Manual of Molecular and Clinical Laboratory Immunology

THE authoritative guide for clinical laboratory immunology

For over 40 years the Manual of Molecular and Clinical Laboratory Immunology has served as the premier guide for the clinical immunology laboratory. From basic serology testing to the present wide range of molecular analyses, the Manual has reflected the exponential growth in the field of immunology over the past decades. This eighth edition reflects the latest advances and developments in the diagnosis and treatment of patients with infectious and immune-mediated disorders.

Written to guide the laboratory director, the Manual will also appeal to other laboratory scientists, especially those working in clinical immunology laboratories, and pathologists. It is also a useful reference for physicians, mid-level providers, medical students, and allied health students with an interest in the role that immunology plays in the clinical laboratory.

Editorial Board xi

Contributors xiii

Foreword: How it Began xxiii

Preface xxv

Author and Editor Conflicts of Interest xxvii

Section A General Methods 1

Volume Editor: Robert G. Hamilton

Section Editor: Thomas A. Fleisher

1 Introduction 3
Thomas A. Fleisher

2 Molecular Methods for Diagnosis of Genetic Diseases Involving the Immune System 5
Amy P. Hsu

3 The Human Microbiome and Clinical Immunology 19
Frederic D. Bushman

4 Protein Analysis in the Clinical Immunology Laboratory 26
Roshini Sarah Abraham and David R. Barnidge

Section B Immunoglobulin Methods =/ 47

Volume Editor: Robert G. Hamilton

Section Editor: David F. Keren

5 Introduction 49
David F. Keren

6 Immunoglobulin Genes 51
Thomas J. Kipps, Emanuela M. Ghia, and Laura Z. Rassenti

7 Immunoglobulin Quantification and Viscosity Measurement 65
Jeffrey S. Warren

8 Clinical Indications and Applications of Serum and Urine Protein Electrophoresis 74
David F. Keren and Richard L. Humphrey

9 Immunochemical Characterization of Immunoglobulins in Serum, Urine, and Cerebrospinal Fluid 89
Elizabeth Sykes and Yvonne Posey

10 Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins 101
Peter D. Gorevic and Dennis Galanakis

11 Strategy for Detecting and Following Monoclonal Gammopathies 112
Jerry A. Katzmann and David F. Keren

Section C Complement 125

Volume Editor: Robert G. Hamilton

Section Editor: Patricia C. Giclas

12 Introduction 127
Patricia C. Giclas

13 The Classical Pathway of Complement 129
Patricia C. Giclas

14 Analysis of Activity of Mannan-Binding Lectin, an Initiator of the Lectin Pathway of the Complement System 133
Steffen Thiel

15 The Nature of the Diseases That Arise from Improper Regulation of the Alternative Pathway of Complement 138
Richard J. H. Smith

Section D Flow Cytometry 145

Volume Editor: John L. Schmitz

Section Editor: Maurice R. G. O’gorman

16 Introduction 147
Maurice R. G. O’gorman

17 Polychromatic Flow Cytometry 149
Angélique Biancotto and J. Philip Mccoy, Jr.

18 High-Sensitivity Detection of Red and White Blood Cells in Paroxysmal Nocturnal Hemoglobinuria by Multiparameter Flow Cytometry 168
Andrea Illingworth, Michael Keeney, and D. Robert Sutherland

19 Standardized Flow Cytometry Assays for Enumerating CD34+ Hematopoietic Stem Cells 182
D. Robert Sutherland and Michael Keeney

20 Functional Flow Cytometry-Based Assays of Myeloid and Lymphoid Functions for the Diagnostic Screening of Primary Immunodeficiency Diseases 199
Maurice R. G. O’gorman

21 Acute Lymphoblastic Leukemia/Lymphoma: Diagnosis and Minimal Residual Disease Detection by Flow Cytometric Immunophenotyping 207
Joseph A. Digiuseppe

22 Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry 217
Brent Wood and Lori Soma

23 Chronic Lymphocytic Leukemia, the Prototypic Chronic Leukemia for Flow Cytometric Analysis 226
Heba Degheidy, Dalia A. A. Salem, Constance M. Yuan, and Maryalice Stetler-Stevenson

24 Plasma Cell Disorders 235
Juan Flores-Montero, Luzalba Sanoja, José Juan Pérez, Fanny Pojero, Noemí Puig, María Belén Vidriales, and Alberto Orfao

