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Immunology and Flow Cytometry

3D chart The Immunology and Flow Cytometry Laboratories are responsible for laboratory testing (approximately 150 analytes) and clinical consultation in several broad areas of medicine, including diagnosis of myelo- and lymphoproliferative disease, immunodeficiencies, autoimmune disease, tumor biology, hematopoietic stem cell transplantation monitoring, and infectious disease serology and molecular diagnostics. Much work is carried out together with the Molecular Diagnostics and the Special Coagulation Laboratory subdivisions to provide seamless consultation and diagnostics for various clinical scenarios. New work in the area of infectious disease diagnostics is carried out in collaboration with the Microbiology and Virology Laboratories. The laboratories function as important reference laboratory facilites for several major areas of emphasis, including:
Myeloproliferative/Lymphoproliferative Disease Diagnostics
Standard consultative diagnostics in this area usually involve coordinated "reflex" analysis of a blood, marrow, fluid or other specimen by clinical review, morphology, specialhistochemistry stains, flow cytometric surface marker and intracellular antigen analysis, DNA ploidy analysis, serum protein analysis and molecular evaluation. A major effort is made to carry out these analyses in as parsimonious a fashion as possible while providing comprehensive, clinically useful information so as to maximize both the highest quality patient care and simultaneously maximize cost-effectiveness for the patient. Hematopoietic stem cell culture assays are available to help evaluate patients with suspected polycythemia vera and other myeloproliferative syndromes. The faculty have been leaders in these areas for many years. See, for example, department publications:

  1. Howe JG, Crouch J, Cooper D, Smith BR. 2004. Real-Time Quantitative RT-PCR of Cyclin D1 mRNA for Mantle Cell Lymphoma Diagnosis in Blood, Marrow and Tissue Specimens. Clin Chem 50: 80-7. (PubMed)
  2. Wang S. Ernst LM. Smith BR. Tallini G. Howe JG. Crouch J. Cooper DL. 2003. Systemic Tropheryma whippleii infection associated with monoclonal B-cell proliferation: a Helicobacter pylori-type pathogenesis? Arch Pathol Lab Med 127:1619-22. (PubMed)
  3. Hui P, Howe JG, Crouch J, Nimmakayalu M, Qumsiyeh MB, Tallinni G, Flynn S, Smith BR. 2003. Real-time quantitative RT-PCR of Cyclin D1 mRNA expression in mantle cell lymphomas: comparison with FISH and immunohistochemistry. Leukemia & Lymphoma 44: 1385-94. (PubMed)
  4. Wang C, Smith BR, Ault KA, Rinder HM. 2002. A new peripheral blood measure of stress thrombopoiesis predicts imminent platelet recovery. Transfusion 42: 368-74.
  5. Debelak J, Shlomchik MJ, Snyder EL, Cooper D, Seropian S, McGuirk J, Smith B, Krause DS. 2000. Isolation and FACS analysis of T cell depleted CD34+ peripheral blood stem cells. Transfusion 40: 1475-81.
  6. McGuirk JP, Seropian S, Howe, G, Smith B, Stoddart L, and Cooper DL. 1999. Use of rituximab and irradiated donor-derived lymphocytes to control Epstein-Barr virus-associated lymphoproliferation in patients undergoing related haplo-identical stem cell transplantation. Bone Marrow Transplant 24(11): 1253-1258.
  7. Crotty PL, Smith BR, Tallini G. 1998. Morphologic, immunophenotypic and molecular evolution of bone marrow involvement in non-Hodgkin's lymphoma. Diag Mol Path 7(2):90-95.
  8. Smith BR. 1997. Hematopoietic Stem Cell Transplantation. In: DeVita VT, Hellman S, Rosenberg SA. "Cancer: Principles and Practice of Oncology, 5th edition" (J.B. Lippincott Co., Philadelphia, PA) pp 2621-2638.
  9. Leitenberg D, Gilliand DG, Eisen R, Rinder H, Goldstein J, Stys P, Smith BR. 1995. Natural Killer Cell Lymphoproliferative Disease Associated with Chronic Demyelinating Neuropathy. Am J Med 99:99-102.
  10. Antin JH, Smith BR. 1995. Bone Marrow Transplantation. In: Handin RI, Lux SE, Stossel TP "Blood: Principles and Practice of Hematology" (J.B. Lippincott Co, Philadelphia, PA), pp. 2055-2103.
  11. Berliner N, Smith BR. 1994. The Pathobiology of Lymphoproliferative Disease. In: Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ (eds): "Hematology: Basic Principles and Practice, 2nd Edition" (New York: Churchill Livingstone), pp. 1193-1213.
  12. Leitenberg D, Rappeport JM, Smith BR. 1994. Precursor B Cell Bone Marrow Reconstitution Following Marrow Transplant. Am J Clin Pathol 102:231-236.
  13. Smith BR. 1993. Qualitative versus Quantitative Immunophenotyping. Annals of the New York Academy of Sciences 677:152-154.
  14. Smith BR. 1993. Integrating Flow Cytometry into the Hematology Laboratory: A Curmudgeon's View. Annals of the New York Academy of Sciences 677:326-333.
  15. Mitus AJ, Stein RS, Rappeport JM, Antin JH, Weinstein HJ, Alper CA, Smith BR. 1989. Monoclonal and Oligoclonal Gammopathy After Bone Marrow Transplantation. Blood 74:2764-2768.
  16. Antin JH, Bierer BE, Smith BR, Ferrara J, Guinan EC, Sieff C, Macklis RM, Tarbell NJ, Lynch E, Reichert T, Blythman H, Bouloux C, Rappeport JM, Burakoff SJ, Weinstein HJ. 1991. Selective Depletion of Bone Marrow T-Lymphocytes with Anti-CD5 Monoclonal Antibodies: Effective Prophylaxis for Graft-versus-Host Disease in Patients with Hematologic Malignancies. Blood 78:2139-2149.
Several of the faculty are also recognized nationally for their therapeutic contributions in hematologic malignancy as well as their diagnostic contributions. This "multiple hat" capacity significantly enhances consultative utility of the diagnostic tests performed.
   

