Practical approach to diagnosis and management of primary immunodeficiency diseases

T M Rossouw,A J Theron,R Anderson

doi:10.4102/safp.v60i5.4914

Abstract

The occurrence of primary immunodeficiency diseases (PIDs) is low compared to that of immune-mediated disorders of autoimmune or atopic origin. However, progress in basic and clinical immunology over the past 3–4 decades has facilitated not only improved detection of PIDs, but has also created an awareness of an expanding spectrum of these conditions. Given that those who suffer from the most severe types of PID experience life-threatening microbial and viral infections usually from an early age, prompt recognition and definitive diagnosis enable implementation of appropriate prophylaxis and therapy, and, most importantly, corrective, immunorestoration using allogeneic haematopoietic stem cell transplantation. The purpose of the current review is therefore to alert family physicians to the presentation and types of PID that they may encounter in clinical practice, as well as to immunological screening procedures that can be undertaken to confirm or exclude the existence of the most common types of PID. This is followed by a consideration of prophylactic and therapeutic options and, finally, by a brief overview of gene therapy and gene-editing strategies that may offer alternatives to, or eventually replace, stem cell therapy.

Highlights

Primary immunodeficiency diseases (PIDs) are stable, heritable, disorders almost all of which affect a single gene critically involved in promoting optimal immune competence
PIDs are usually detected in early childhood, but, in some cases, diagnosis may only be made as late as the fifth decade, most notably in the case of common variable immunodeficiency (CVID)[3] and, albeit to a lesser extent, other PIDs such as chronic granulomatous disease (CGD).[4]
It has been estimated that around six million people worldwide are afflicted with a PID, even today in developed countries with the most advanced healthcare systems, the majority (70–90%) of those living with a PID remain undiagnosed, while somewhat surprisingly in the United States of America the estimated average time taken from onset of symptoms to diagnosis of a PID is 12.4 years.[4,5]

Summary

Introduction

Primary immunodeficiency diseases (PIDs) are stable, heritable, disorders almost all of which affect a single gene critically involved in promoting optimal immune competence. This involves administration of cytotoxic drugs, usually fludarabine, busulphan and/or cyclophosphamide, often in combination with anti-thymocyte globulin or with targeted radiation This strategy is used to eliminate host HSCs, thereby minimising rejection of donor HSCs, which occurs even in the setting of severe PIDs. a necessary prerequisite to successful HSCT, myeloablative conditioning does, pose the potential risk of severe infection, as does post-HSCT administration of immunosuppressive therapy, usually with www.tandfonline.com/oemd 47 The page number in the footer is not for bibliographic referencing cyclosporine, to prevent graft-versus-host disease mediated by donor-derived immunocompetent cells. The Standard Operating Procedure is available on Q-Pulse as IMM0394

Conclusion

Disclosure of interest