25 Future Cytometric Technologies and Applications 251
Holden T. Maecker

Section E Functional Cellular Assays 259

Volume Editor: Barbara Detrick

Section Editor: Steven D. Douglas

26 Introduction 261
Steven D. Douglas

27 Cryopreservation of Peripheral Blood Mononuclear Cells 263
Adriana Weinberg

28 Lymphocyte Activation 269
Roshini Sarah Abraham

29 Functional Assays for B Cells and Antibodies 280
Moon H. Nahm and Robert L. Burton

30 Methods for Detection of Antigen-Specific T Cells by Enzyme-Linked Immunospot Assay (ELISPOT) 290
Barbara L. Shacklett and Douglas F. Nixon

31 Regulatory T Cell (Treg) Assays: Repertoire, Functions, and Clinical Importance of Human Treg 296
Theresa L. Whiteside

32 Measurement of NK Cell Phenotype and Activity in Humans 300
Samuel C. C. Chiang and Yenan T. Bryceson

33 Functional Assays for the Diagnosis of Chronic Granulomatous Disease 310
Debra Long Priel and Douglas B. Kuhns

Section F Cytokines and Chemokines 321

Volume Editor: Barbara Detrick

Section Editor: John J. Hooks

34 Introduction 323
John J. Hooks

35 Multiplex Cytokine Assays 324
Elizabeth R. Duffy and Daniel G. Remick

36 Cytokine Measurement by Flow Cytometry 338
Holden T. Maecker

37 Chemokine and Chemokine Receptor Analysis 343
Sabina A. Islam, Benjamin D. Medoff, and Andrew D. Luster

38 Cytokines: Diagnostic and Clinical Applications 357
Priyanka Vashisht and Timothy B. Niewold

39 Detection of Anticytokine Autoantibodies and Clinical Applications 365
S Arah K. Browne

Section G Immunohistology and Immunopathology 373

Volume Editor: Robert G. Hamilton

Section Editor: R. Neal Smith

40 Introduction 375
Robert G. Hamilton

41 Immunofluorescence Methods in the Diagnosis of Renal and Cardiac Diseases 376
A. Bernard Collins, James R. Stone, and R. Neal Smith

42 Western Blot Analysis for the Detection of Anti-Glomerular Basement Membrane Antibodies and Anti-Phospholipase A2 Receptor Antibodies 385
A. Bernard Collins and R. Neal Smith

Section H Infectious Diseases Caused by Bacteria, Mycoplasmas, Chlamydiae, and Rickettsiae 391

Volume Editor: John L. Schmitz

Section Editor: Christine M. Litwin

43 Introduction 393
Christine M. Litwin

44 Diagnostic Methods for Group A Streptococcal Infections 394
Christine M. Litwin, Sheldon E. Litwin, and Harry R. Hill

45 Diagnosis of Helicobacter pylori Infection andAssessment of Eradication 404
Bruce E. Dunn and Suhas H. Phadnis

46 Laboratory Diagnosis of Syphilis 412
John L. Schmitz

47 Lyme Disease, Relapsing Fever, and Leptospirosis 419
Guiqing Wang and Maria E. Aguero-Rosenfeld

48 Immunological Tests in Tuberculosis 433
Christine M. Litwin

49 Mycoplasma: Immunologic and Molecular Diagnostic Methods 444
Ken B. Waites, Mary B. Brown, and Jerry W. Simecka

50 Chlamydia and Chlamydophila Infections 453
Rosemary She

51 The Rickettsiaceae, Anaplasmataceae, and Coxiellaceae 461
Lucas S. Blanton and David H. Walker

52 The Bartonellaceae, Brucellaceae, and Francisellaceae 473
Christine M. Litwin, Burt Anderson, Renee Tsolis, and Amy Rasley

Section I Mycotic and Parasitic Diseases 483

Volume Editor: Robert G. Hamilton

Section Editor: Thomas B. Nutman

53 Introduction 485
Thomas B. Nutman

54 Immunological and Molecular Approaches for the Diagnosis of Parasitic Infections 486
Patricia P. Wilkins and Thomas B. Nutman

