Polyclonal Antibodies from Blood and Cerebrospinal Fluid of Patients with Multiple Sclerosis Effectively Hydrolyze DNA and RNA

A. G. Baranovskii¹, T. G. Kanyshkova¹, A. S. Mogelnitskii², V. A. Naumov², V. N. Buneva¹, E. I. Gusev³, A. N. Boiko³, T. A. Zargarova⁴, O. O. Favorova³, and G. A. Nevinsky^1*

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

²Army Hospital No. 333, ul. Voinskaya 24, Novosibirsk, 630017 Russia

³Russian State Medical University, Ministry of Public Health of Russian Federation, ul. Ostrovityanova 1, Moscow, 117437 Russia; fax: (095) 414-6699; E-mail: favorov@imb.imb.ac.ru

⁴Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, 142292 Russia; fax: (27) 790-527; E-mail: root@ev.people.serpukhov.su

^* To whom correspondence should be addressed.

Received March 24, 1998; Revision received June 20, 1998

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It is known that in the blood of patients with some autoimmune diseases catalytically active antibodies hydrolyzing proteins, DNA, and RNA may be detected. In the present work homogeneous preparations of IgG antibodies (Ab) possessing high affinity for nucleic acids (NA) were obtained for the first time from blood and cerebrospinal fluid of patients with multiple sclerosis (MS). The fraction of IgG Ab as well as its Fab fragments and isolated light chains of both kappa- and lambda-types were shown to catalyze effectively the hydrolysis of DNA and RNA. It is shown by different methods that the capability for nucleic acid hydrolysis is an intrinsic property of the polyclonal Ab. NA-hydrolyzing Ab were detected in the blood of 69 of 72 and in the cerebrospinal fluid of 5 of 5 examined MS patients, while they were not detected in the blood of any of 50 healthy donors examined. Comparison of relative rates of RNA hydrolysis and of the substrate specificity in hydrolysis of various model RNAs--cCMP, poly(U), poly(A), and poly(C)--revealed pronounced differences of MS antibodies from ribonucleases of human blood, ribonuclease A, and all earlier described abzymes. The abzymes are usually characterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS patients are the first example of autoabzymes whose specific activity in RNA hydrolysis is comparable or even higher than that of pancreatic ribonuclease A--one of the most active RNA-hydrolyzing enzymes.

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KEY WORDS: human subject, blood, cerebrospinal fluid, catalytically active antibodies, abzymes, multiple sclerosis, nucleases, RNA hydrolysis, DNA hydrolysis

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