Principles and applications of flow cytometry and cell sorting in companion animal medicine.

Flow cytometry measures multiple characteristic of single cells using light scatter properties and fluorescence properties of fluorescent probes with specificity to cellular constituents. The use of flow cytometry in the veterinary clinical laboratory has become more routine in veterinary diagnostic laboratories and institutions (http://www.vet.k-state.edu/depts/dmp/service/immunology/index.htm), and reference laboratories. The most common applications in small animal medicine includes quantitation of erythrocytes and leukocytes in automated hematology instruments, detection of antibodies to erythrocytes and platelets in cases of immune-mediated diseases, immunophenotyping of leukocytes and lymphocytes in immunodeficiency syndromes, or leukemias and lymphomas. DNA content analysis to identify aneuploidy or replicating cells in tumor preparations has not gained routine acceptance because of the variability of prognostic results. Other applications including cell sorting and multiplexing using microspheres are potential assays of the future once they become validated and the instrumentation footprint becomes more and more compact, less expensive, and easier to use.

[1]  D. Weiss.  Flow Cytometric and Immunophenotypic Evaluation of Acute Lymphocytic Leukemia in Dog Bone Marrow , 2001 .

[2]  Derek Davies,et al.  Cell Sorting by Flow Cytometry , 2007 .

[3]  J. Modiano,et al.  Use of the Cell-Dyn 3500 to predict leukemic cell lineage in peripheral blood of dogs and cats. , 2002, Veterinary clinical pathology.

[4]  D. Danilenko,et al.  Monoclonal antibodies specific for canine CD4 and CD8 define functional T-lymphocyte subsets and high-density expression of CD4 by canine neutrophils. , 1992, Tissue antigens.

[5]  M. Dark,et al.  SCID in Jack Russell Terriers: A New Animal Model of DNA-PKcs Deficiency1 , 2001, The Journal of Immunology.

[6]  D. McCarthy,et al.  Fluorochromes and Fluorescence , 2007 .

[7]  M. Boudreaux,et al.  Clinical, Biochemical, and Molecular Aspects of Glanzmann's Thrombasthenia in Humans and Dogs , 2001, Veterinary pathology.

[8]  J. Tarrant.  The role of flow cytometry in companion animal diagnostic medicine. , 2005, Veterinary journal.

[9]  D. Rigal,et al.  Abnormalities of lymphocyte subsets in canine systemic lupus erythematosus. , 1995, Autoimmunity.

[10]  M. Miller,et al.  Classification of Canine Malignant Lymphomas According to the World Health Organization Criteria , 2011, Veterinary pathology.

[11]  H. Tvedten,et al.  Canine automated differential leukocyte count: study using a hematology analyzer system. , 1994, Veterinary clinical pathology.

[12]  K. Meyers,et al.  Effect of anticoagulant and blood storage time on platelet-bound antibody concentrations in clinically normal dogs. , 1994, American journal of veterinary research.

[13]  Paul R. Avery,et al.  Canine lymphoproliferative disease characterized by lymphocytosis: immunophenotypic markers of prognosis. , 2008, Journal of veterinary internal medicine.

[14]  M. Wilkerson,et al.  Alterations in normal canine platelets during storage in EDTA anticoagulated blood. , 2001, Veterinary clinical pathology.

[15]  A. Moritz,et al.  Automated flow cytometric cell count and differentiation of canine cerebrospinal fluid cells using the ADVIA 2120. , 2008, Veterinary clinical pathology.

[16]  J. Meinkoth,et al.  Platelet size, platelet surface-associated IgG, and reticulated platelets in dogs with immune-mediated thrombocytopenia. , 2001, Veterinary clinical pathology.

[17]  V. Fert,et al.  Simultaneous Detection of Multiplex-Amplified Human Immunodeficiency Virus Type 1 RNA, Hepatitis C Virus RNA, and Hepatitis B Virus DNA Using a Flow Cytometer Microsphere-Based Hybridization Assay , 2000, Journal of Clinical Microbiology.

[18]  M. E. Gorman,et al.  Comparison between manual and automated total nucleated cell counts using the ADVIA 120 for pleural and peritoneal fluid samples from dogs, cats, horses, and alpacas. , 2009, Veterinary clinical pathology.

[19]  W. Tompkins,et al.  Lentivirus-induced immune dysregulation. , 2008, Veterinary immunology and immunopathology.

[20]  Roger D. Smith,et al.  Quantitation of reticulated platelets in healthy dogs and in nonthrombocytopenic dogs with clinical disease. , 2002, Veterinary clinical pathology.

[21]  W. Davis,et al.  Peripheral blood and synovial fluid mononuclear cell phenotypes in lentivirus induced arthritis. , 1995, The Journal of rheumatology.

[22]  C. Cornelisse,et al.  DNA ploidy and cell kinetic characteristics in canine non-Hodgkin's lymphoma. , 1993, Experimental hematology.

[23]  J. Modiano,et al.  Diagnosis of Canine Lymphoid Neoplasia Using Clonal Rearrangements of Antigen Receptor Genes , 2003, Veterinary pathology.

[24]  I. Nolte,et al.  Flow cytometry and its application in small animal oncology. , 2002, Methods in cell science : an official journal of the Society for In Vitro Biology.

[25]  M. B. Mays,et al.  Characteristics of Canine Melanomas and Comparison of Histology and DNA Ploidy to Their Biologic Behavior , 1990, Veterinary pathology.

[26]  Y. Shoenfeld,et al.  Multiplexed AtheNA multi-lyte immunoassay for ANA screening in autoimmune diseases , 2005, Autoimmunity.

