Patient-centred screening for primary immunodeficiency: a multi-stage diagnostic protocol designed for non-immunologists

Abstract

Efficient early identification of primary immunodeficiency disease (PID) is important for prognosis, but is not an easy task for non-immunologists. The Clinical Working Party of the European Society for Immunodeficiencies (ESID) has composed a multi-stage diagnostic protocol that is based on expert opinion, in order to increase the awareness of PID among doctors working in different fields. The protocol starts from the clinical presentation of the patient; immunological skills are not needed for its use. The multi-stage design allows cost-effective screening for PID within the large pool of potential cases in all hospitals in the early phases, while more expensive tests are reserved for definitive classification in collaboration with an immunologist at a later stage. Although many PIDs present in childhood, others may present at any age. The protocols presented here are therefore aimed at both adult physicians and paediatricians. While designed for use throughout Europe, there will be national differences which may make modification of this generic algorithm necessary.

Fig. 1

Grey shading: collaboration with an immunologist is highly recommended for this step. ANA, anti-nuclear antibodies; AP₅₀, haemolytic assay of alternative pathway of complement; AT, ataxia telangiectasia; CD, cluster of differentiation; CH₅₀, haemolytic assay of classical pathway of complement; CVID, common variable immunodeficiency; ENT, ear, nose and throat; HIGM, hyper-IgM syndrome; ICF, syndrome of immunodeficiency, centromeric instability and facial dysmorphism; Ig, immunoglobulin; IRAK4, interleukin-1 receptor-associated kinase 4; L, ligand; MBL, mannan binding lectin; SLE, systemic lupus erythematosus; THI, transient hypogammaglobulinaemia of infancy; TLR, Toll-like receptor; XLP, X-linked lymphoproliferative syndrome.

Fig. 2

Grey shading: collaboration with an immunologist is highly recommended for this step. ADA, adenosine deaminase; AIDS, acquired immunodeficiency syndrome; BAL, bronchoalveolar lavage; CD, cluster of differentiation; CMC, chronic mucocutaneous candidiasis; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; Ig, immunoglobulin; IFN, interferon; IL, interleukin; JAK, janus kinase; L, ligand; PCR, polymerase chain reaction; PNP, purine nucleoside phosphorylase; RAG, recombination activating gene; SCID, severe combined immunodeficiency; SCT, stem cell transplantation; STAT, signal transducer and activator of transcription; WAS, Wiskott–Aldrich syndrome; Zap, zeta-associated protein.

Fig. 3

Grey shading: collaboration with an immunologist or hematologist is highly recommended for this step. ANA, anti-nuclear antibody; ANCA, anti-neutrophil cytoplasmic autoantibodies; C, complement component; CD, cluster of differentiation; CGD, chronic granulomatous disease; CVID, common variable immunodeficiency; FMF, familial Mediterranean fever; G–CSF, granulocyte–colony-stimulating factor; G6PD, glucose-6-phosphate dehydrogenase; MPO, myeloperoxidase; NADPH, nicotinamide adenine dinucleotide phosphate; PFAPA, periodic fever–aphthous stomatitis–pharyngitis–cervical adenopathy; RF, rheumatoid factor; SBDS, Schwachman–Bodian–Diamond syndrome; SGD, neutrophil-specific granule deficiency; sLeX, sialyl Lewis X; TLR, Toll-like receptor.