Platelet Disorder Diagnostics

The laboratory has been a leader in the area of new techniques to evaluate quantitative and qualitative platelet disorders, including reticulated platelet analysis to non-invasively assess platelet kinetics, antigen-specific anti-platelet antibody testing (e.g., anti-gpIIb/IIIa, anti-gpIb, anti-gpIV), and new approaches to studying platelet function. See, for example, department publications:
  1. Esposito C, Popescu W, Rinder HM, Schwartz J, Smith BR, Rinder CS. 2003. Increased leukocyte-platelet adhesion in patients with graft occlusion after peripheral vascular surgery. Thrombosis Haemostasis 90: 1128-34. (PubMed)
  2. H.M. Rinder, E.L. Snyder, J.B. Tracey, D. Dincecco, C. Wang, L. Baril, C.S. Rinder, and B.R. Smith. 2003. Reversibility of severe metabolic stress in stored platelets following in vitro plasma rescue or in vivo transfusion: restoration of secretory function and maintenance of platelet survival. Transfusion 43: 1230-7. (PubMed)
  3. Rinder HM, Smith BR. 2003. In Vitro Evaluation of Stored Platelets: Is there hope for predicting post-transfusion platelet survival and function? Transfusion 43:2-6. (PubMed)
  4. Wang C, Smith BR, Ault KA, Rinder HM. 2002. A new peripheral blood measure of stress thrombopoiesis predicts imminent platelet recovery following chemotherapy. Transfusion 42: 368-74. (PubMed)
  5. Griffin MJ, Rinder HM, Smith BR, Tracey JB, Kriz N, Rinder CS. 2001. Effects of Heparin, Protamine and Heparin-Protamine Reversal on Platelet Function under Conditions of Arterial Shear Stress. Anesthesia & Analgesia 93:20-7
  6. Mathew JP, Rinder CS, Rinder HM, Howe JG, Crouch J, Newman MF, Fontes M, Phillips-Bute B, Smith BR and McSPI. 2001. Platelet GP IIIa PIA2 polymorphism enhances the risk of neurocognitive decline after cardiopulmonary bypass. Ann Thorac Surg 71: 663-6.
  7. Smith BR. 1997. Interactions of Platelets and Endothelial Cells with Erythrocytes and Leukocytes in TTP. Sem Hematol 34:90-97.
  8. Rinder HM, Schuster, JE, Rinder CS, Wang C, Schweidler HJ, Smith BR. 1998. Correlation of Thrombosis with Increased Platelet Turnover in Thrombocytosis. Blood 91:1288-1294.
  9. Rinder HM, Bonan JL, Anandan S, Rinder CS, Rodrigues PA, Smith BR. 1994. Non-invasive Measurement of Platelet Kinetics in Normal and Hypertensive Pregnancies. Am J Obs Gynecol 170:117-122.
  10. Rinder HM, Munz U, Ault KA, Bonan JL, Smith BR. 1993. Reticulated Platelets in the Evaluation of Thrombopoietic Disorders. Arch Pathol Lab Med 117:606-610
Testing available includes molecular platelet allotyping as well as the areas outlined above.
   
