Biomedical subjects

David F Stroncek

Publications and source records attributed to David F Stroncek.

At least 19 recordsLinked to original sources

PubMed2007

Pancreatic islet cell therapy for type I diabetes: understanding the effects of glucose stimulation on islets in order to produce better islets for transplantation.

While insulin replacement remains the cornerstone treatment for type I diabetes mellitus (T1DM), the transplantation of pancreatic islets of Langerhans has the potential to become an important alternative. And yet, islet transplant therapy is limited by several factors, including far too few donor pancreases. Attempts to expand mature islets or to produce islets from stem cells are far from clinical application. The production and expansion of the insulin-producing cells within the islet (so called beta cells), or even creating cells that secrete insulin under appropriate physiological control, has proven difficult. The difficulty is explained, in part, because insulin synthesis and release is complex, unique, and not entirely characterized. Understanding beta-cell function at the molecular level will likely facilitate the development of techniques to manufacture beta-cells from stem cells. We will review islet transplantation, as well as the mechanisms underlying insulin transcription, translation and glucose stimulated insulin release.

Animals↗

PubMed2007

Pulmonary transfusion reactions.

Transfusion reactions remain a common complication of transfusion therapy; reactions affecting the lungs are some of the most serious. Several different mechanisms are responsible for pulmonary transfusion reactions, and most cause adverse effects in addition to lung injury. Fluid overload can lead to pulmonary edema, antibodies reacting with plasma proteins can cause bronchospasm and anaphylaxis, and particulate matter can produce microemboli. These reactions are well understood and usually can be prevented. Transfusions are also associated with acute lung injury and acute respiratory distress syndrome (ARDS), but their etiology is poorly understood and they remain clinically problematic. Neutrophil antibodies cause some of these serious as well as mild pulmonary reactions, but the exact role of leukocyte antibodies in pulmonary reactions remains unclear. Other blood donor, blood component, and transfusion recipient factors likely play a contributing or modulating role in pulmonary transfusion reactions, but prospective studies are needed to better understand their role.

Blood Component Transfusion↗

PubMed2006

Comprehensive epitope mapping of the Epstein-Barr virus latent membrane protein-2 in normal, non tumor-bearing individuals.

Latent membrane protein (LMP)-2 is one of the Epstein-Barr virus (EBV)-encoded proteins consistently expressed by nasopharyngeal carcinoma (NPC). EBV-transformed lymphoblastoid cell lines (LCL) have been used in patients with NPC to induce LMP-2-recognizing T cell lines which have been in turn utilized for protein-wide mapping of T cell epitopes. However, comprehensive mapping of naturally recognized LMP-2 epitopes in non tumor-bearing individuals has not been reported. Here, we applied a low sensitivity epitope-defining technique for the identification of LMP-2 CTL responses detectable ex vivo in EBV-experienced individuals. This screening tool has been previously validated by analyzing memory CTL responses to Flu, cytomegalovirus (CMV), and the melanoma associated antigen gp100/Mel17. Peripheral blood monocytes (PBMC) from ten Caucasian and ten Chinese individuals were stimulated ex vivo with pools of nonamer (9-mer) peptides overlapping in a stepwise fashion each single amino acid of the LMP-2 sequence. No obvious differences were observed between the immune response of the two ethnic groups save for those related to the divergence in the ethnic prevalence of HLA haplotypes. Several novel and known LMP-2 epitopes were identified. Reactivity toward at least one LMP-2 epitope was detected in 18 of the 20 donors but no prevalent human leukocyte antigen (HLA)/epitope combination was observed confirming that LMP-2 reactivity in the context of common HLA alleles is more pleiotropic than that of FLU and CMV. We believe that the usefulness of these epitopes occurring naturally in non-cancer bearing patients as reagents for the immunization of patients with early or advanced stage NPC deserves further evaluation.

Amino Acid Sequence↗

PubMed2006

Recent advances in the bcr-abl negative chronic myeloproliferative diseases.

The chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders of unknown etiology. In one of these (chronic myeloid leukemia), there is an associated pathognomonic chromosomal abnormality known as the Philadelphia chromosome. This leads to constitutive tyrosine kinase activity which is responsible for the disease and is used as a target for effective therapy. This review concentrates on the search in the other conditions (polycythemia vera, essential thrombocythemia and idiopathic mylofibrosis) for a similar biological marker with therapeutic potential. There is no obvious chromosomal marker in these conditions and yet evidence of clonality can be obtained in females by the use of X-inactivation patterns. PRV-1mRNA over expression, raised vitamin B12 levels and raised neutrophil alkaline phosphatase scores are evidence that cells in these conditions have received excessive signals for proliferation, maturation and reduced apoptosis. The ability of erythroid colonies to grow spontaneously without added external erythropoietin in some cases, provided a useful marker and a clue to this abnormal signaling. In the past year several important discoveries have been made which go a long way in elucidating the involved pathways. The recently discovered JAK2 V617F mutation which occurs in the majority of cases of polycythemia vera and in about half of the cases with the two other conditions, enables constitutive tyrosine kinase activity without the need for ligand binding to hematopoietic receptors. This mutation has become the biological marker for these conditions and has spurred the development of a specific therapy to neutralize its effects. The realization that inherited mutations in the thrombopoietin receptor (c-Mpl) can cause a phenotype of thrombocytosis such as in Mpl Baltimore (K39N) and in a Japanese family with S505A, has prompted the search for acquired mutations in this receptor in chronic myeloproliferative disease. Recently, two mutations have been found; W515L and W515K. These mutations have been evident in patients with essential thrombocythemia and idiopathic myelofibrosis but not in polycythemia vera. They presumably act by causing constitutional, activating conformational changes in the receptor. The discovery of JAK2 and Mpl mutations is leading to rapid advancements in understanding the pathophysiology and in the treatment of these diseases.

Journal Article↗

PubMed2006

Comparison of proteomic profiles of serum, plasma, and modified media supplements used for cell culture and expansion.

BACKGROUND: The culture and expansion of human cells for clinical use requires the presence of human serum or plasma in culture media. Although these supplements have been extensively characterized in their chemical composition, only recently it has been possible to provide by high throughput protein analysis, a comprehensive profile of the soluble factors contributing to cell survival. This study analyzed and compared the presence of 100 proteins including chemokines, cytokines and soluble factors in six different types of media supplements: serum, plasma, recalcified plasma, heat inactivated serum, heat inactivated plasma and heat inactivated recalcified plasma. METHODS: Serum, plasma, recalcified plasma, and heat inactivated supplements were prepared from ten healthy subjects. The levels of 100 soluble factors were measured in each sample using a multiplexed ELISA assay and compared by Eisen hierarchical clustering analysis. RESULTS: A comparison of serum and plasma levels of soluble factors found that 2 were greater in plasma but 18 factors were greater in serum including 11 chemokines. The levels of only four factors differed between recalcified plasma and plasma. Heat inactivation had the greatest effect on soluble factors. Supervised Eisen hierarchical clustering indicated that the differences between heat inactivated supplements and those that were not were greater than the differences within these two groups. The levels of 36 factors differed between heat inactivated plasma and plasma. Thirty one of these factors had a lower concentration in heat inactivated plasma including 12 chemokines, 4 growth factors, 4 matrix metalloproteases, and 3 adhesion molecules. Heat inactivated decalcified plasma is often used in place of heat inactivated serum and the levels of 19 soluble factors differed between these two supplements. CONCLUSION: Our report provides a comprehensive protein profile of serum, plasma recalcified plasma, and heat inactivated supplements. This profile represents a qualitative and quantitative database that can aid in the selection of the appropriate blood derived supplement for human cell cultures with special requirements.

Journal Article↗

PubMed2006

MHC-peptide specificity and T-cell epitope mapping: where immunotherapy starts.

The evaluation and characterization of epitope-specific human leukocyte antigen (HLA)-restricted memory T-cell reactivity is an important step for the development of preventive vaccines and peptide-based immunotherapies for viral and tumor diseases. The past decade has witnessed the use of HLA-restricted peptides as tools to activate strong immune responses of naïve or memory T cells specifically. This has fuelled an active search for methodological approaches focusing on HLA and peptide associations. Here, we outline new perspective on the emerging opportunity of evaluating HLA and peptide restriction by using novel approaches, such as quantitative real-time PCR, that can identify epitope specificities that are potentially useful in clinical settings.

