Peripheral‐blood cytopenia, an early indicator of inborn errors of immunity

Abstract

Summary Inborn errors of immunity (IEI) are inherited monogenic disorders resulting in defective immune response. Non‐infectious presentations are increasingly more apparent. Widely available, cost‐effective early indicators are needed. Peripheral‐blood cytopenia may be a presenting laboratory feature or an observed secondary phenomenon. This retrospective review of the South African Primary Immunodeficiency Registry (SAPIDR) aimed to assess the haematological indices at presentation and their association with the International Union of Immunological Societies (IUIS) 2019 IEI classification and mortality. Of 396 patients on the SAPIDR, 66% (n = 257) had available haematological results. Sixty percent were males and 85% under 18 years. A majority (53%) had predominantly antibody deficiency. At presentation, infection was prominent (86%) followed by cytopenia (62%). Neutropenia was associated with IUIS III [odds ratio (OR) 3.65, confidence interval (CI) 1.44–9.25], thrombocytopenia with IUIS II (OR 14.39, CI 2.89–71.57), lymphopenia with IUIS I (OR 12.16, CI 2.75–53.73) and pancytopenia with IUSI I (OR 12.24, CI 3.82–39.05) and IUIS II (OR 5.99, CI 2.80–12.76). Cytopenia showed shorter overall survival (OR 2.81, CI 1.288–4.16). Cytopenias that are severe, persistent, unusual and/or recurrent should prompt further investigation for IEI. The full blood count and leucocyte differential may facilitate earlier identification and serve as an adjunct to definitive molecular classification.

Infection and myelodysplasia: A case report of GATA2 deficiency in a South African patient

“…Identifying patients with germline variants that predispose them to MDS/AML requires recognition of out‐of‐the‐ordinary patterns of clinical features and organ dysfunction 1 . Severe, persistent, unusual and/or recurrent mycobacterial infections as well as peripheral blood cytopenia, in the absence of secondary immunodeficiency, should raise concern for a possible inborn error of immunity (IEI) 2 . In addition, severe and/or persistent cytopenias in the absence of an identifiable cause is an important indication for bone marrow examination (BME) 1,3 …”

“…cytopenia, in the absence of secondary immunodeficiency, should raise concern for a possible inborn error of immunity (IEI). 2 In addition, severe and/or persistent cytopenias in the absence of an identifiable cause is an important indication for bone marrow examination (BME). 1,3 In this case report we describe a patient with a history of disseminated non-tuberculous mycobacterial infection (NTM), lymphoedema, persistent cutaneous viral warts and pancytopenia, who was diagnosed with germline GATA2 deficiency.…”

Evans syndrome caused by a deleterious mutation affecting the adaptor protein SASH3

“…The view of the landscape of autoimmune cytopenias (AICs) is expanding rapidly with new insights into their pathogenic heterogeneity 1,2 and an increasing recognition of the role of genetically encoded immune defects (inborn errors of immunity [IEI]) in these. 3,4 Beyond their infectious manifestations, IEIs have the vastest overlap with AICs regarding autoimmune phenotypic appearances. 5 Especially the rare co-occurrence of autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia-defined as Evans syndrome (ES)-may represent the initial or predominant disease characteristic in paediatric patients with defined IEIs.…”

“…The view of the landscape of autoimmune cytopenias (AICs) is expanding rapidly with new insights into their pathogenic heterogeneity 1,2 and an increasing recognition of the role of genetically encoded immune defects (inborn errors of immunity [IEI]) in these 3,4 . Beyond their infectious manifestations, IEIs have the vastest overlap with AICs regarding autoimmune phenotypic appearances 5 .…”