title: Importance of low serum DNase I activity and polyspecific anti-neutrophil cytoplasmic antibodies in propylthiouracil-induced lupus-like syndrome.
abstract: OBJECTIVE
  To study the role of deoxyribonuclease (DNase) I activity and ANCA in propylthiouracil (PTU)-induced lupus-like syndrome (LLS).
  
  
  METHODS
  We compared 36 SLE patients with 17 PTU-induced LLS patients diagnosed from 2008 to 2014. We studied ANCA profile (MPO, PR3, lactoferrin, CTG, elastase, bactericidal/permeability-increasing protein), anti-dsDNA, anti-ENA, anti-nucleosome, anti-histone, anti-C1q, anti-aCL, complement components, cryoglobulins and serum DNase I activity. Healthy persons and patients without LLS treated with PTU comprised the control groups. Twelve LLS patients were serologically and clinically followed for 4.1 (S.D. 2.0) years.
  
  
  RESULTS
  PTU-induced LLS patients less frequently had arthritis, renal and neurological manifestations, but more frequently had fever, purpura, urticarial-like vasculitis and ulceration (P < 0.01). PTU-induced LLS patients more frequently had polyspecific ANCA (anti-MPO, anti-elastase and anti-PR3 were most commonly detected) (P < 0.01). SLE patients more frequently had anti-dsDNA, anti-ENA, anti-nucleosome, anti-C1q (P < 0.01) and anti-histone antibodies (P < 0.05). PTU-induced LLS patients had lower DNase I activity than SLE patients and controls (P < 0.01). Discontinuation of PTU increased DNase I activity, although it did not reach the levels of controls (P < 0.01). After remission, MPO-ANCA decreased (P < 0.01), but persisted for a long time.
  
  
  CONCLUSIONS
  PTU, as a trigger, and low DNase I activity, as a predisposing factor, may lead to LLS. Polyspecific ANCAs are useful markers for differentiating SLE from PTU-induced LLS. Low DNase I activity might be an important prognostic biomarker for PTU-induced LLS. Monitoring of ANCA and DNase I activity may prevent long-lasting exposure to causal drugs, unnecessary immunosuppressive therapy and severe complications of LLS.
authors.affiliation: Faculty of Medicine, University of Belgrade, Clinic of Dermatovenereology, milos.nikolic@med.bg.ac.rs.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Gajic-Veljic
authors.affiliation: Faculty of Medicine, University of Belgrade, Clinic of Allergy and Clinical Immunology.
authors.forename: Branka
authors.initials: B
authors.lastname: Bonaci-Nikolic
authors.affiliation: Clinic of Dermatovenereology.
authors.forename: Branislav
authors.initials: B
authors.lastname: Lekic
authors.affiliation: Faculty of Medicine, University of Belgrade, Clinic of Dermatovenereology.
authors.forename: Dusan
authors.initials: D
authors.lastname: Skiljevic
authors.affiliation: Faculty of Medicine, University of Belgrade, Clinic of Endocrinology and.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Ciric
authors.affiliation: Clinic of Endocrinology and.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Zoric
authors.affiliation: Faculty of Medicine, University of Belgrade, Clinic of Nephrology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Stojimirovic
authors.affiliation: Faculty of Medicine, University of Belgrade, Clinic of Dermatovenereology, milos.nikolic@med.bg.ac.rs.
authors.forename: Milos
authors.initials: M
authors.lastname: Nikolic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D013956:Antithyroid Agents / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003851:Deoxyribonucleases / Q000097:blood*; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D011441:Propylthiouracil / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D013577:Syndrome; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D013956:Antithyroid Agents; D015415:Biomarkers; D011441:Propylthiouracil; D003851:Deoxyribonucleases
keywords: anti-neutrophil cytoplasmic antibodies; deoxyribonuclease I (DNase I); lupus-like syndrome; propylthiouracil; systemic lupus erythematosus