title: Possible impact of plasma RNase activity on immune dysfunction in juvenile diabetes mellitus.
abstract: OBJECTIVE
  The ribonuclease (RNase) family represents important enzymes used widely in biomedical and biotechnological applications, as well as for diagnostic and therapeutic purposes. This study was undertaken to test the possibility that plasma alkaline RNase (free or inhibitory bound) determination may be useful in studying the dysregulation of nucleic acid and oligonucleotide metabolism as a possible pathogenetic mechanism in development of immune dysfunction in juvenile diabetes mellitus.
  
  
  METHODS
  Children with type 1 diabetes (n=32, age group of 5--14 yr), together with age-matched control subjects (n=35), were enrolled in the study. None had microvascular complications. According to the metabolic regulation of the disease and the hemoglobin A1c (HbA1c) level, all patients were divided into two groups (HbA1c<7.5% and HbA1c>7.5%). According to the duration of diabetes, diabetic children were divided into two groups: duration of diabetes less than 1 yr and duration of diabetes greater than 1 yr. The control group consisted of age-matched subjects (n=35; 15 girls and 20 boys) who were clinically healthy. The activity of free and inhibitory-bound RNase and the level of acid soluble nucleotides were measured in heparinized plasma.
  
  
  RESULTS
  The inhibitory-bound enzyme activity was higher in diabetic children, followed by sharply decreased free enzyme, especially in the group with the level of HbA1c above 7.5%. Recent-onset diabetic patients had lower free RNase activity compared with those with longer duration of the disease. The amount of pre-existing acid-soluble oligonucleotides was significantly increased in diabetic children, especially in those with poor metabolic control.
  
  
  CONCLUSIONS
  Our observed preliminary results may suggest a hypothesis that a persistent increase of oligonucleotide fragments, most probably due to insufficient RNase activity, may lead to T-cell hyperactivity in type 1 diabetes through the activation of toll-like receptors (TLRs). The measurement of RNase(s) activity (free, inhibitory-bound, or specific toward different substrates), together with the well-known immunobiochemical parameters of diabetes, may help further efforts in identifying a disease-specific early biological marker of immunity dysfunction in juvenile diabetes.
authors.affiliation: Institute of Biochemistry, Clinic of Pediatrics, Institute of Chemistry and Clinic for Endocrinology, Medical Faculty University of Nis, Serbia and Montenegro.
authors.forename: Gordana
authors.initials: G
authors.lastname: Kocic
authors.forename: Gordana
authors.initials: G
authors.lastname: Bjelakovic
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Saranac
authors.forename: Sasa
authors.initials: S
authors.lastname: Zivic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Jevtovic
authors.forename: Dusan
authors.initials: D
authors.lastname: Sokolovic
authors.forename: Dusica
authors.initials: D
authors.lastname: Pavlovic
authors.forename: Radmila
authors.initials: R
authors.lastname: Pavlovic
authors.forename: Radivoj
authors.initials: R
authors.lastname: Kocic
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D012260:Ribonucleases / Q000097:blood*; D013997:Time Factors; D051193:Toll-Like Receptors
chemical_list: D006442:Glycated Hemoglobin; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D012260:Ribonucleases; D051193:Toll-Like Receptors