IMMUNOGLOBULINS IN HEALTH AND DISEASE

Chairman' Dr. B. G. Alton (Dublin).

Recent Advances in Diagnostic Immunology: R. Wright (Southampton).

An Immunological Approach to the Treatment of Malignant Disease : Morag

Chisholm (Oxford).

Panel Discussion �9 Chairman, Speakers and Dr. J. Greally (Dublin).

We now come to the last session of this Symposium and by the look of the captive talent I have on the platform here this may well be a very exciting session. This is the one to do with immunology and cer[ainly this is a branch of medicine which is expanding very rapidly in the fast few years. I would now like to introduce Dr. Ralph Wright, Professor of Medi- cine, Southampton, who will talk to us on recent development in diagnostic immunology.

RECENT ADVANCES IN DIAGNOSTIC IMMUNOLOGY

Ralph Wright

Professorial Medical Unit, Royal South Hants Hospital, Southampton.

T ESTS used in the diagnosis of immunological disorders can be classified under three headings :

a) Those used in the assessment of the immune deficiency disorders, either associated with immunoglobulin disturbances or distur- bances of cell-mediated immunity;

b) Those due to hypersensitivity reactions, either to exogenous anti- gens or autoantigens; and

c) Those used to detect turnout or viral antigens.

In the present report the current status of immunological techniques in the diagnosis of hypersensitivy reactions will be reviewed with certain specific examples and the potential of immunological techniques in the detection of turnout and viral antigens will be briefly discussed. Hypersen- sitivity reactions may be broadly classified into four types (Table I). In vitro tests for specific circulating antibodies mediating these reactions are limited. Circulating IgE levels and complement levels may provide indirect evidence in Type 1 and Type 3 reactions, and specific precipitins have proved of value in diagnosis in Type 3 reactions associated with extrinsic

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98 IRISH JOURNAL OF MEDICAL SCIENCE--SUPPLEMENT, MAY 1973

alveolitis, such as farmer's lung and bird fanciers' disease. In some in- stances, for example Goodpasture's syndrome and Systemic Lupus Ery- thematosus, the deposition of antigen or antibody in the glomeruli can be demonstrated by immunofluorescence of renal biopsy tissue, and the same applies to certain skin lesions, such as arteritis and erythema nodosum.

TABLE I

Hypersensitivity Reactions

Disease Diagnostic Tests Used

TYPE I ANAPHYLACTIC Atopic disorders

TYPE II CYTOTOXIC

TYPE III IMMUNE COMPLEX

TYPE IV CELL-MEDIATED

Sedormid purpura Haemolytic anaemia Goodpasture's syndrome

Extrinsic alveolitis Glomerular lesions Arteritis Erythema nodosum

Skin tests Basophil degranulation tests IgE bevels

Specific cytotoxic anti- bodies

Specific precipitins Immune complex deposits Complement

Bacterial Specific lymphocyte trans- Autoimmune disease formation Contact dermatitis Specific leucocyte migra-

tion

Circulating autoantibodies, although not themselves necessarily con- cerned with pathogenesis and often reacting with intracellular constituents, may nevertheless be of value in diagnosis. Some, such as antinuclear factor and smooth muscle antibody, merely give a general indication of a sensitivity reaction of a particular type associated with collagen or liver disease. Other autoimmune reactions show a high degree of specificity for a particu'.ar disease (Table II).

The presence of thyroid antibodies at high titre invariably indicate histo- logical evidence of thyroiditis, even though clinically apparent thyroid disease may not be present. Similarly, the presence of gastric parietal cell antibodies indicates gastric mucosal damage. Intrinsic factor antibodies may be present in serum or in gastric juice and are highly specific for pernicious anaemia or latent pernicious anaemia. Indeed, the intrinsic factor antibody may be present in gastric juice when it is absent from the serum and may play an active role in pathogene~sis of pernicious anameia by blocking the absorption of serum vitamin B,._,, even if it does not directly produce the histological damage in the stomach. Antibodies reacting with thymic epithelial cells and muscle when present at high titre are of consi- derable value in the diagnosis of myasthenia gravis and are related to the severity of the disease, being of highest titre in patients with a thymoma or with carcinoma of the thymus.

IMMUNOGLOBULINS IN HEALTH AND DISEASE

TABLE II

Autoimmune Reactions with High Specificity

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Disease Autoantibodies

Thyroid Disease

Pernicious Anaemia and Gastritis

Addison's Disease

Myasthenia G ravis

Primary Biliary Cirrhosis

Pemphigus Vulgaris

Pemphigoid

Systemic Lupus Erythematosus

Thyroglobulin Thyroid Cytoplasmic LATS

Intrinsic Factor Gastric Parietal Cell

Adrenal Cortex

Skeletal Muscle Thymic Myoid Cells

Mitochondria

Skin Intercellular Substance

Skin Basement Membrane

Na.tive DNA

Technical difficulties still l imit our ability to detect cell-mediated hyper- sensitivity reactions, whether to exogenous or autoantigens. The situation may be complex involving circu!ating cytotoxic antibody, macrophages and lymphocytes. Specific lymphocyte transformation in response to the antigen or impairment of leucocyte migration may be used but have practi- cal limitations.

Currently there is considerable interest in the role of immunological msthods in the diagnosis of cancer and of antigens of viruses which have not been isolated in culture. The Australia antigen provides the best recent example of the latter group. It was discovered by a geneticist working in a cancer research institute and was init ially thought to be a new s~rum protein allotype but was subsequently shown to be specif icial ly associated with the serum hepatitis virus (virus B).

Much research is currently being directed towards attempts to detect turnout specific antigens by immunological means, but few examples have besn clearly identified. Foetal antigens such as the carcino-embryonic antigen (CEA) and alpha-feto-protein may prove to be of value in diagnosis but are not specific for a particular tumour. Another promising approach has been the use of immunological metho~ls to detect antigens associated with oncogenic viruses. Considerab!e advances are likely in this field within the next decade.