Polyclonal antibodies from blood and cerebrospinal fluid of patients with multiple sclerosis effectively hydrolyze DNA and RNA

It is known that in the blood of patients with some autoimmune diseases cat alytically active antibodies hydrolyzing proteins, DNA, and RNA may be dete cted. In the present work homogeneous preparations of IgG antibodies (Ab) p ossessing 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 lig ht chains of both kappa- and lambda-types were shown to catalyze effectivel y 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 poly clonal 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 hydrol ysis of various model RNAs-cCMP, poly(U), poly(A), and poly(C)-revealed pro nounced differences of MS antibodies from ribonucleases of human blood, rib onuclease A, and all earlier described abzymes. The abzymes are usually cha racterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS pat ients are the first example of autoabzymes whose specific activity in RNA h ydrolysis is comparable or even higher than that of pancreatic ribonuclease A-one of the most active RNA-hydrolyzing enzymes.