A Phenotypic Approach for IUIS PID Classification and Diagnosis: Guidelines for Clinicians at the Bedside (original) (raw)

Abstract

The number of genetically defined Primary Immunodeficiency Diseases (PID) has increased exponentially, especially in the past decade. The biennial classification published by the IUIS PID expert committee is therefore quickly expanding, providing valuable information regarding the disease-causing genotypes, the immunological anomalies, and the associated clinical features of PIDs. These are grouped in eight, somewhat overlapping, categories of immune dysfunction. However, based on this immunological classification, the diagnosis of a specific PID from the clinician’s observation of an individual clinical and/or immunological phenotype remains difficult, especially for non-PID specialists. The purpose of this work is to suggest a phenotypic classification that forms the basis for diagnostic trees, leading the physician to particular groups of PIDs, starting from clinical features and combining routine immunological investigations along the way. We present 8 colored diagnostic figures that correspond to the 8 PID groups in the IUIS Classification, including all the PIDs cited in the 2011 update of the IUIS classification and most of those reported since.

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Abbreviations

αFP:

Alpha- fetoprotein

Ab:

Antibody

AD:

Autosomal dominant inheritance

ADA:

Adenosine deaminase

Adp:

Adenopathy

AIHA:

Auto-immune hemolytic anemia

AML:

Acute myeloid leukemia

Anti PSS:

Anti- pneumococcus polysaccharide antibodies

AR:

Autosomal recessive inheritance

BL:

B lymphocyte

CAPS:

Cryopyrin-associated periodic syndromes

CBC:

Complete blood count

CD:

Cluster of differentiation

CGD:

Chronic granulomatous disease

CID:

Combined immunodeficiency

CINCA:

Chronic infantile neurologic cutaneous and articular syndrome

FCM*:

Flow cytometry available

CMML:

Chronic myelo-monocytic leukemia

CNS:

Central nervous system

CVID:

Common variable immunodeficiency disorders

CT:

Computed tomography

CTL:

Cytotoxic T-lymphocyte

DA:

Duration of attacks

Def:

Deficiency

DHR:

DiHydroRhodamine

Dip:

Diphtheria

EBV:

Epstein-barr virus

EDA:

Anhidrotic ectodermal dysplasia

EDA-ID:

Anhidrotic ectodermal dysplasia with immunodeficiency

EO:

Eosinophils

FA:

Frequency of attacks

FCAS:

Familial cold autoinflammatory syndrome

FISH:

Fluorescence in situ hybridization

GI:

Gastrointestinal

Hib:

Haemophilus influenzae serotype b

HIDS:

Hyper IgD syndrome

HIES:

Hyper IgE syndrome

HIGM:

Hyper Ig M syndrome

HLA:

Human leukocyte antigen

HSM:

Hepatosplenomegaly

Hx:

Medical history

Ig:

Immunoglobulin

IL:

Interleukin

LAD:

Leukocyte adhesion deficiency

MKD:

Mevalonate kinase deficiency

MSMD:

Mendelian susceptibility to mycobacteria disease

MWS:

Muckle-Wells syndrome

N:

Normal, not low

NK:

Natural killer

NKT:

Natural killer T cell

NN:

Neonate

NOMID:

Neonatal onset multisystem inflammatory disease

NP:

Neutropenia

PAPA:

Pyogenic sterile arthritis pyoderma gangrenosum, Acne syndrome

PMN:

Neutrophils

PT:

Platelet

SCID:

Severe combined immune deficiencies

Sd:

Syndrome

SLE:

Systemic lupus erythematosus

SPM:

Splenomegaly

Subcl:

IgG subclass

TCR:

T-cell receptor

Tet:

Tetanus

TL:

T lymphocyte

TNF:

Tumor necrosis factor

TRAPS:

TNF receptor-associated periodic syndrome

WBC:

White blood cells

XL:

X-linked

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Acknowledgments

We thank Dr Capucine Picard and Dr Claire Fieschi for their contribution to this work.

