Anti-adenosine deaminase antibodies in lupus erythematosus

Abstract

Adenosine deaminase (ADA) is an enzyme involved in purine metabolism and has a major role in the development and function of lymphoid cells. Congenital deficiency of ADA results in severe immunodeficiency. Patients with congenital ADA deficiency treated with polyethylene glycol-conjugated bovine ADA develop antibodies to ADA. This leads us to investigate the role of anti-ADA antibodies in patients with systemic rheumatic diseases. Commercially available ADA was used in ELISA and immunoblots for detection of anti-ADA antibodies. Four out of 100 patients examined were positive for anti-ADA antibodies. Two of them had peripheral blood lymphopenia but the antibody levels did not appear to correlate with the lymphocyte counts. Immunoblotting revealed that the antibodies recognized a 40 kDa peptide of ADA, corresponding to ADA1, the major component of ADA. Affinity-purified antibodies were used to locate the distribution of ADA on Hep-2 cells and lymphocytes by indirect immunofluorescence. Anti-ADA antibodies gave a distinct nuclear speckled pattern on acetone-fixed cells. With viable cell immunofluorescence, anti-ADA antibodies also stained the cell surface of HEp-2 cells and lymphocytes, indicating surface expression of ADA. The anti-ADA antibodies failed to gain access into the cytoplasm or nuclei when added to the cultures of HEp-2 cells. In summary, this is the first report of detection of anti-ADA1 autoantibody which is a new type of ANA with discrete, speckled nuclear staining, but which may not be associated with lymphopenia.

Increasing Importance of Stem Cell Gene Therapy in Adenosine Deaminase Deficiency?

“…Thrombocytosis, autoantibody development, and immune dysregulation were reported to be complications as seen in this patient (1,3,6,10,15). Development of anti-ADA autoantibody, a new type of antinuclear antibody with discrete speckled nuclear staining, may be part of autoimmune process during this therapy and recently also demonstrated in 4/100 lupus patients (13). Decreased thymic function, B-cell oligoclonality, and increased spontaneous apoptosis contributing this immune dysregulation and autoimmune phenomena were also found to be associated with PEG-ADA therapy (14).…”

Specific increase in enzymatic activity of adenosine deaminase 1 in rheumatoid synovial fibroblasts

“…It also seems possible that the apparently higher deaminase activity in RA FLS reflects an abundance of ecto‐ADA bound to RA FLS via CD26 and/or A 1 receptors. In fact, RA FLS express all 4 adenosine receptors, including A 1 receptor (40), and the ecto‐ADA from HEp‐2 cells and from lymphocytes obtained from patients with chronic lymphocytic leukemia was identified as ADA1 (41). To further address the question of whether the increased ADA1 activity is an intrinsic characteristic of RA FLS, we compared levels of ADA gene expression in RA FLS and OA FLS.…”