| Publications by Biophoenix' Principals |
| Diagnosis of Immune Dysfunction | |
|---|---|
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| Publisher: | PJB Publications |
| Year of publication: | 1992 |
| Type of publication: | Management report |
| Publisher's reference (if any): | CBS 260 |
| Author(s): | Sreten Bogdanovic and Beata Langlands |
| Approximate page count: | 150 |
| Price when published: | £300 |
Remarks:
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DIAGNOSIS OF IMMUNE DYSFUNCTION
A report for
Clinica World Medical Device and Diagnostics News
(c) June 1992 by PJB Publications
TABLE OF CONTENTS
TABLE OF CONTENTS i
EXECUTIVE SUMMARY vii
CHAPTER 1 OVERVIEW OF IMMUNOLOGY
1.1 Overview of immune dysfunction 1
1.2 Scope of this Report 2
1.3 Exchange rates used in this Report 3
1.4 The nature of the immune system 4
1.5 Protein and cellular components
of the immune system 4
1.5.1 Immunoglobulin, complement, and HLA systems 4
1.5.1.1 Immunoglobulins 4
1.5.1.2 Complement proteins 5
1.5.1.3 HLA proteins 6
1.5.2 Cellular components of the immune system 7
1.5.2.1 Lymphocytes 7
1.5.2.2 Phagocytes 8
1.5.2.3 Mast cells, basophils, and eosinophils 9
1.5.2.4 Killer cells 10
1.6 Cell interactions and cytokines 10
1.6.1 Direct cellular interactions 11
1.6.2 Interactions mediated by cytokines 11
1.7 Immune-system mediated inflammation 12
1.8 Summary of interactions involving protein
and cellular components of the immune system 13
CHAPTER 2 ATOPIC AND RELATED DISORDERS
2.1 Terminology of allergy 15
2.2 Immunopathology of the atopic state 16
2.2.1 IgE-mediated mechanisms - general
considerations 16
2.2.2 IgE-mediated mechanisms in
parasitic infections 17
2.2.3 IgE-mediated mechanisms in an
atopic individual 18
2.3 Clinical presentations of atopy 19
2.3.1 General considerations 19
2.3.2 Atopic or allergic rhinitis (hay fever) 20
2.3.3 Atopic asthma 20
2.3.4 Atopic eczema/dermatitis 23
2.3.5 Food allergy 23
2.3.6 Urticaria (hives) and angioedema 25
2.4 IgE-mediated hypersensitivity in
non-atopic individuals 26
2.4.1 General considerations 26
2.4.2 Anaphylaxis 26
2.4.3 AIDS 27
2.5 Treatment of atopic diseases 27
2.5.1 General considerations 27
2.5.2 Prophylactic treatments 27
2.5.3 Treatment with drugs 28
2.6 Current investigations into the aetiology of
atopic and related IgE-mediated disorders 29
2.6.1 Atopic diseases 29
2.6.2 Parasitic infections 29
2.6.3 AIDS 29
2.6.4 Therapeutic potential of
B cell-tropic cytokines 30
CHAPTER 3 AUTOIMMUNE DISEASE
3.1 Introduction and terminology 31
3.2 Tolerance to autoantigens 32
3.2.1 Mechanisms of tolerance 32
3.2.2 Tolerance breakdown 32
3.2.2.1 Events which can elicit
anti-self responses 33
3.2.2.2 Mechanisms which result in chronic
stimulation of autoreactive TH cells 34
3.3 Autoimmunity and tolerance breakdown 34
3.4 Factors predisposing to autoimmune disease 35
3.4.1 Effect of age 35
3.4.2 Sex influences 35
3.4.3 Genetic factors 35
3.4.4 Associations with HLA haplotypes 36
3.5 Mechanisms of immunopathology in
autoimmune diseases 36
3.6 Organ-specific autoimmune diseases 38
3.6.1 Thyroid-specific autoimmune diseases 38
3.6.1.1 Hashimoto's thyroiditis
(autoimmune thyroiditis) 38
3.6.1.1.1 Introduction and incidence 38
3.6.1.1.2 Clinical and pathological features 39
3.6.1.1.3 Laboratory diagnosis 39
3.6.1.2 Graves' disease (thyrotoxicosis) 40
3.6.1.2.1 Introduction and incidence 40
3.6.1.2.2 Clinical and pathological features 40
3.6.1.2.3 Laboratory diagnosis 41
3.6.1.3 Primary myxoedema 41
3.6.2 Pernicious anaemia 42
3.6.2.1 Introduction and incidence 42
3.6.2.2 Clinical and pathological features 42
3.6.2.3 Laboratory diagnosis 43
3.6.3 Addison's disease (idiopathic
adrenal failure) 44
3.6.3.1 Introduction and incidence 44
