Table 2.

Causes of secondary antibody deficiency

B cell lymphoproliferative disease	Protein loss	Lymphatic circulation	Increased catabolism	Drug‐related
Chronic lymphocytic leukaemia (CLL) 20	Renal loss Nephrotic syndrome	Intestinal lymphangiectasia	Myotonic dystrophy 21, 22	Therapies targeting B cells Rituximab 23, 24, 25 CD19‐targeted chimeric antigen receptor T cells (CART) 26, 27
Non‐Hodgkins lymphoma, Hodgkins lymphoma, Diffuse large B cell lymphoma Follicular lymphoma Mantle cell lymphoma Marginal zone lymphoma Burkitt's lymphoma 28	Gastrointestinal loss Crohn's disease Ulcerative colitis Intestinal lymphangectasia Turner's syndrome Noonan's syndrome Klippel–Trenauny syndrome Hennekam syndrome Coeliac disease Enteric infection Menetrier's disease 29, 30, 31	Proteus syndrome 32 Yellow nail syndrome Noonan's syndrome		Mycophenolate 33 Cyclophosphamide 25 Corticosteroids 34 Sulphasalazine Gold D‐penicillamine Chlorpromazine Methotrexate Clozapine 28, 35, 36, 37, 38 Imatinib 39 Atacicept 40, 41 Fludarabine and other chemotherapy
Multiple myeloma Smouldering myeloma Monoclonal gammopathy of undetermined significance (MGUS) 42, 43, 44, 45		Chylothorax 46, 47		Anti‐epileptic medication Phenytoin Carbamazepine Sodium valproate Lamotrigine 48, 49

The main categories underlying secondary antibody deficiency (SAD) are shown, which include causes related to decreased production as well as increased loss or catabolism. The individual causes are very numerous and patients may therefore present with SAD from a broad range of clinical specialities, which would include Haematology, Oncology, Medicine, Rheumatology, Nephrology, primary care and others. The specialities with the highest levels of SAD are those where the disease itself (e.g. CLL, myeloma) and/or its treatment are associated with antibody deficiency. Similarly, combination and/or prolonged immunosuppressive therapy as required, for example, in transplantation, granulomatosis with polyangiitis (GPA) or neuromyelitis optica (NMO) will have a higher rate of SAD. Not shown in the Table are the transient causes of SAD, which occur in relation to interventions where intravenous fluid or blood may be needed in relation to surgery or intensive‐care settings 28.