DNA-Hydrolyzing Antibodies from Sera of Autoimmune-Prone MRL/MpJ-lpr Mice

V. V. Dubrovskaya¹, A. S. Andryushkova², I. A. Kuznetsova¹, L. B. Toporkova³, V. N. Buneva^1,2, I. A. Orlovskaya³, and G. A. Nevinsky^1,2*

¹Novosibirsk Institute of Bioorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, pr. Lavrent'eva 8, Novosibirsk 630090, Russia; fax: (3832) 333-677; E-mail: nevinsky@niboch.nsc.ru

²Novosibirsk State University, ul. Pirogova 2, Novosibirsk 630090, Russia

³Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, ul. Yadrentsovskaya 14, Novosibirsk 630099, Russia

^* To whom correspondence should be addressed.

Received May 13, 2003

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Catalytically active antibodies (abzymes) hydrolyzing proteins, polysaccharides, ATP, DNA, and RNA have been detected in the sera of patients with various autoimmune and some viral diseases, but abzymes from the sera of animals are practically unstudied. The development of lupus-like autoimmune disease of MRL/MpJ-lpr mice is an experimental model for study of autoimmune pathologies and immunopathogenesis. In this work, homogeneous IgG preparations were isolated from the sera of MRL/MpJ-lpr mice. These antibodies (Abs), their Fab-fragments, and isolated light chains were shown to possess catalytic activity in DNA hydrolysis, whereas Abs from the sera of control healthy mice did not hydrolyze DNA. The data demonstrate that DNA hydrolyzing activity is an intrinsic property of Abs from MRL/MpJ-lpr mice. It was shown that various markers of autoimmune pathologies (level of total protein concentration in urea (proteinuria), Abs titers to native and denatured DNA, and DNA-hydrolyzing activity of IgG) increased in animals with aging, but they noticeably increased (2-22 times) only after appearance of obvious indicators of pathology independently of age. The highest increase in proteinuria (25-fold), anti-DNA Abs titers (12-19-fold), and abzyme activity (120-fold) was found in mice after their immunization with DNA-protein complex.

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KEY WORDS: MRL/MpJ-lpr mice sera, immunoglobulins, native abzymes, DNA hydrolysis

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