Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
Humans ; Adenosine Deaminase/deficiency* ; Monocytes/cytology* ; Cell Differentiation ; Intercellular Signaling Peptides and Proteins/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Biomarkers/metabolism* ; Macrophages/metabolism* ; Pneumonia/metabolism*

OBJECTIVETo enhance the knowledge of adenosine deaminase (ADA) deficiency associated severe combined immunodeficiency (SCID) with disseminated varicella infection after vaccination.

METHODSWith case report and review of literature, the background knowledge, clinical and laboratory findings, diagnosis and treatment of ADA-deficient SCID were discussed.

RESULTSThe patient had the condition with failure to thrive. The main complaint was more than three weeks of fever and rash. He had received the live attenuated Oka strain varicella vaccination approximately two weeks before the onset of rash. Varicella infection was confirmed with direct immunofluorescence assay. The patient had mild leukopenia, with 3% lymphocytes. The initial immunologic workup included decreased IgG, IgM and IgA, abnormal expanded lymphocyte enumeration which confirmed the reduction of CD3, CD4, CD8, CD19 and CD56. Enzyme testing for ADA activity showed remarkably low level in the hemolysate, as well as increased levels of deoxyadenosine nucleotides.

CONCLUSIONADA-deficient SCID has some characteristic clinical and laboratory findings. Management options for ADA-deficient SCID include hematopoietic stem cell transplantation, enzyme replacement therapy and gene therapy. Immunodeficiency should be considered in children with severe failure-to-thrive. Live vaccine administration should be avoided in patients with immunodeficiency.

Adenosine Deaminase ; deficiency ; African Americans ; Chickenpox ; complications ; etiology ; Humans ; Infant ; Male ; Severe Combined Immunodeficiency ; complications ; Vaccination ; adverse effects

Psoriasis has been known to have various humoral and cellular immune abnormalities. And adenosine deaminase (ADA) activities are known to be decreased in immune deficiency diseases. The present study was designed to measure the activities of ADA in sera and erythrocytes of psoriasis patients by Giustiss method. There were no significant differences in the erythrocytes ADA activities between normal subjects (9, Gp+4 43 units/10 cells) and psoriasis patients (7, 29+3. 64 units /10 cells). The ADA activities in sera of the psoriasis patients (13. 15+3. 43 units/ L) showed lowered activities than those of normal subjects (20. 44-2, 07 units/L).
Adenosine Deaminase* ; Adenosine* ; Deficiency Diseases ; Erythrocytes* ; Humans ; Psoriasis*

Leprosy has two polar types. The one tuberculoid leprosy (TL) is characterized by well preserved cellular immunity with a good prognosia and the other lepromatous leprosy(LL) shows no cellular immunity with a poor prognosis. The preaent study was designed to measure the activity of adenosine deaminase (ADA) in sera and erythrocytes of leprosy patients, as it's activities are known to be decreased in immune deficiency diseases. There were no significant differences in the erythrocyte ADA activities among normal subjects(9. 60+4. 43 units/1012 cells), TL patients (7. 12+2. 51 units/1012 cells) and LL patients(6. 96+0. 81 units/1012 cells), The ADA activities in sera of TL patients(20.15+2. 90 units/L) did not differ from those of normal subjects(20.44+ 2. 07 units/L), but the LL patients(17. 52+3. 30 units/L) showed a slightly lowered activity than those of normal subjects.
Adenosine Deaminase* ; Adenosine* ; Deficiency Diseases ; Erythrocytes* ; Humans ; Immunity, Cellular ; Leprosy* ; Leprosy, Tuberculoid ; Prognosis