3.6.3.2 Clinical and pathological features 44
3.6.3.3 Laboratory diagnosis 44
3.6.4 Primary ovarian failure 45
3.6.5 Male infertility 45
3.6.6 Insulin-dependent diabetes mellitus 45
3.6.6.1 Introduction and incidence 45
3.6.6.2 Clinical and pathological features 45
3.6.6.3 Laboratory diagnosis 47
3.6.7 Autoimmune insulin resistance 47
3.6.8 Autoimmune ophthalmopathies 48
3.6.9 Vitiligo 48
3.7 Intermediate group of autoimmune diseases 48
3.7.1 Myasthenia gravis 48
3.7.1.1 Introduction and incidence 48
3.7.1.2 Clinical and pathological features 49
3.7.1.3 Laboratory diagnosis 49
3.7.2 Goodpasture's syndrome 49
3.7.2.1 Introduction and incidence 49
3.7.2.2 Clinical and pathological features 50
3.7.2.3 Laboratory diagnosis 50
3.7.3 Autoimmune skin diseases:
pemphigus and pemphigoid 50
3.7.4 Multiple sclerosis 51
3.7.4.1 Introduction and incidence 51
3.7.4.2 Clinical and pathological features 51
3.7.4.3 Laboratory diagnosis 52
3.7.5 Autoimmune hemolytic anaemia 52
3.7.6 Idiopathic thrombocytopenic purpura 53
3.7.7 Primary biliary cirrhosis 53
3.7.7.1 Introduction and incidence 53
3.7.7.2 Clinical and pathological features 53
3.7.7.3 Laboratory diagnosis 54
3.7.8 Autoimmune hepatitis 54
3.7.8.1 Introduction and incidence 54
3.7.8.2 Clinical and pathological features 54
3.7.8.3 Laboratory diagnosis 55
3.7.9 Ulcerative colitis 55
3.7.10 Sj”gren's syndrome 55
3.7.10.1 Introduction and incidence 55
3.7.10.2 Clinical and pathological features 56
3.7.10.3 Laboratory diagnosis 56
3.8 Non organ-specific autoimmune diseases 56
3.8.1 Rheumatoid arthritis 57
3.8.1.1 Introduction and incidence 57
3.8.1.2 Clinical and pathological features 57
3.8.1.3 Laboratory diagnosis 59
3.8.2 Scleroderma (progressive systemic sclerosis) 59
3.8.2.1 Introduction and incidence 59
3.8.2.2 Clinical and pathological features 59
3.8.2.3 Laboratory diagnosis 60
3.8.3 Wegener's granulomatosis
and other vasculitides 60
3.8.4 Polymyositis-dermatomyositis 60
3.8.5 Systemic lupus erythematosus (SLE) 61
3.8.5.1 Introduction and incidence 61
3.8.5.2 Clinical and pathological features 61
3.8.5.3 Laboratory diagnosis 63
3.8.6 Discoid lupus erythematosus 64
3.8.7 Primary anti-phospholipid syndrome 65
3.8.8 Mixed connective tissue disease 65
3.9 Other diseases with a tentative autoimmune origin 65
3.9.1 Coeliac disease 65
3.9.1.1 Introduction and incidence 65
3.9.1.2 Clinical and pathological features 65
3.9.1.3 Laboratory diagnosis 66
3.9.2 Some cases of allergic rhinitis/asthma 66
3.9.3 Some infectious and parasitic disorders 67
3.10 Treatment of autoimmune diseases 67
CHAPTER 4 LABORATORY EVALUATION OF ALLERGY
4.1 Overview 69
4.2 Provocative tests 69
4.3 Skin testing 69
4.3.1 Introduction 69
4.3.2 Indications for skin testing 70
4.3.3 Skin testing procedures 70
4.3.3.1 Cutaneous skin tests 70
4.3.3.2 Intracutaneous skin tests 71
4.3.3.3 Reagents for skin testing 72
4.3.4 Interpretation of skin tests 72
4.3.5 Skin testing versus other methods 73
4.4 Total IgE and its measurement 74
4.4.1 Significance of total serum IgE values 74
4.4.2 Principles of immunoassays 75
4.4.2.1 General characteristics of immunoassays 75
4.4.2.2 Labelling 76
4.4.2.3 Bound-free separation 76
4.4.2.4 Competitive immunoassays 78
4.4.2.5 Immunometric immunoassays 78
4.4.2.6 Monoclonal Antibodies 79
4.4.2.7 Homogeneous immunoassays 81
4.4.2.8 Standardisation of immunoassays 81
4.4.2.9 Matrix effects 83
4.4.2.10 Sensitivities and detection limits 83
4.4.3 Commercial immunoassay formats 84
4.4.3.1 Kits and systems 84
4.4.3.2 Commercial radioimmunoassays 85
4.4.3.3 Commercial enzyme immunoassays 86
4.4.3.4 Commercial fluoroimmunoassays 86
4.4.3.5 Commercial luminescent immunoassays 87
4.4.3.6 Automation of commercial
