Mirjana Gajic-Veljic1, Branka Bonaci-Nikolic2, Branislav Lekic3, Dusan Skiljevic4, Jasmina Ciric5, Svetlana Zoric6, Biljana Stojimirovic7, Milos Nikolic1. 1. Faculty of Medicine, University of Belgrade, Clinic of Dermatovenereology, milos.nikolic@med.bg.ac.rs. 2. Faculty of Medicine, University of Belgrade, Clinic of Allergy and Clinical Immunology. 3. Clinic of Dermatovenereology. 4. Faculty of Medicine, University of Belgrade, Clinic of Dermatovenereology. 5. Faculty of Medicine, University of Belgrade, Clinic of Endocrinology and. 6. Clinic of Endocrinology and. 7. Faculty of Medicine, University of Belgrade, Clinic of Nephrology, Clinical Center of Serbia, Belgrade, Serbia.
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. CONCLUSION: 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.
OBJECTIVE: To study the role of deoxyribonuclease (DNase) I activity and ANCA in propylthiouracil (PTU)-induced lupus-like syndrome (LLS). METHODS: We compared 36 SLEpatients with 17 PTU-induced LLSpatients 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 LLSpatients were serologically and clinically followed for 4.1 (S.D. 2.0) years. RESULTS:PTU-induced LLSpatients less frequently had arthritis, renal and neurological manifestations, but more frequently had fever, purpura, urticarial-like vasculitis and ulceration (P < 0.01). PTU-induced LLSpatients more frequently had polyspecific ANCA (anti-MPO, anti-elastase and anti-PR3 were most commonly detected) (P < 0.01). SLEpatients more frequently had anti-dsDNA, anti-ENA, anti-nucleosome, anti-C1q (P < 0.01) and anti-histone antibodies (P < 0.05). PTU-induced LLSpatients had lower DNase I activity than SLEpatients 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. CONCLUSION: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.