Clin Rheumatol DOI 10.1007/s10067-014-2555-9
BRIEF REPORT
Serum amyloid-A in Behçet’s disease Antonio Vitale & Donato Rigante & Giuseppe Lopalco & Maria Giuseppina Brizi & Francesco Caso & Rossella Franceschini & Rosario Denaro & Mauro Galeazzi & Leonardo Punzi & Florenzo Iannone & Giovanni Lapadula & Antonella Simpatico & Edoardo Marrani & Luisa Costa & Rolando Cimaz & Luca Cantarini
Received: 4 February 2014 / Revised: 20 February 2014 / Accepted: 23 February 2014 # Clinical Rheumatology 2014
Abstract Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and previously investigated as a marker of disease activity in many rheumatologic disorders. Its significance in Behçet’s disease (BD), a chronic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes, is still unraveled. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. According to our findings, the occurrence of oral aphthosis, neurological impairment, and ocular disease is significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L, respectively. We also suggest that increased SAA levels might identify a thrombotic risk in BD with previous or concurrent vascular involvement. Keywords Disease activity . Homocysteine . Inflammation . Serum amyloid-A . Thrombosis . Uveitis Behçet’s disease (BD) is a chronic systemic inflammatory disorder at the crossroad between autoimmune and autoinflammatory
syndromes [1]. Unfortunately, there are no specific clues to assess BD disease activity. Erythrocyte sedimentation rate and C-reactive protein have resulted fruitless for this goal [1]. Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver under the stimulus of different proinflammatory cytokines, previously investigated as a potential laboratory marker of disease activity in many rheumatologic disorders [2–5]. In addition, SAA might disclose subclinical inflammation in patients affected with autoinflammatory disorders [6]. Few studies have evaluated the diagnostic value of SAA in BD [7]. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. During a 12-month follow-up period, 86 sequential blood samples were routinely collected from 26 Behçet’s disease (BD) patients who met the International Study Group diagnostic criteria for BD [8] every 3 to 4 months and/or at each disease relapse. Patients were included in the “active” group if they had at least two of the following BD-related clinical findings: oral aphthosis, genital ulcers, active uveitis, arthritides, vascular thrombosis/phlebitis, skin involvement, or
Antonio Vitale and Donato Rigante equally contributed to this work. A. Vitale : M. G. Brizi : F. Caso : M. Galeazzi : A. Simpatico : L. Cantarini (*) Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Siena, Italy e-mail: [email protected] D. Rigante Institute of Pediatrics, Università Cattolica Sacro Cuore, Rome, Italy G. Lopalco : F. Iannone : G. Lapadula Interdisciplinary Department of Medicine, Rheumatology Unit, Policlinico, Bari, Italy F. Caso : L. Punzi Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy
R. Franceschini : R. Denaro Ophthalmology and Neurosurgery Department, University of Siena, Siena, Italy
E. Marrani : R. Cimaz Department of Pediatrics, Rheumatology Unit, Anna Meyer Children’s Hospital, University of Florence, Florence, Italy
L. Costa Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Via S. Pansini 5, 80131 Naples, Italy
Clin Rheumatol Table 1 Demographic, laboratory, and general clinical characteristics of patients with Behçet’s disease recruited in our study Males, n (%) Age at first visit (mean±SD), in years Disease onset (mean±SD), in years Disease duration (mean±SD), in years HLA-B51 positivity, n (%) Serum amyloid-A levels, mean±SD (range), mg/L Homocysteine serum levels, mean±SD (range), μm/L Clinical features (%) Oral aphthosis Genital aphthosis Musculoskeletal involvement Peripheral nervous system involvement Central nervous system involvement Skin involvement Abdominal pain Vascular involvement
12 (46) 45.69±13.53 32.84±14.36 13.30±11.93 19 (73) 67.04±119.71 (1.54–759.2) 15.10±7.46 (6.5–49.6)
23/26 (84) 7/26 (27) 18/26 (69) 1/26 (4) 19/26 (73) 11/26 (42) 4/26 (15) 5/26 (19)
neurological manifestations. SAA levels were assayed by enzyme-linked immunosorbent assay in the 86 blood samples; homocysteine serum levels were also contextually measured. Statistical Package for Social Science (SPSS) package was used for statistical computations. Descriptive statistics was evaluated for sample size, mean, and standard deviation for quantitative variables. Nonparametric values were compared using the Fisher’s exact test to analyze 2×2 contingency Table 2 Frequencies of main clinical manifestations of Behçet’s disease referred to 86 sequential follow-up visits in 26 patients and Pearson’s correlation analysis (rho) between serum amyloid-A (SAA) and homocysteine serum levels, distinguishing any clinical manifestation. In the
tables. Different parametric values in the same groups were evaluated by Pearson’s correlation coefficients. A p value