55 Serological and Molecular Diagnosis of Fungal Infections 503
Mark D. Lindsley

Section J Viral Diseases 535

Volume Editor: John L. Schmitz

Section Editors: Richard L. Hodinka and John L. Schmitz

56 Introduction 537
John L. Schmitz

57 Immunologic and Molecular Methods for Viral Diagnosis 538
Marie Louise Landry and Yi-Wei Tang

58 Herpes Simplex Virus 550
D. Scott Schmid

59 Varicella-Zoster Virus 556
D. Scott Schmid

60 Epstein-Barr Virus and Cytomegalovirus 563
Henry H. Balfour, Jr., Kristin A. Hogquist, and Priya S. Verghese

61 Human Herpesviruses 6, 7, and 8 578
Richard L. Hodinka

62 Parvovirus B19 591
Stanley J. Naides

63 Respiratory Viruses 598
David J. Speicher, Mohsin Ali, and Marek Smieja

64 Measles, Mumps, and Rubella Viruses 610
Diane S. Leland and Ryan F. Relich

65 Viral Hepatitis 620
Hubert G. M. Niesters, Annelies Riezebos-Brilman, and Coretta C. Van Leer-Buter

66 Viral Agents of Gastroenteritis 639
Gabriel I. Parra and Kim Y. Green

67 Arboviruses 648
Robert S. Lanciotti and John T. Roehrig

68 Diagnosis of Hantavirus Infections 658
William Marciel De Souza and Luiz Tadeu Moraes Figuereido

69 Rabies Virus 665
D. Craig Hooper

70 Human T-Cell Lymphotropic Virus Types 1 and 2 674
Breanna Caruso, Raya Massoud, and Steven Jacobson

71 Diagnosis of Prion Diseases 682
Richard Rubenstein, Robert B. Petersen, and Thomas Wisniewski

72 Principles and Procedures of Human Immunodeficiency Virus Diagnosis 696
Kelly A. Curtis, Jeffrey A. Johnson, and S. Michele Owen

Section K Immunodeficiency Diseases 711

Volume Editor: Barbara Detrick

Section Editors: Kathleen E. Sullivan and Howard M. Lederman

73 The Primary Immunodeficiency Diseases 713
Howard M. Lederman

74 Severe Combined Immune Deficiency: Newborn Screening 715
James W. Verbsky and John M. Routes

75 Combined Immunodeficiencies 721
Christine Seroogy and Melissa Elder

76 Antibody Deficiencies 737
Kimberly C. Gilmour, Anita Chandra, and D. S. Kumararatne

77 Hereditary and Acquired Complement Deficiencies 749
Patricia C. Giclas

78 Neutropenia and Neutrophil Defects 765
Steven M. Holland

79 Evaluation of Natural Killer (NK) Cell Defects 774
Kimberly Risma and Rebecca Marsh

Section L Allergic Diseases 781

Volume Editor: Robert G. Hamilton

Section Editor: Pamela A. Guerrerio

80 Introduction 783
Pamela A. Guerrerio

81 Quantitation and Standardization of Allergens 784
Ronald L. Rabin, Lynnsey Renn, and Jay E. Slater

82 Immunological Methods in the Diagnostic Allergy Clinical and Research Laboratory 795
Robert G. Hamilton

83 Assay Methods for Measurement of Mediators and Markers of Allergic Inflammation 801
John T. Schroeder, R. Stokes Peebles, Jr., and Pamela A. Guerrerio

84 Tests for Immunological Reactions to Foods 815
Carah B. Santos, David M. Fleischer, and Robert A. Wood

85 Diagnosis of Rare Eosinophilic and Mast Cell Disorders 825
Cem Akin, Calman Prussin, and Amy D. Klion

Section M Systemic Autoimmune Diseases 839

Volume Editor: Barbara Detrick

Section Editor: Westley H. Reeves

86 Introduction 841
Westley H. Reeves

87 Antinuclear Antibody Tests 843
Alessandra Dellavance, Wilson De Melo Cruvinel, Paulo Luiz Carvalho Francescantonio, and Luis Eduardo Coelho Andrade

88 Detection of Autoantibodies by Enzyme-Linked Immunosorbent Assay and Bead Assays 859
Edward K. L. Chan, Rufus W. Burlingame, and Marvin J. Fritzler

89 Immunodiagnosis and Laboratory Assessment of Systemic Lupus Erythematosus 868
Westley Reeves, Shuhong Han, John Massini, and Yi Li

90 Immunodiagnosis of Autoimmune Myopathies 878
Minoru Satoh, Angela Ceribelli, Michito Hirakata, and Edward K. L. Chan

91 Immunodiagnosis of Scleroderma 888
Masataka Kuwana

92 Antibody and Biomarker Testing in Rheumatoid Arthritis 897
Ann Duskin Chauffe and Michael Raymond Bubb

93 Antiphospholipid Antibody Syndrome: Clinical Manifestations and Laboratory Diagnosis 905
Martina Murphy and Neil Harris

94 Antineutrophil Cytoplasmic Antibodies (ANCA) and Strategies for Diagnosing ANCA-Associated Vasculitides 909
R. W. Burlingame, C. E. Buchner, J. G. Hanly, and N. M. Walsh

