neutrophil antibodies in sera of these patients was investigated using standard neutrophil antibody screening tests such as granulocyte immunofluorescence test (GIFT), granulocyte agglutination test (GAT), and lymphocyte immunofluorescence test (LIFT).

Transfusion of target antigens to preimmunized recipients: a new mechanism in transfusion-related acute lung injury.

Transfusion-related lung injury (TRALI) is a serious side effect of blood transfusion. Exclusion of antibody carriers from the donor pool has significantly decreased the number of cases, but TRALI remains the leading cause of transfusion-related morbidity and mortality in industrialized countries. Here, we show that proteins released from donor cells during processing of blood components are capable of inducing a new type of reverse TRALI when transfused to preimmunized recipients.

Self-rated vocal complaints relationship to Vocal Tract Discomfort and Singers Voice Handicap Index in Iranian religious singers.

Purpose: The religious singing is a popular group of professional voice users in Iran which is performed in a sadness form to persuade the audiences to cry and think to holy persons. This style has its own unique vocal demands and abuses. Therefore, the present study, for the first time, aimed to investigate the prevalence of self-reported vocal complaints, vocal discomfort symptoms, and its effects on the vocal-related life of the Iranian religious singers.

Characterization of CD177-reactive iso- and auto-antibodies.

Background: CD177 is a surface protein on neutrophils and a main mediator for the surface expression of proteinase 3 (PR3). Its functions are largely unknown. At least three types of antibodies have been described to target CD177: isoantibodies, which are formed in CD177-null individuals as a result of an immune reaction following transfusion or pregnancy; autoantibodies present in sera from patients with autoimmune neutropenia; and antineutrophil cytoplasmic antibodies in sera from patients with glomerulonephritis with polyangiitis.

Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms.

Background: The human neutrophil antigen 2 (HNA-2), which is expressed on CD177, is undetectable in 3-5% of the normal population. Exposure of these HNA-2 individuals to HNA-2-positive cells can cause immunization and pro-duction of HNA-2 antibodies, which can induce immune neutropenia and transfusion-related acute lung injury. In HNA-2-positive individuals, neutrophils are divided into a CD177 and a CD177 subpopulation.

Immunization against α β and α β in Glanzmann thrombasthenia patients carrying the French Gypsy mutation.

Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal α β carrying HPA-1b epitopes.

Naturally occurring point mutation Cys460Trp located in the I-EGF1 domain of integrin β3 alters the binding of some anti-HPA-1a antibodies.

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of platelets in the fetus or newborn by maternal platelet alloantibodies, mostly against human platelet antigen (HPA)-1a. Recent studies indicate that two anti-HPA subtypes exist: Type I reacts with epitopes residing on the plexin-semaphorin-integrin (PSI) and type II with plexin-semaphorin-integrin/integrin epidermal growth factor 1 (I-EGF1) domains of the β3 integrin. Here, we evaluated whether a Cys460Trp mutation in the I-EGF1 domain found in a patient with Glanzmann thrombasthenia can alter the binding of anti-HPA-1a.

Primary structure of human neutrophil antigens 1a and 1b.

Background: Neutrophil specific Fcγ receptor IIIb (CD16b) is a low-affinity IgG receptor. Its polymorphic variants are associated with human neutrophil antigens (HNA). HNA-1a and HNA-1b differ in four amino acids.

Maternal antibodies against paternal class I human leukocyte antigens are not associated with foetal and neonatal alloimmune thrombocytopenia.

The causative role of maternal, anti-human leukocyte antigen (anti-HLA) class I antibodies in foetal and neonatal alloimmune thrombocytopenia (FNAIT) remains controversial. Furthermore, in FNAIT cases caused by anti-human platelet antigen-1a (anti-HPA-1a) antibodies, the possible additive effect of maternal anti-HLA class I antibodies on outcomes is unclear. Among 817 mother-father-neonate trios of suspected FNAIT, we assessed the possible association of maternal anti-HLA class I antibodies with neonatal platelet count, and the incidence of FNAIT caused by anti-HPA-1a antibodies.

Current Anti-HPA-1a Standard Antibodies React with the β3 Integrin Subunit but not with αIIbβ3 and αvβ3 Complexes.

Background:  Fetal/neonatal alloimmune thrombocytopenia (FNAIT) results from maternal alloantibodies (abs) reacting with fetal platelets expressing paternal human platelet antigens (HPAs), mostly HPA-1a. Anti-HPA-1a abs, are the most frequent cause of severe thrombocytopenia and intracranial hemorrhage (ICH).

Objectives:  Titration of anti-HPA-1a in maternal serum using standard National Institute for Biological Standards and Control (NIBSC) 03/152 is one diagnostic approach to predict the severity of FNAIT.

Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia.

Platelet autoantibody-induced platelet clearance represents a major pathomechanism in immune thrombocytopenia (ITP). There is growing evidence for clinical differences between anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib/IX mediated ITP. Glycoprotein V is a well characterized target antigen in Varicella-associated and drug-induced thrombocytopenia.

The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency.

Background: Human neutrophil antigen-2 (HNA-2) is exclusively expressed on neutrophils. HNA-2-deficient individuals (HNA-2 null) are susceptible to produce isoantibodies. The nonsense CD177 coding single-nucleotide polymorphism (SNP) c.

A sequence-specific polymerase chain reaction method for HNA-2 genotyping: homozygous c.843A>T mutation predicts the absence of CD177.

Background: Human neutrophil antigen-2 is located on a glycosylphosphatidylinositol-anchored receptor, CD177. Humans not expressing CD177 on their neutrophils may, under defined conditions, form isoantibodies. The genetic background for the absence of CD177 is not fully understood, and genetic screening of patients and donors is currently unavailable.