Animals↗

PubMed2006

Streptococcus agalactiae sepsis after transfusion of a plateletpheresis concentrate: benefit of donor evaluation.

BACKGROUND: Bacterial contamination of platelet (PLT) components is an important cause of transfusion reactions. Recent efforts have focused on heightened surveillance to detect contamination before transfusion to limit recipient morbidity and mortality. Although identifying the cause of contamination is most often viewed in the context of recipient safety, this case illustrates the importance of a thorough evaluation on donor safety. CASE REPORT: A 68-year-old woman experienced a severe febrile reaction after a plateletpheresis transfusion. Blood cultures from the patient and from the plateletpheresis component were both positive for the presence of Streptococcus agalactiae. No abnormalities were identified on review of collection and processing records. The donor was asymptomatic and had a negative review of systems, a normal physical exam, normal laboratory values, and negative blood and urine cultures. One of three stool samples was positive for the presence of occult blood. Colonoscopy revealed a Dukes Stage B colonic adenocarcinoma. Fifteen months after surgical resection and adjuvant chemotherapy, the donor had no evidence of recurrent tumor. CONCLUSION: Identification of bacteria in blood components should trigger a comprehensive donor evaluation, particularly if donor bacteremia is suspected. Organisms that may be associated with an enteric source should prompt a thorough gastrointestinal evaluation. Because the primary reservoir of S. agalactiae in the human body is the gastrointestinal tract, and because no findings suggested an alternate portal of entry in our male donor, a gastrointestinal source was suspected. In this case, an evaluation for organism-specific pathology led to early identification of a potentially curable large bowel lesion.

Aged↗

PubMed2006

In vitro variables of red blood cell components collected by apheresis and frozen 6 and 14 days after collection.

BACKGROUND: An automated cell processing system (ACP 215, Haemonetics Corp.) can be used for the glycerolization and deglycerolization of RBC components, but the components must be 6 or fewer days old. Depending on the anticoagulant (CP2D)/additive solution (AS) used, deglycerolized RBCs can be stored at 1 to 6 degrees C for up to 14 days. This study evaluated in vitro variables of apheresis RBC stored for 6 and 14 days at 1 to 6 degrees C before glycerolization and 14 days after deglycerolization. STUDY DESIGN AND METHODS: Two units of CP2D/AS-3 leukoreduced RBCs were collected by apheresis from seven donors. One unit was glycerolized and frozen 6 days and the other 14 days after collection. All units were deglycerolized with the ACP 215 and stored at 1 to 6 degrees C for 14 days in AS-3. Several in vitro variables were evaluated during postdeglycerolization storage. RESULTS: All components had postdeglycerolization RBC recoveries greater than 81 percent and osmolalities of less than 400 mOsm per kg. No significant differences were noted in potassium and supernatant hemoglobin after 14 days of postdeglycerolization storage between RBCs frozen at 6 and 14 days after collection. After 14 days of postdeglycerolization storage, however, the pH, lactate, and ATP levels were slightly lower in RBCs frozen after 14 days. CONCLUSION: The ACP 215 can be used to glycerolize and deglycerolize apheresis RBC components that are up to 14 days of age. It is likely that apheresis components glycerolized at 14 days of age or less can be stored up to 14 days in AS-3 after deglycerolization, but this should be confirmed with in vivo survival studies.

Adenosine Triphosphate↗

PubMed2006

KEL6 and KEL7 genotyping with sequence-specific primers.