BRIEF REPORT
Serum amyloid-A in Behçet’s disease Antonio Vitale & Donato Rigante & Giuseppe Lopalco & Maria Giuseppina Brizi & Francesco Caso & Rossella Franceschini & Rosario Denaro & Mauro Galeazzi & Leonardo Punzi & Florenzo Iannone & Giovanni Lapadula & Antonella Simpatico & Edoardo Marrani & Luisa Costa & Rolando Cimaz & Luca Cantarini
Received: 4 February 2014 / Revised: 20 February 2014 / Accepted: 23 February 2014 # Clinical Rheumatology 2014
Abstract Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and previously investigated as a marker of disease activity in many rheumatologic disorders. Its significance in Behçet’s disease (BD), a chronic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes, is still unraveled. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. According to our findings, the occurrence of oral aphthosis, neurological impairment, and ocular disease is significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L, respectively. We also suggest that increased SAA levels might identify a thrombotic risk in BD with previous or concurrent vascular involvement. Keywords Disease activity . Homocysteine . Inflammation . Serum amyloid-A . Thrombosis . Uveitis Behçet’s disease (BD) is a chronic systemic inflammatory disorder at the crossroad between autoimmune and autoinflammatory
syndromes [1]. Unfortunately, there are no specific clues to assess BD disease activity. Erythrocyte sedimentation rate and C-reactive protein have resulted fruitless for this goal [1]. Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver under the stimulus of different proinflammatory cytokines, previously investigated as a potential laboratory marker of disease activity in many rheumatologic disorders [2–5]. In addition, SAA might disclose subclinical inflammation in patients affected with autoinflammatory disorders [6]. Few studies have evaluated the diagnostic value of SAA in BD [7]. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. During a 12-month follow-up period, 86 sequential blood samples were routinely collected from 26 Behçet’s disease (BD) patients who met the International Study Group diagnostic criteria for BD [8] every 3 to 4 months and/or at each disease relapse. Patients were included in the “active” group if they had at least two of the following BD-related clinical findings: oral aphthosis, genital ulcers, active uveitis, arthritides, vascular thrombosis/phlebitis, skin involvement, or
Antonio Vitale and Donato Rigante equally contributed to this work. A. Vitale : M. G. Brizi : F. Caso : M. Galeazzi : A. Simpatico : L. Cantarini (*) Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Siena, Italy e-mail: [email protected] D. Rigante Institute of Pediatrics, Università Cattolica Sacro Cuore, Rome, Italy G. Lopalco : F. Iannone : G. Lapadula Interdisciplinary Department of Medicine, Rheumatology Unit, Policlinico, Bari, Italy F. Caso : L. Punzi Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy
R. Franceschini : R. Denaro Ophthalmology and Neurosurgery Department, University of Siena, Siena, Italy
E. Marrani : R. Cimaz Department of Pediatrics, Rheumatology Unit, Anna Meyer Children’s Hospital, University of Florence, Florence, Italy
L. Costa Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Via S. Pansini 5, 80131 Naples, Italy
Clin Rheumatol Table 1 Demographic, laboratory, and general clinical characteristics of patients with Behçet’s disease recruited in our study Males, n (%) Age at first visit (mean±SD), in years Disease onset (mean±SD), in years Disease duration (mean±SD), in years HLA-B51 positivity, n (%) Serum amyloid-A levels, mean±SD (range), mg/L Homocysteine serum levels, mean±SD (range), μm/L Clinical features (%) Oral aphthosis Genital aphthosis Musculoskeletal involvement Peripheral nervous system involvement Central nervous system involvement Skin involvement Abdominal pain Vascular involvement
12 (46) 45.69±13.53 32.84±14.36 13.30±11.93 19 (73) 67.04±119.71 (1.54–759.2) 15.10±7.46 (6.5–49.6)
23/26 (84) 7/26 (27) 18/26 (69) 1/26 (4) 19/26 (73) 11/26 (42) 4/26 (15) 5/26 (19)
neurological manifestations. SAA levels were assayed by enzyme-linked immunosorbent assay in the 86 blood samples; homocysteine serum levels were also contextually measured. Statistical Package for Social Science (SPSS) package was used for statistical computations. Descriptive statistics was evaluated for sample size, mean, and standard deviation for quantitative variables. Nonparametric values were compared using the Fisher’s exact test to analyze 2×2 contingency Table 2 Frequencies of main clinical manifestations of Behçet’s disease referred to 86 sequential follow-up visits in 26 patients and Pearson’s correlation analysis (rho) between serum amyloid-A (SAA) and homocysteine serum levels, distinguishing any clinical manifestation. In the
tables. Different parametric values in the same groups were evaluated by Pearson’s correlation coefficients. A p value