immunoassay systems 87
4.4.4 Specific aspects of IgE assay 88
4.4.5 Survey of commercial kits for total IgE 90
4.5 Allergen-specific IgE and its measurement 91
4.5.1 Significance of allergen-specific IgE 91
4.5.2 Measurement of allergen-specific IgE 94
4.5.3 Survey of commercial methods for
specific IgE 99
4.5.3.1 Kabi Pharmacia Phadebas/Phadezym RAST 99
4.5.3.2 Kabi Pharmacia CAP system 99
4.5.3.3 Laboratorios Leti REINA 101
4.5.3.4 Diagnostic Products Corporation
AlaSTAT/AlaTOP 101
4.5.3.5 MAST Immunosystems CLA 103
4.5.3.6 Ventrex Turbo-RAST 103
4.5.3.7 Other specific IgE systems 103
4.6 Allergen-specific IgG and its measurement 104
4.6.1 Significance of allergen-specific IgG 104
4.6.2 Measurement of allergen-specific IgG 105
4.6.3 Survey of commercial methods for
specific IgG 105
4.7 Human anti-mouse antibodies (HAMA) 105
4.8 Assay of inflammatory markers 106
4.8.1 Histamine and histamine tryptase (HT) 106
4.8.2 Ascorbic acid 106
4.8.3 Myeloperoxidase (MPO) 107
4.8.4 Eosinophil cationic protein (ECP) 107
4.8.5 Platelet-activating factor (PAF) 108
4.8.6 Eicosanoids 108
4.8.7 CD23/soluble CD23 108
4.9 IgE and AIDS 109
CHAPTER 5 THE DETECTION OF AUTOANTIBODIES
5.1 Introduction 110
5.2 Traditional tests for autoantibody detection 110
5.2.1 Indirect immunofluorescence 110
5.2.1.1 The basic technique 110
5.2.1.2 Organ-specific and intermediate
autoantibodies 112
5.2.1.3 Non organ-specific autoantibodies 112
5.2.1.4 Commercial immunofluorescence kits 114
5.2.2 Functional autoantibody assays 115
5.2.3 Immunological autoantibody assays 115
5.2.3.1 Ouchterlony double diffusion 116
5.2.3.2 Countercurrent immunoelectrophoresis 116
5.2.3.3 Western blot assay (immunoblot) 117
5.2.3.4 Passive agglutination and
haemagglutination 117
5.2.4 Specialised assays 117
5.2.4.1 L.E. cell test 117
5.2.4.2 Coombs' antiglobulin test 118
5.2.4.3 Tests for rheumatoid factor 118
5.2.4.4 Tests for uveal and sperm antibodies 118
5.2.4.5 Detection of circulating
immune complexes 119
5.3 Immunoassays for autoantibodies 119
5.3.1 Advantages 119
5.3.2 Disadvantages 119
5.3.3 Recent developments 119
5.3.4 ANA/ENA autoantibody kits 120
5.3.5 Cardiolipin and pyruvate dehydrogenase
autoantibody kits 121
5.3.6 Organ-specific autoantibody kits 122
5.3.7 Rheumatoid factor (RF) kits 122
5.3.8 Circulating immune complexes (CIC) kits 122
5.3.9 Coeliac disease screening kits 123
5.3.10 Radioimmunoassays for autoantibodies 123
5.4 Products for HLA-DR typing 123
5.5 Cytokine and cytokine-receptor assays 124
CHAPTER 6 IMMUNE DEFICIENCY STATES
6.1 Introduction 126
6.2 Primary immunodeficiency 126
6.2.1 Global antibody deficiencies 126
6.2.2 Selective antibody deficiencies 129
6.2.3 Primary cellular immunodeficiencies 129
6.3 Secondary immunodeficiency 130
6.4 Immunodeficiency due to phagocyte defects 131
6.5 Immunodeficiency due to complement defects 132
6.6 Diagnosis of immunodeficiency 133
CHAPTER 7 COMPANIES AND MARKETS
7.1 Introduction 137
7.2 Market analysis 137
7.2.1 Demographic factors 137
7.2.2 Immune dysfunction in general practice 138
7.2.3 Sales analysis and forecasts to 1997 139
7.3 Abbott Laboratories 146
7.4 Ares-Serono SA 147
7.5 Becton Dickinson and Company 148
7.6 BioHyTech International Incorporated 149
7.7 Biomerica Incorporated 149
7.7.1 Parent company 149
7.7.2 Allergy Immuno Technologies Incorporated 150
7.8 bioMerieux 150
7.9 Boehringer Mannheim GmbH 151
7.10 Diagnostic Products Corporation 152
7.11 Diagnostics Pasteur SA 153
7.12 Immunotech SA 154
7.13 Hybritech Incorporated 154
7.14 Laboratorios LETI SA 156
7.15 MAST Immunosystems 157
7.16 Kabi-Pharmacia AB 158
7.17 Ventrex Laboratories Incorporated 159
APPENDIX 1 CORPORATE DIRECTORY A1
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