Immunodeficiency Evaluation
The laboratory performs both quantitative assessment of lymphocytes as well as functional studies (e.g., proliferation assays). Recent areas of research and development interest have centered on understanding the utility of immune evaluation in transplantation settings as well as in several other clinical settings such as extracorporeal circulation. See, for example, department publications:
  1. Zieske A, Smith BR. 2004. Basic Biology of Hematopoietic Progenitor Cell Transplantation. In: "Hematopoietic Progenitor Cells: A Primer for Medical Professionals (Snyder EL, Haley NR, eds), pp (in press), AABB Press.
  2. Smith BR, Rinder CS, Rinder HM. 2002. Interaction of Blood and Artificial Surfaces. In: Loscalzo J, Schafer AI (eds) "Thrombosis and Hemorrhage, 3rd Edition" (Lippincott Williams & Wilkins, Philadelphia, PA) (pp 865-885).
  3. Rinder CS, Mathew JP, Rinder HM, Tracey JS, Davis E, Smith BR. 1997. Immunosuppression and Immune Stimulation During Cardiopulmonary Bypass: Effects of Aging and Gender. J Lab Clin Med 129:592-602.
  4. Berliner N, Smith BR. 1994. The Pathobiology of Lymphoproliferative Disease. In: Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ (eds): "Hematology: Basic Principles and Practice, 2nd Edition" (New York: Churchill Livingstone), pp. 1193-1213.
  5. Howe G, Smith BR, Talini G. 1997. Epstein-Barr Virus Suspension Cell Assay Using In Situ Hybridization of Flow Cytometry. Cytometry 29:50-57.
   
Tumor Biology
In addition to performing standard tumor marker evaluation, the laboratory has an ongoing interest in determining the clinical utility (or lack thereof) of following "minimal residual disease" through both flow cytometric and through molecular techniques. An area of particular interest currently in development is that of combining flow cytometric, molecular diagnostic, and image analysis technology to provide clinically useful information. See, for example, department publication:
  1. Smith BR. 1997. Hematopoietic Stem Cell Transplantation. In: DeVita VT, Hellman S, Rosenberg SA. "Cancer: Principles and Practice of Oncology, 5th edition" (J.B. Lippincott Co., Philadelphia, PA) pp 2621-2638.
  2. Mitus AJ, Stein RS, Rappeport JM, Antin JH, Weinstein HJ, Alper CA, Smith BR. 1989. Monoclonal and Oligoclonal Gammopathy After Bone Marrow Transplantation. Blood 74:2764-2768.
   
Autoimmune Disease Testing/Allergy Testing
The laboratory provides reference diagnostics for some unusual "food allergy" scenarios in pediatric patients and autoimmune hematologic disease (e.g., ITP). Complete cryoglobulin evaluation is an area of particular interest. The laboratory also concentrates on providing maximally cost-effective testing for rheumatologic and other autoimmune conditions.
   
Infectious Disease Testing

Most infectious disease testing is carried out through the Microbiology and Virology Laboratories. However, certain routine and reference serological testing (e.g., mycoplasma and syphillis IgM serologies) are performed in the Immunology Laboratory. The laboratory also helps support the work of the Microbiology and Molecular Diagnostics laboratories in providing rapid identification of unusual pathogens that are difficult to characterize by standard biochemical means through the technique of using 16S ribosomal nucleic acid amplification and sequencing.
   

Laboratory Contacts
Laboratory Phone Numbers:
Immunology 203-688-2440
Flow Cytometry 203-688-2437
FAX Number 203-688-4111

Brian R. Smith, MD
Director, Immunology and Flow Cytometry Laboratories
Vice Chair, Dept of Laboratory Medicine
Professor of Laboratory Medicine, Internal Medicine and Pediatrics

Henry M. Rinder, MD
Associate Director, Hematology Laboratory
Associate Professor of Laboratory Medicine and Internal Medicine

Michael Ripps, MD, PhD
Associate Research Scientist

Josephine Annunziata
Chief Technologist

Ursula Munz
Flow Cytometry Specialist

 

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Page last revised: April 30, 2007