Impaired deoxyribonuclease activity in monoglandular and polyglandular autoimmunity.
OBJECTIVE
The enzyme desoxyribonuclease (DNase) degrades DNA during early apoptosis. Impaired DNase activity might increase susceptibility to autoimmune diseases. This study examined for the first time DNase activity in endocrine autoimmunity.


METHODS
Included were 112 patients with monoglandular (MGA) or polyglandular autoimmunity (PGA), their 93 healthy relatives, and 41 healthy controls. Serum DNase activity was quantified with a solid phase enzyme immunometric assay comprising degradation of the specific immobilized DNase substrate, formation of enzyme conjugate complexes using horseradish peroxidase conjugate solution, and enzymatic colour reaction.


RESULTS
The Bland-Altman plot of the interassay differences suggested good reproducibility (n=96). Compared to healthy controls (median 9.8, range 5.2-16.7 ng/ml), DNase activity was markedly lowered in patients with endocrine autoimmunity (5.8, 2.6-26.2 ng/ml; p<0.0001). Corresponding values in the following MGA, PGA, and relatives groups were 4.8 (2.8-19.0) ng/ml, 7.9 (2.6-26.2) ng/ml, and 8.4 (1.5-19.0) ng/ml, respectively. When MGA patients were splitted up by disease, patients with type 1 diabetes had the lowest DNase activity (3.6, 3.2-3.9 ng/ml) which positively correlated with HbA1c in females (r=0.486, p=0.041). Pathological reduction of DNase activity (below 5 ng/ml) was noted in 54%, 31%, 24%, and 0% of MGA, PGA, relatives, and controls, respectively. Anti-ds-DNA and anti-nucleosome antibodies were negative in the patients with MGA and PGA.


CONCLUSIONS
These findings indicate the potential relevance of DNase activity in patients with monoglandular and polyglandular autoimmunity and their clinically healthy relatives. The impaired DNase activity might reduce removal of circulating self- or pathogen-derived DNA thereby favoring autoimmune mechanisms by Toll-like receptor 9 co-activation.
Dittmar
M
M
Department of Medicine I, Gutenberg University, Mainz, Germany.
Poppe
R
R
Bischofs
C
C
Fredenhagen
G
G
Kanitz
M
M
Kahaly
G J
GJ
D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology; D004247:DNA / Q000097:blood / Q000276:immunology; D003851:Deoxyribonucleases / Q000097:blood* / Q000276:immunology; D004700:Endocrine System Diseases / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D051217:Toll-Like Receptor 9 / Q000276:immunology
C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA; D003851:Deoxyribonucleases