Abstract
There are now nearly 300 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. For each of these five categories, a growing variety of phenotypes are ascribed to Primary Immunodeficiency Diseases (PID), making PIDs a rapidly expanding field of medicine. The International Union of Immunological Societies (IUIS) PID expert committee (EC) has published every other year a classification of these disorders into tables, defined by shared pathogenesis and/or clinical consequences. In 2013, the IUIS committee also proposed a more user-friendly, phenotypic classification, based on the selection of key phenotypes at the bedside. We herein propose the revised figures, based on the accompanying 2015 IUIS PID EC classification.
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Introduction
Human Primary Immunodeficiency Diseases (PID) comprise at least 300 genetically-defined single-gene inborn errors of immunity [1]. Long considered as rare diseases, recent studies tend to show that they are more common than generally thought, if only by their rapidly increasing number [2]. They may be even more common, if we consider the emerging monogenic determinants leading to common infectious diseases, such as severe influenza [3]; autoimmune diseases, such as systemic lupus erythematosus [4], and auto-inflammatory diseases, such as Crohn’s disease [5]. The International Union of Immunological Societies (IUIS) PID expert committee has proposed a PID classification [1], which facilitates clinical research and comparative studies world-wide; it is updated every other year to include new disorders or disease-causing genes. This classification is organized in tables, each of which groups PIDs that share a given pathogenesis. As this classification may be cumbersome for use by the clinician at the bedside, the IUIS PID expert committee recently proposed a phenotypic complement to its classification [6]. As the number of PIDs is quickly increasing, and at an even faster pace since the advent of next-generation sequencing, the phenotypic classification from 2013 became outdated and requires revision at the same pace as the classical IUIS classification. Our original phenotypic classification proved successful, which placed it in the 96th percentile for citation rank in Springer journals [7]. Given the success of our user-friendly classification of PIDs, providing a tree-based decision-making process based on the observation of clinical and biological phenotypes, we present here an update of these figures, based on the accompanying 2015 PID classification.
Methodology
We included all diseases included in the 2015 update of the IUIS PID classification [1], keeping the nine major categories unchanged. In addition, we considered other articles proposing a PID classification published recently [8, 9]. An algorithm was assigned to each of the nine main groups of the classification and the same color was used for each group of similar conditions. Disease names are presented in red and genes in bold. In addition, we classed diseases or genes from most common to less common, at the best of our knowledge [10, 11]. These algorithms were first established by a small committee; then validated by one or two experts for each figure.
Discussion
Since our 2013 study, 70 new diseases have been included in the 2015 classification. Four disorders have been removed, as the reports concerning associated immunodeficiency or genetic base were not confirmed. We also eliminated duplication of a disease in more than one figure and profoundly revised some figures, following the 2015 IUIS classification.
Conclusion
The IUIS PID expert committee developed this phenotypic classification in order to help clinicians at the bedside to diagnose PIDs but also to promote collaboration with national and international research centers. Needless to say, the expert committee encourages the development of other types of PID classification. Indeed, given the success encountered by the two current IUIS classifications, others classifications are likely to be useful and complementary.
Abbreviations
- αFP:
-
Alpha- fetoprotein
- Ab:
-
Antibody
- AD:
-
Autosomal dominant inheritance
- ADA:
-
Adenosine deaminase
- Adp:
-
Adenopathy
- ALPS:
-
Autoimmune lymphoproliferative syndrome
- AML:
-
Acute myeloid leukemia
- Anti PPS:
-
Anti- pneumococcus antibody
- AR:
-
Autosomal recessive inheritance
- BCG:
-
Bacilli Calmette-Guerin
- BL:
-
B lymphocyte
- CAMPS:
-
CARD14 mediated psoriasis
- CANDLE:
-
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome
- CAPS:
-
Cryopyrin-associated periodic syndromes
- CBC:
-
Complete blood count
- CD:
-
Cluster of differentiation
- CDG-IIb:
-
Congenital disorder of glycosylation, type IIb
- CGD:
-
Chronic granulomatous disease
- CID:
-
Combined immunodeficiency
- CINCA:
-
Chronic infantile neurologic cutaneous and articular syndrome
- CMC:
-
Chronic mucocutaneous candidiasis
- CMF:
-
Flow cytometry available
- CMV:
-
Cytomegalovirus
- CMML:
-
Chronic myelomonocytic leukemia
- CNS:
-
Central nervous system
- CSF:
-
Cerebrospinal fluid
- CT:
-
Computed tomography
- CTL:
-
Cytotoxic T-lymphocyte
- DA:
-
Duration of attacks
- Def:
-
Deficiency
- DHR:
-
DiHydroRhodamine
- Dip:
-
Diphtheria
- DITRA:
-
Deficiency of interleukin 36 receptor antagonist
- 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
- FILS:
-
Facial dysmorphism, immunodeficiency, livedo, and short stature
- FISH:
-
Fluorescence in situ hybridization
- GI:
-
Gastrointestinal
- GOF:
-
Gain-of-function
- HHV8:
-
Human herpes virus type 8
- Hib:
-
Haemophilus influenzae serotype b
- HIDS:
-
Hyper IgD syndrome
- HIES:
-
Hyper IgE syndrome
- HIGM:
-
Hyper Ig M syndrome
- HLA:
-
Human leukocyte antigen
- HLH:
-
Hemophagocytic lymphohistiocytosis
- HPV:
-
Human papilloma virus
- HSM:
-
Hepatosplenomegaly
- HSV:
-
Herpes simplex virus
- HUS:
-
Hemolytic uremic syndrome
- Hx:
-
Medical history
- IBD:
-
Inflammatory bowel disease
- IFNγ:
-
Interferon gamma
- Ig:
-
Immunoglobulin
- IL:
-
Interleukin
- IUGR:
-
Intrauterine growth retard
- LAD:
-
Leukocyte adhesion deficiency
- LOF:
-
Loss-of-function
- MC:
-
Molluscum contagiosum
- MKD:
-
Mevalonate kinase deficiency
- MSMD:
-
Mendelian susceptibility to mycobacterial disease
- MWS:
-
Muckle-wells syndrome
- N:
-
Normal, not low
- NK:
-
Natural killer
- NKT:
-
Natural killer T cell
- NN:
-
Neonatal
- NOMID:
-
Neonatal onset multisystem inflammatory disease
- NP:
-
Neutropenia
- PAPA:
-
Pyogenic sterile arthritis, pyoderma gangrenosum, acne syndrome
- PMN:
-
Neutrophils
- SCID:
-
Severe combined immuno deficiency
- Sd:
-
Syndrome
- SLE:
-
Systemic lupus erythematosus
- SPM:
-
Splenomegaly
- Staph:
-
Staphylococcus sp.
- subcl:
-
Subclass
- TCR:
-
T-cell receptor
- Tet:
-
Tetanus
- T:
-
T lymphocyte
- TNF:
-
Tumor necrosis factor
- TRAPS:
-
TNF receptor-associated periodic syndrome
- VZV:
-
Varicella zoster virus
- WBC:
-
White blood cells
- XL:
-
X-linked
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Bousfiha, A., Jeddane, L., Al-Herz, W. et al. The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies. J Clin Immunol 35, 727–738 (2015). https://doi.org/10.1007/s10875-015-0198-5
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DOI: https://doi.org/10.1007/s10875-015-0198-5