BACKGROUND: Although antibodies to Js(a) and Js(b) are clinically significant, reagent-quality anti-Js(a) and anti-Js(b) are not readily available. A sequence-specific primer-polymerase chain reaction (SSP-PCR) genotyping assay was tested that makes use of two single-nucleotide polymorphisms (SNPs) at positions 1910 and 2019 of KEL. These SNPs distinguish the gene encoding Js(a), KEL6; and Js(b), KEL7. STUDY DESIGN AND METHODS: Four primer sets that selectively amplified KEL6 and KEL7 from genomic DNA were developed. Two sets detected the SNP at bp 1910 and two sets detected the bp 2019 SNP. KEL6 and KEL7 genotyping and Js(a) and Js(b) phenotyping results were compared among 64 subjects. RESULTS: The SSP-PCRs were specific for KEL6 and KEL7 when testing DNA for three donors of known Js phenotype: Js(a+b-), Js(a-b+), and Js(a+b+). Genotyping results for the 1910 SNP were identical to the phenotyping results in all 64 subjects, but for the 2019 SNP, the genotyping and phenotyping results were identical for only 49 subjects. In 12 subjects with the Js(a-b+) phenotype, the 2019 SNP was heterozygous KEL6, KEL7; in 2 with Js(a-b+) and in 1 with Js(a+b+), the 2019 SNP was homozygous KEL6. CONCLUSION: KEL 2019-bp SNP does not always correlate with the Js phenotype owing to the presence of an atypical KEL gene with a KEL7 polymorphism at 1910 and a KEL6 polymorphism at 2019. The KEL polymorphism at 2019 is silent and this allele yields a Js(a-b+) phenotype. Only analysis of the 1910-bp SNP can be used to genotype KEL6 and KEL7.

Black or African American↗

PubMed2006

Effects of storage time and exogenous protease inhibitors on plasma protein levels.

Plasma biomarker analysis requires intact unbiased starting material. We analyzed the effects on plasma protein profiles of protease inhibitor cocktails and preprocessing storage. Plasma from 12 healthy subjects collected with and without protease inhibitors was prepared immediately and after 2 hours of room temperature storage. The samples were analyzed by a multiplexed enzyme-linked immunosorbent assay that captured 99 chemokines and cytokines. Unsupervised hierarchical analysis clustered the samples into 4 groups; one composed predominantly of samples processed immediately, another of samples processed after 2 hours, and the remaining two were a mix of immediate and 2-hour samples. The mixed and immediate group protein profiles were similar. However, among the immediate and 2-hour samples, the levels of 37 factors differed significantly: all were greater after 2 hours. The dramatic changes in protein levels during storage were independent of protease inhibitors and are likely due to cytokine production and/or release by leukocytes and platelets.

Blood Preservation↗

PubMed2005

The subcellular distribution of myeloid-related protein 8 (MRP8) and MRP14 in human neutrophils.

BACKGROUND: Myeloid-related protein 8 (MRP8) and MRP14 are S100 family calcium binding proteins that form a heterodimer known as calprotectin or MRP8/14 that is present in the cytosol of neutrophils and monocytes. MRP8/14 becomes associated with endothelium at sites of monocyte and neutrophil adhesion and transmigration and induces a thrombogenic and inflammatory response by increasing the endothelial transcription of proinflammatory chemokines and adhesion molecules. The distribution of MRP8/MRP14 among neutrophil granules and plasma membranes is unclear and was investigated to better understand the role of this molecule in acute inflammation. STUDY DESIGN: Three monoclonal antibodies specific for MRP8 and MRP14 were characterized and used in immunoblotting assays of neutrophil whole cell extracts, and isolated plasma membranes, primary granules, secondary granules and cytosol. RESULTS: MRP8 and MRP14 were detected in neutrophil cytosol, plasma membrane, primary granule and secondary granule fractions. MRP8/14 demonstrated a calcium-dependent adherence to plasma membranes and primary granules and could be removed by washing with EGTA in a high ionic strength buffer. In contrast, MRP8/14 was found within the contents of the secondary granules. Activated neutrophils released secondary granules and MRP8/14. CONCLUSION: MRP8/14 is located in neutrophil cytosol and secondary granule fractions and is loosely associated with plasma membranes. MRP8/14 released with secondary granules by activated neutrophils likely binds to endothelium and plays an important role in acute inflammation.

Journal Article↗

PubMed2005

Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms.

BACKGROUND: Interferon (IFN)-alpha is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs). This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS) stimulation in vitro. RESULTS: Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-beta, IFN-alpha2b/alpha2, IFN-alphaI, IFN-alpha2, IFN-alphaC, IFN-alphaJ1, IFN-alphaH2, and INF-alpha4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx)-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-gamma. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their sub-classification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. CONCLUSION: Seven IFN-alpha isoforms and IFN-beta participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-alpha in autoimmunity and tumor rejection by including and/or excluding an array of related factors likely to be heterogeneously expressed by distinct sub-populations of individuals in sickness or in response to biological therapy.

