History of primary immunodeficiency diseases.

PURPOSE OF REVIEW: This issue of Current Opinion in Allergy and Clinical Immunology is focused on primary immunodeficiency diseases (PIDs). Like every disorder, PID has its own specific history, starting with the discovery of agammaglobulinemia in 1952 and still expanding at a rapid pace, covering, at the time of this publication, more than 180 genetically determined disorders. However, as this report attempts to demonstrate, the history of PID is intertwined with the development of modern medicine and is the direct result of the innovative thinking of physician scientists who introduced new concepts in pathology, microbiology, biochemistry, and immunology, based on carefully designed experiments. As a consequence of the novel ideas put forth in the late 19th century, progress in public health, the discovery of antimicrobials, and the utilization of biologic products led to the recognition of genetically determined defects of Immunity and the design of effective treatment strategies. RECENT FINDINGS: The discovery of the structure of DNA, its replication, and the mapping of the human genome has transformed the field of PID into a predictable science of cutting edge therapies and diagnostic concepts. SUMMARY: This review illustrates the historic events that led to the discovery, classification, and molecular definition of PID.

The discovery of agammaglobulinaemia in 1952.

UNLABELLED: Fifty years ago a new disease, agammaglobulinaemia, was described. This was made possible by a great number of preceding technical innovations and theories on different fields of research, in particular haematology, microbiology/immunology and basic sciences. The widely used name "Bruton disease" credits one single man with a new observation which, however, was simultaneously made by several physicians. Agammaglobulinaemia was the first example of an immunodeficiency syndrome (IDS). Based on new facts, new ideas emerged which in turn gave rise to innovative research, concerning both clinical observations and basic problems. Many similar diseases, usually resulting from a genetic defect, were described. Since 1970, an International Committee appointed by the WHO, has, with periodic reassessments, been working on the classification of the syndromes. All participants of an efficient immune reaction can be deficient in individual patients, that is: antibodies, lymphocytes, phagocytes and complement. Basic scientists presented striking results concerning the structure and action of all elements mentioned above. CONCLUSION: mutual stimuli coming from observations in families and from gene technology have resulted in the elucidation of the genetic defects of most IDS. Recent results of genetic engineering seem to justify some hope for success in therapy.