Author information

Authors and Affiliations

  1. Clinical Immunology Unit, A. Harouchi Children Hospital, Ibn Rochd Medical School, King Hassan II University, 60, rue 2, Quartier Miamar, Californie, Casablanca, Morocco
    Ahmed Aziz Bousfiha
  2. Clinical Immunology Unit, A. Harouchi Children Hospital, Ibn Rochd Medical School, King Hassan II University, Casablanca, Morocco
    Leïla Jeddane & Fatima Ailal
  3. Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
    Waleed Al Herz
  4. Allergy and Clinical Immunology Unit, Department of Pediatrics, Al-Sabah Hospital, Kuwait City, Kuwait
    Waleed Al Herz
  5. Department of Pediatrics, University of Tennessee College of Medicine, Memphis, TN, USA
    Mary Ellen Conley
  6. Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA
    Mary Ellen Conley
  7. Department of Medicine and Pediatrics, Mount Sinai School of Medicine, New York, NY, USA
    Charlotte Cunningham-Rundles
  8. Meyer’s Children Hospital– Technion, Haifa, Israel
    Amos Etzioni
  9. Pediatric Hematology- Immunology Unit, Hôpital Necker Enfants-Malades, Assistance Publique–Hôpital de Paris, Necker Medical School, Paris Descartes University, Paris, France
    Alain Fischer
  10. Group of Primary Immunodeficiencies, University of Antioquia, Medellín, Colombia
    Jose Luis Franco
  11. Division of Immunology, Children’s Hospital Boston, Boston, MA, USA
    Raif S. Geha & Luigi D. Notarangelo
  12. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
    Lennart Hammarström
  13. Department of Pediatrics, National Defense Medical College, Saitama, Japan
    Shigeaki Nonoyama
  14. Department of Pediatrics, University of Washington and Seattle Children’s Research Institute, Seattle, WA, USA
    Hans D. Ochs
  15. Division of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada
    Chaim M. Roifman
  16. Division of Immunology, University Children’s Hospital, Zürich, Switzerland
    Reinhard Seger
  17. Department of Allergy and Immunology, Royal Children’s Hospital Melbourne, Melbourne, VIC, Australia
    Mimi L. K. Tang
  18. Murdoch Children’s Research Institute, Melbourne, VIC, Australia
    Mimi L. K. Tang
  19. Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
    Mimi L. K. Tang
  20. Department of Pediatrics, University of California San Francisco and UCSF Benioff Children’s Hospital, San Francisco, CA, USA
    Jennifer M. Puck
  21. Clinical Immunology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK
    Helen Chapel
  22. The Manton Center for Orphan Disease Research, Children’s Hospital Boston, Boston, MA, USA
    Luigi D. Notarangelo
  23. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
    Jean-Laurent Casanova
  24. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Medical School, University Paris Descartes and INSERM U980, Paris, France
    Jean-Laurent Casanova

Authors

  1. Ahmed Aziz Bousfiha
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  2. Leïla Jeddane
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  3. Fatima Ailal
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  4. Waleed Al Herz
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  5. Mary Ellen Conley
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  6. Charlotte Cunningham-Rundles
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  7. Amos Etzioni
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  8. Alain Fischer
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  9. Jose Luis Franco
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  10. Raif S. Geha
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  11. Lennart Hammarström
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  12. Shigeaki Nonoyama
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  13. Hans D. Ochs
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  14. Chaim M. Roifman
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  15. Reinhard Seger
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  16. Mimi L. K. Tang
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  17. Jennifer M. Puck
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  18. Helen Chapel
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  19. Luigi D. Notarangelo
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  20. Jean-Laurent Casanova
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Corresponding author

Correspondence toAhmed Aziz Bousfiha.

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Bousfiha, A.A., Jeddane, L., Ailal, F. et al. A Phenotypic Approach for IUIS PID Classification and Diagnosis: Guidelines for Clinicians at the Bedside.J Clin Immunol 33, 1078–1087 (2013). https://doi.org/10.1007/s10875-013-9901-6

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