DADA2 presenting as nonimmune hemolytic anemia with recurrent macrophage activation syndrome

Iyengar, Vaishnavi V.; Chougule, Akshaya; Gowri, Vijaya; Taur, Prasad; Prabhu, Sunil; Bodhanwala, Minnie; Desai, Mukesh

doi:10.1002/pbc.29461

Cited by 5 publications

(4 citation statements)

References 14 publications

(14 reference statements)

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“…Predisposition to viral infections may be justified by CD8+ alterations and Vgd2+T cells defect (12) together with the increased proportion of NK regulatory cells (12). These alterations could be also implicated in the reported HLH episodes (1,7,56,79).…”

Section: Discussionmentioning

confidence: 98%

“…These later cells are characterized by low cytotoxicity and high cytokine production, including TNF-α. It would be fascinating to investigate the functional role of this subset, particularly to understand the possible involvement in some peculiar clinical features described in DADA2, such as recurrent viral infections ( 12 , 27 , 54 , 55 ) and macrophage activation syndrome (MAS) ( 1 , 5 , 56 ) ( Figure 1 ).…”

Section: The Impact Of Ada2 Deficiency On the Cross Talk Between Inna...mentioning

confidence: 99%

“…These data, together with a remarkably lower proportion of Vγδ2+T cells ( 12 ), suggest that DADA2 CD8+ T cells may be involved in the development of refractory/recurrent viral infections observed in some patients ( 54 , 68 – 70 ). The defect in ADA2-deficient cytotoxic lymphocytes may be also linked to rare DADA2-associated manifestations, such as hemophagocytic lymphohistiocytosis (HLH) ( 1 , 5 , 56 ) or CD3+ CD8+ large granular lymphocytes ( 11 , 18 ).…”

Section: The Impact Of Ada2 Deficiency On the Cross Talk Between Inna...mentioning

confidence: 99%

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Adenosine Deaminase 2 Deficiency (DADA2): A Crosstalk Between Innate and Adaptive Immunity

et al. 2022

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Deficiency of Adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory disorder presenting with a broad spectrum of clinical manifestations, including immunodeficiency, vasculopathy and hematologic disease. Biallelic mutations in ADA2 gene have been associated with a decreased ADA2 activity, leading to reduction in deamination of adenosine and deoxyadenosine into inosine and deoxyinosine and subsequent accumulation of extracellular adenosine. In the early reports, the pivotal role of innate immunity in DADA2 pathogenic mechanism has been underlined, showing a skewed polarization from the M2 macrophage subtype to the proinflammatory M1 subtype, with an increased production of inflammatory cytokines such as TNF-α. Subsequently, a dysregulation of NETosis, triggered by the excess of extracellular Adenosine, has been implicated in the pathogenesis of DADA2. In the last few years, evidence is piling up that adaptive immunity is profoundly altered in DADA2 patients, encompassing both T and B branches, with a disrupted homeostasis in T-cell subsets and a B-cell skewing defect. Type I/type II IFN pathway upregulation has been proposed as a possible core signature in DADA2 T cells and monocytes but also an increased IFN-β secretion directly from endothelial cells has been described. So far, a unifying clear pathophysiological explanation for the coexistence of systemic inflammation, immunedysregulation and hematological defects is lacking. In this review, we will explore thoroughly the latest understanding regarding DADA2 pathophysiological process, with a particular focus on dysregulation of both innate and adaptive immunity and their interacting role in the development of the disease.

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Section: Discussionmentioning

confidence: 98%

Section: The Impact Of Ada2 Deficiency On the Cross Talk Between Inna...mentioning

confidence: 99%

Section: The Impact Of Ada2 Deficiency On the Cross Talk Between Inna...mentioning

confidence: 99%

See 1 more Smart Citation

Adenosine Deaminase 2 Deficiency (DADA2): A Crosstalk Between Innate and Adaptive Immunity

et al. 2022

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“…In a recent report, arthritic presentation mimicking systemic juvenile idiopathic arthritis has also been reported in DADA2 ( 53 ). Features of macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH), haemolytic anemia (non-immune), and persistent cytopenias (with a hypercellular bone marrow) were noted in this patient ( 53 ). MAS/HLH was also been reported in the first descriptions of this disease, besides many published and unpublished observations ( 1 , 26 , 38 ).…”

Section: Spectrum Of Clinical Manifestationsmentioning

confidence: 89%

Deficiency of Human Adenosine Deaminase Type 2 – A Diagnostic Conundrum for the Hematologist

et al. 2022

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Deficiency of adenosine deaminase type 2 (DADA2) was first described in 2014 as a monogenic cause of polyartertitis nodosa (PAN), early onset lacunar stroke and livedo reticularis. The clinical phenotype of DADA2 is, however, very broad and may involve several organ systems. Apart from vasculitis, children may present with i) Hematological manifestations (ii) Lymphoproliferation and iii) Immunodeficiencies. Patients with DADA2 can have variable patterns of cytopenias and bone marrow failure syndromes. Patients with DADA2 who have predominant haematological manifestations are associated with ADA2 gene variants that result in minimal or no residual ADA2 activity. Lymphoproliferation in patients with DADA2 may range from benign lymphoid hyperplasia to lymphoreticular malignancies. Patients may present with generalized lymphadenopathy, splenomegaly, autoimmune lymphoproliferative syndrome (ALPS) like phenotype, Hodgkin lymphoma, T-cell large granular lymphocytic infiltration of bone marrow and multicentric Castleman disease. Immunodeficiencies associated with DADA are usually mild. Affected patients have variable hypogammaglobulinemia, decrease in B cells, low natural killer cells, common variable immunodeficiency and rarely T cell immunodeficiency. To conclude, DADA2 has an extremely variable phenotype and needs to be considered as a differential diagnosis in diverse clinical conditions. In this review, we describe the evolving clinical phenotypes of DADA2 with a special focus on haematological and immunological manifestations.

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Macrophage Activation Syndrome in the Setting of Rheumatic Diseases

Chatham

2024

Advances in Experimental Medicine and Biology

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DADA2 presenting as nonimmune hemolytic anemia with recurrent macrophage activation syndrome

Cited by 5 publications

References 14 publications

Adenosine Deaminase 2 Deficiency (DADA2): A Crosstalk Between Innate and Adaptive Immunity

Adenosine Deaminase 2 Deficiency (DADA2): A Crosstalk Between Innate and Adaptive Immunity

Deficiency of Human Adenosine Deaminase Type 2 – A Diagnostic Conundrum for the Hematologist

Macrophage Activation Syndrome in the Setting of Rheumatic Diseases

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