95 IgG4-Related Disease: Diagnostic Testing by Serology, Flow Cytometry, and Immunohistopathology 917
John H. Stone

96 Future Perspectives for Rheumatoid Arthritis and Other Autoimmune Diseases 922
Jeremy Sokolove

Section N Organ-localized Autoimmune Diseases 927

Volume Editor: John L. Schmitz

Section Editors: C. Lynne Burek and Patrizio Caturegli

97 Introduction 929
C. Lynne Burek

98 Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis 930
C. Lynne Burek, N. R. Rose, Giuseppe Barbesino, Jian Wang, Andrea K. Steck, George S. Eisenbarth, Liping Yu, Ludovica De Vincentiis, Adriana Ricciuti, Alessandra De Remigis, and Patrizio Caturegli

99 Myasthenia Gravis 954
Arnold I. Levinson and Robert P. Lisak

100 Autoantibodies to Glycolipids in Peripheral Neuropathy 961
Hugh J. Willison

101 Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis 966
Patrick S. C. Leung, Michael P. Manns, Ross L. Coppel, and M. Eric Gershwin

102 Cardiovascular Diseases 975
Cheryl L. Maier, C. Lynne Burek, Noel R. Rose, and Aftab A. Ansari

103 Celiac Disease and Inflammatory Bowel Disease 983
Melissa R. Snyder

104 Autoantibodies Directed against Erythrocytes in Autoimmune Hemolytic Anemia 990
R. Sue Shirey and Karen E. King

105 Immune Thrombocytopenia 995
Thomas S. Kickler

106 Monitoring Autoimmune Reactivity within the Retina 998
John J. Hooks, Chi-Chao Chan, H. Nida Sen, Robert Nussenblatt, and Barbara Detrick

Section O Cancer 1005

Volume Editor: Robert G. Hamilton

Section Editors: Daniel Chan and Lori J. Sokoll

107 Introduction 1007
Robert G. Hamilton

108 Immunoassay-Based Tumor Marker Measurement: Assays, Applications, and Algorithms 1008
Elizabeth A. Godbey, Lori J. Sokoll, and Alex J. Rai

109 Malignancies of the Immune System: Use of Immunologic and Molecular Tumor Markers in Classification and Diagnostics 1015
Elaine S. Jaffe and Mark Raffeld

110 Monitoring of Immunologic Therapies 1036
Theresa L. Whiteside

111 Circulating Tumor Cells as an Analytical Tool in the Management of Patients with Cancer 1051
Daniel C. Danila, Howard I. Scher, and Martin Fleisher

Section P Transplantation Immunology 1063

Volume Editor: Barbara Detrick

Section Editors: Elaine F. Reed and Qiuheng Jennifer Zhang

112 Histocompatibility and Immunogenetics Testing in the 21st Century 1065
Qiuheng Jennifer Zhang and Elaine F. Reed

113 Molecular Methods for Human Leukocyte Antigen Typing: Current Practices and Future Directions 1069
Mark Kunkel, Jamie Duke, Deborah Ferriola, Curt Lind, and Dimitri Monos

114 Evaluation of the Humoral Response in Transplantation 1091
Paul Sikorski, Renato Vega, Donna P. Lucas, and Andrea A. Zachary

115 Non-Human Leukocyte Antigen Antibodies in Organ Transplantation 1103
Annette M. Jackson and Bethany L. Dale

116 Evaluation of the Cellular Immune Response in Transplantation 1108
Diana Metes, Nancy L. Reinsmoen, and Adriana Zeevi

117 Complement in Transplant Rejection 1123
Carmela D. Tan, E. Rene Rodriguez, and William M. Baldwin Iii

118 Molecular Characterization of Rejection in Solid Organ Transplantation 1132
Darshana Dadhania, Tara K. Sigdel, Thangamani Muthukumar, Choli Hartono, Minnie M. Sarwal, and Manikkam Suthanthiran

119 Killer Cell Immunoglobulin-Like Receptors in Clinical Transplantation 1150
Raja Rajalingam, Sarah Cooley, and Jeroen Van Bergen

120 Chimerism Testing 1161
Lee Ann Baxter-Lowe

Section Q Laboratory Management 1169

Volume Editor: Robert G. Hamilton

Section Editor: Ronald J. Harbeck

121 Clinical Immunology Laboratory Accreditation, Licensure, and Credentials 1171
Linda Cook and Ronald J. Harbeck

122 Validation and Quality Control: General Principles and Application to the Clinical Immunology Laboratory 1180
Vijaya Knight and Terri Lebo

Author Index 1193

Subject Index 1195

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