Inborn Errors of Immunity: A Practical Guide

By Asghar Aghamohammadi and Nima Rezaei

Awareness among clinicians about PIDs, which consist of more than 400 different entities, plays an important role in ensuring that patients receive a timely diagnosis. Furthermore, clinicians who are educated about PIDs can give their patients access to optimal management of their condition, thus helping the patient achieve a better quality-of-life and long-term prognosis.

Inborn Errors of Immunity: A Practical Guide provides the most up-to-date information for busy students, nurses, clinical residents, practicing physicians, and even basic researchers. Readers will benefit from a well-structured breakdown of complicated PID diseases, including approaches to their clinical signs/symptoms and immunologic/laboratory findings.

• Presents valuable contribution of more than 40 expert chapter authors, from top centers spanning five continents, each in a specific PID field
• Covers various aspects of PID using updated clinical guidelines and standard stepwise pipelines
• Focuses on the latest developments in the molecular diagnosis and pathogenesis of diseases, with easy explanation and schematic representation of defective signaling pathways
• Includes dedicated sections for clinical features and immunological tests with carefully-curated figures of PID manifestations, imaging, and histological/pathological illustrations to create the first PID medial-color atlas
• Summarizes the updated conventional and specific treatments and follow-up notes for different PID diseases

• Language: English
• Publisher: Academic Press
• Release date: Jan 22, 2021
• ISBN: 9780128231890

Book preview

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Chapter 1: Inborn errors of immunity

Asghar Aghamohammadia; Hassan Abolhassania,b    a Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran

b Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden

Abstract

Since the 1990s, the International Union of Immunological Societies (IUIS) expert committee, now called Inborn Errors of Immunity Committee, has published every other year classification of the primary immunodeficiency disorders (PIDs). This classification serves as a reference for clinical immunologists and researchers worldwide. There are now more than 450 single-gene PIDs underlying phenotypes as diverse as infection, autoimmunity, allergy, lymphoproliferation, and malignancy. We, herein, provide comprehensive diagnostic and therapeutic algorithms to approach these patients based on the revised 2020 IUIS classification.

Keywords

IUIS; PIDs; Clinical approach; Immunodeficiency; Recurrent infections; Differential diagnosis; Noninfectious complications

1.1: Introduction on inborn errors of immunity

Asghar Aghamohammadi and Hassan Abolhassani

Since the 1990s, the International Union of Immunological Societies (IUIS) expert committee,¹ now called Inborn Errors of Immunity Committee, has published every other year classification of the primary immunodeficiency disorders (PIDs). This classification serves as a reference for clinical immunologists and researchers worldwide. There are now more than 450 single-gene PIDs underlying phenotypes as diverse as infection, autoimmunity, allergy, lymphoproliferation, and malignancy. We, herein, provide comprehensive diagnostic and therapeutic algorithms to approach these patients based on the revised 2020 IUIS classification.² Moreover, educative illustrations and comprehensive atlas of patients’ complications are provided. PIDs were long considered as rare diseases; however, recent studies tend to show that they are more common than generally thought. As the number of PIDs are quickly increasing, and at an even faster pace since the advent of next-generation sequencing, this phenotypic classification requires revision at the same pace as the classical immunologic classification. An updated algorithm was assigned to each of the nine main groups of the classification in each chapter of this book including:

•Combined immunodeficiencies (see Chapter 2).

•Combined immunodeficiencies with syndromic features (see Chapter 3).

•Predominantly antibody deficiencies (see Chapter 4).

•Diseases of immune dysregulation (see Chapter 5).

•Congenital defects of phagocytes (see Chapter 6).

•Defects in intrinsic and innate immunity (see Chapter 7).

•Autoinflammatory diseases (see Chapter 8).

•Complement deficiencies (see Chapter 9).

•Phenocopies of inborn errors of immunity (see Chapter 10).

The algorithms presented in each chapters are, at the very least, a list of the most common disorders that may cause a given PID symptom or sign. As such, however, they are not all-inclusive. Rare or unusual conditions are included based on expert’s opinions in each field; however, the reader is referred to other review articles of the differential diagnosis for specific PIDs for a more complete list of diagnostic possibilities. The list of differential diagnoses and possibilities is broken down by the presence or absence of additional clinical or immunologic properties. The reader should be aware that any specific patient may not present with an additional symptom necessary for this analysis, and, therefore, the entire list of possibilities must still be considered preferably with an unbiased genetic analysis using next-generation sequencing. Alternatively, the PID patient may present with the additional symptom but still have one of the other disorders on the diagnostic tree; therefore, at all times, the clinician should maintain an index of suspicion that the patient could have any one of the disorders listed on the page and not exclude any of the possibilities completely until a correct genetic diagnosis has been made.

We have provided also in a separate chapter, a guideline toward general treatment and management of PID patients (see Chapter 11).

In this chapter, we started this book with a summary of recommendations and guidelines for suspicion to PID diagnosis in the neonate, children, and adults. Because the infections are the main hallmark of PIDs, the following topics are first summarized in these clinical guidelines: Approach to recurrent infectious (see Fig. 1.1) approach to warning infectious complications (see Fig. 1.2) and approach to opportunistic infections (see Fig. 1.3). Because in all PID patients, other acquired causes of immunodeficiency should be excluded, we have provided an approach to exclude secondary immunodeficiencies (see Fig. 1.4). Of note, clinical immunologists and researchers should be aware of other main noninfectious features of PIDs and their common underlying pathogenic mechanisms; therefore, we have also depicted an approach to noninfectious complications of PIDs (see Fig. 1.5). Using these clinical guidelines, a treating physician will be able to identify the most susceptible patient with PID and then navigate correctly to the appropriate above-mentioned chapters for further clinical, immunologic, and genetic evaluations.

Fig. 1.1 Abstracted guideline for the approach of recurrent infections to exclude nonPID disorders. ³ – ⁶

Fig. 1.2 Abstracted guideline for the approach of warning infectious complications associated with PID. ⁶ – ⁸

Fig. 1.3 Abstracted guideline for the approach of opportunistic infections suggestive of PID. ³ , ⁸ , ⁹

Fig. 1.4 Conditions associated with recurrent infections due to secondary immunodeficiency that should be excluded in PID patients. ¹⁰ – ¹²

Fig. 1.5 Approach to noninfectious complications of PIDs and their probable molecular defects. ⁸ , ¹³

References

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