Journal Article↗

PubMed2005

Analysis of memory T lymphocyte activity following stimulation with overlapping HLA-A2402, A0101 and Cw*0402 restricted CMV pp65 peptides.

The continuous efforts aimed at the identification of new immune epitopes across the MHC system has led to the discovery that more than one peptide may be restricted to the same HLA antigen and function as an immune determinant for that association. The aim of this study was to compare the ability of two overlapping peptides, the nonamer (9-mer) cytomegalovirus (CMV) pp65341-349 (QYDPVAALF) and the decamer (10-mer) CMV pp65341-350 (QYDPVAALFF), and the esadecamer (16-mer) peptide containing both the 9-mer and 10-mer sequences, CMV pp65340-355 (RQYDPVAALFFFDIDL), to stimulate and maintain over time a T cell immune reactivation by HLA-A*2402, A*0101, and Cw*0402 cells from CMV-seropositive subjects. The 9-mer, 10-mer, and 16-mer peptides effectively stimulated CTLs from HLA-A*2402, HLA-A*0101, and HLA-Cw*0402 CMV seropositive donors. This data confirms that both the 9-mer and the 10-mer peptides are promiscuous and are not restricted to a single HLA antigen. CMV pp65341-349 and CMV pp65341-350 have the ability to produce CMV-specific CTLs in subjects with several different HLA types, presenting a practical advantage over other peptides that are restricted only to a single HLA antigen, and thus being optimal for CMV adoptive immune therapy. Moreover, since the 16-mer peptide encompasses both the 9-mer and 10-mer peptides, it may be better than either of these peptides for CMV adoptive immune therapy.

Journal Article↗

PubMed2005

The value of pH as a quality control indicator for apheresis platelets.

BACKGROUND: Standards and regulations require measurement of pH as an apheresis platelet (PLT) component quality monitor. The usefulness of this quality control (QC) measure was investigated. STUDY DESIGN AND METHODS: QC data were retrospectively reviewed for apheresis PLTs collected over 4.5 years. Three collection devices were used, the Amicus (Baxter), the CS-3000 Plus (Baxter), and the MCS+ LN9000 (Haemonetics). Each month, four components from each instrument were sampled. PLT counts and component volume were measured immediately after collection, and pH, after 5 days of storage. RESULTS: A total of 668 products were studied. pH decreased as PLT concentration increased (r(2) = 0.129, p < 0.001) and as component volume decreased (r(2) = 0.086, p = 0.02). PLT concentration and volume, however, were poor predictors of a low pH. Apheresis instrument type affected pH. The 216 components collected with use of the CS-3000 device had a lower pH than components from the other two instruments. Only 13 components had a pH value less than the acceptable level of 6.2, 12 of which were collected with the CS-3000. CONCLUSIONS: For newer-model blood cell separators, pH measurements do not provide information that might identify a manufacturing problem. Because factors that influence pH are controlled or monitored for each component, evaluation of pH on a sample group provides an indication of the quality of specific component only, rather than an effective monitor of the quality of the manufacturing process.

Blood Banks↗

PubMed2005

Factors affecting the formation of white particulate matter in red blood cell components.

BACKGROUND: Recently white particulate matter (WPM) in red blood cell (RBC) components has received increased attention. The nature and causes of WPM formation were investigated. STUDY DESIGN AND METHODS: Whole-blood units were collected from 18 healthy subjects with three different types of collection sets. Six units were collected into each type. Units were divided into four equal parts and stored for 4 hours: two parts at room temperature and two at 4 degrees C. RBCs were prepared from each quarter-unit: two by heavy centrifugation (5000 x g) and two by light centrifugation (2000 x g). Whole blood was inspected for WPM over 4 hours and RBCs over 1 hour. RESULTS: No WPM was detected in whole blood, but WPM was detected in at least one RBC component from 9 of the 18 donations. The 36 components prepared by heavy centrifugation were more likely to contain WPM than the 36 prepared by light centrifugation (50% vs. 19%; p < 0.02). The incidence of WPM was similar among RBCs stored at room temperature and 4 degrees C. Donors of RBCs with WPM had higher total cholesterol levels than donors of components without WPM (191 +/- 20 mg/dL vs. 163 +/- 32 mg/dL; p < 0.04), but there was no difference in triglyceride levels between the two groups. CONCLUSIONS: WPM is an expected consequence of standard RBC manufacturing methods, but it is more frequent in RBCs prepared by heavy centrifugation and from donors with higher cholesterol levels.