[27]  Schalm Ow,et al.  Schalm's Veterinary Hematology , 1986 .

[28]  Bruce Greig,et al.  2006 Bethesda International Consensus recommendations on the immunophenotypic analysis of hematolymphoid neoplasia by flow cytometry: Optimal reagents and reporting for the flow cytometric diagnosis of hematopoietic neoplasia , 2007, Cytometry. Part B, Clinical cytometry.

[29]  L. Barber,et al.  Lineage differentiation of canine lymphoma/leukemias and aberrant expression of CD molecules. , 2005, Veterinary immunology and immunopathology.

[30]  B. Hartnett,et al.  Canine X-linked severe combined immunodeficiency , 1998, Immunologic research.

[31]  W. Carlton,et al.  Flow Cytometric DNA Ploidy Analysis in Canine Transitional Cell Carcinoma of Urinary Bladders , 1994, Veterinary pathology.

[32]  M. Macey,et al.  Cytometric analysis of cell phenotype and function: Principles of flow cytometry , 2001 .

[33]  P. Moore,et al.  An immunophenotypic study of canine leukemias and preliminary assessment of clonality by polymerase chain reaction. , 1999, Veterinary immunology and immunopathology.

[34]  D. Weiss.  Evaluation of Proliferative Disorders in Canine Bone Marrow by Use of Flow Cytometric Scatter Plots and Monoclonal Antibodies , 2001, Veterinary pathology.

[35]  D. Haines,et al.  Application of a Direct Flow Cytometric Erythrocyte Immunofluorescence Assay in Dogs with Immune-Mediated Hemolytic Anemia and Comparison to the Direct Antiglobulin Test , 2001, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[36]  D. Bienzle,et al.  Flow Cytometry in Veterinary Oncology , 2011, Veterinary pathology.

[37]  Lewis Dc,et al.  Development and characterization of a flow cytometric assay for detection of platelet-bound immunoglobulin G in dogs. , 1995 .

[38]  M. Wilkerson,et al.  Anti-A isoagglutinins in two blood type B cats are IgG and IgM. , 1991, Veterinary clinical pathology.

[39]  C. Milstein,et al.  Continuous cultures of fused cells secreting antibody of predefined specificity , 1975, Nature.

[40]  C. Couto,et al.  Correlation of DNA Ploidy to Tumor Histologic Grade, Clinical Variables, and Survival in Dogs with Mast Cell Tumors , 1992, Veterinary pathology.

[41]  M. Hamilton,et al.  Use of monoclonal antibodies and flow cytometry to cluster and analyze leukocyte differentiation molecules. , 1995, Methods in molecular biology.

[42]  S. Holland,et al.  Leukocyte Adhesion Deficiency in Children and Irish Setter Dogs , 2004, Pediatric Research.

[43]  H. Brown,et al.  A hereditary bleeding disorder of dogs caused by a lack of platelet procoagulant activity. , 2002, Blood.

[44]  B. Rush,et al.  Isotype-specific antibodies in horses and dogs with immune-mediated hemolytic anemia. , 2000, Journal of veterinary internal medicine.

[45]  H. Tvedten,et al.  Automated differential leukocyte count in horses, cattle, and cats using the Technicon H-1E hematology system. , 1996, Veterinary clinical pathology.

[46]  M. Macey,et al.  Flow Cytometry: Principles and Applications , 2007 .

[47]  L. Holmberg,et al.  Prognostic Factors in Canine Mammary Tumors: A Multivariate Study of 202 Consecutive Cases , 1993, Veterinary pathology.

[48]  B. Wagner,et al.  Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses. , 2009, Veterinary immunology and immunopathology.

[49]  A. Avery.  Molecular diagnostics of hematologic malignancies. , 2009, Topics in companion animal medicine.

[50]  D. Weiss,et al.  Flow cytometric evaluation of canine bone marrow differential cell counts. , 2000, Veterinary clinical pathology.

[51]  D. Weiss,et al.  Comparison of microscopic and flow cytometric detection of platelet antibody in dogs suspected of having immune-mediated thrombocytopenia. , 1994, American journal of veterinary research.

[52]  K. Harkin,et al.  Development and evaluation of a flow cytometry microsphere assay to detect anti-histone antibody in dogs. , 2005, Veterinary immunology and immunopathology.

[53]  D. Weiss.  Evaluation of antineutrophil IgG antibodies in persistently neutropenic dogs. , 2007, Journal of veterinary internal medicine.

[54]  Paul R. Avery,et al.  Molecular methods to distinguish reactive and neoplastic lymphocyte expansions and their importance in transitional neoplastic states. , 2004, Veterinary clinical pathology.

[55]  J. McCoy,et al.  Current practices in clinical flow cytometry. A practice survey by the American Society of Clinical Pathologists. , 1999, American journal of clinical pathology.

[56]  M. Roederer,et al.  The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford. , 2002, Clinical chemistry.

[57]  A. Moritz,et al.  Evaluation of three methods for measurement of hemoglobin and calculated hemoglobin parameters with the ADVIA 2120 and ADVIA 120 in dogs, cats, and horses. , 2008, Veterinary clinical pathology.

[58]  D. Rigal,et al.  Clinical applications of flow cytometry and cell immunophenotyping to companion animals (dog and cat). , 2000, Methods in cell science : an official journal of the Society for In Vitro Biology.

[59]  D. Weiss,et al.  Evaluation of reticulated platelets in dogs , 1998, Comparative Haematology International.