Adult↗

PubMed2004

Ambiguous allele combinations in HLA Class I and Class II sequence-based typing: when precise nucleotide sequencing leads to imprecise allele identification.

Sequence-based typing (SBT) is one of the most comprehensive methods utilized for HLA typing. However, one of the inherent problems with this typing method is the interpretation of ambiguous allele combinations which occur when two or more different allele combinations produce identical sequences. The purpose of this study is to investigate the probability of this occurrence. We performed HLA-A,-B SBT for Exons 2 and 3 on 676 donors. Samples were analyzed with a capillary sequencer. The racial distribution of the donors was as follows: 615-Caucasian, 13-Asian, 23-African American, 17-Hispanic and 8-Unknown. 672 donors were analyzed for HLA-A locus ambiguities and 666 donors were analyzed for HLA-B locus ambiguities. At the HLA-A locus a total of 548 total ambiguous allele combinations were identified (548/1344 = 41%). Most (278/548 = 51%) of these ambiguities were due to the fact that Exon 4 analysis was not performed. At the HLA-B locus 322 total ambiguous allele combinations were found (322/1332 = 24%). The HLA-B*07/08/15/27/35/44 antigens, common in Caucasians, produced a large portion of the ambiguities (279/322 = 87%). A large portion of HLA-A and B ambiguous allele combinations can be addressed by utilizing a group-specific primary amplification approach to produce an unambiguous homozygous sequence. Therefore, although the prevalence of ambiguous allele combinations is high, if the resolution of these ambiguities is clinically warranted, methods exist to compensate for this problem.

Journal Article↗

PubMed2004

Transient spleen enlargement in peripheral blood progenitor cell donors given G-CSF.

The administration of granulocyte colony-stimulating factor (G-CSF) to peripheral blood progenitor cell (PBPC) donors causes spleen length to increase, but the duration of enlargement is not known. Eighteen healthy subjects were given 10 microg/kg of G-CSF for 5 days and a PBSC concentrate was collected by apheresis. Ultrasound scans were used to assess craniocaudal spleen length before and after G-CSF administration. Mean spleen length increased from a baseline length of 10.7 +/- 1.3 cm to 12.1 +/- 1.2 cm on the apheresis day (p < 0.001). Ten days after apheresis, spleen length fell to 10.5 +/- 1.2 cm and did not differ from baseline levels (p = 0.57), but in 3 subjects remained 0.5 cm greater than baseline length. Increases in spleen length in PBPC donors are transient and reversible.

Journal Article↗

PubMed2004

CD177: A member of the Ly-6 gene superfamily involved with neutrophil proliferation and polycythemia vera.

Genes in the Leukocyte Antigen 6 (Ly-6) superfamily encode glycosyl-phosphatidylinositol (GPI) anchored glycoproteins (gp) with conserved domains of 70 to 100 amino acids and 8 to 10 cysteine residues. Murine Ly-6 genes encode important lymphocyte and hematopoietic stem cell antigens. Recently, a new member of the human Ly-6 gene superfamily has been described, CD177. CD177 is polymorphic and has at least two alleles, PRV-1 and NB1. CD177 was first described as PRV-1, a gene that is overexpressed in neutrophils from approximately 95% of patients with polycythemia vera and from about half of patients with essential thrombocythemia. CD177 encodes NB1 gp, a 58-64 kD GPI gp that is expressed by neutrophils and neutrophil precursors. NB1 gp carries Human Neutrophil Antigen (HNA)-2a. Investigators working to identify the gene encoding NB1 gp called the CD177 allele they described NB1. NB1 gp is unusual in that neutrophils from some healthy people lack the NB1 gp completely and in most people NB1 gp is expressed by a subpopulation of neutrophils. The function of NB1 gp and the role of CD177 in the pathogenesis and clinical course of polycythemia vera and essential thrombocythemia are not yet known. However, measuring neutrophil CD177 mRNA levels has become an important marker for diagnosing the myeloproliferative disorders polycythemia vera and essential thrombocythemia.

Journal Article↗