Can Pentraxin-3 be a candidate marker in the follow-up of the patients with Behcet's disease?
PATIENTS AND METHODS
Forty-two BD patients (15 males, 27 females; mean age 39.7 [+ or -] 8.6 years; range 20 to 64 years), who attended Rheumatology Clinic at the Department of Internal Medicine, Medeniyet University Goztepe Training and Research Hospital between January 2011 and June 2011 and were diagnosed according to the International Study Group of BD, 13 and 42 healthy controls (14 males, 28 females; mean age 40.8 [+ or -] 8.2 year; range 25 to 60 years) were included. Exclusion criteria were disorders and habits that may affect inflammatory state (i.e. diabetes mellitus, dyslipidemia, malignancy, other rheumatologic or inflammatory disease, alcohol consumption, smoking, drug use). The present study was approved by the Ethical Board (01.04.2011 dated, decision no: 11/C) and written informed consent was obtained from all patients. The study was conducted in accordance with the principles of the Declaration of Helsinki. Morning blood samples were taken after an overnight fasting. Blood samples were centrifuged at 1,500 g for 10 minutes at room temperature within two hours after collection. Serum CRP was measured by nephelometric method (Immage[R] Immunochemistry System, Beckman Coulter, USA) as a part of daily clinical practice. Plasma (ethylenediaminetetraacetic acid-anticoagulated) samples were stored at -200 [degrees]C until analysis. Plasma PTX-3 concentration was measured by using the commercially available enzyme-linked immunosorbent assay kit (Quantikine Human Pentraxin 3/TSG-14 Immunoassay, R&D Systems, Minneapolis, USA). The analytic sensitivity of the test was 0.025 ng/mL, and the intra-assay variation coefficient (CV %) for the three separate concentrations were 3.8 (mean value: 2.61 [+ or -] 0.01, n=20), 3.7 (mean value: 7.72 [+ or -] 0.28, n=20), and 4.4 (mean value: 14.1 [+ or -] 0.62, n=20)
The data were expressed as mean [+ or -] standard deviation (SD) or mean [+ or -] standard error of the mean (SEM). Statistical analysis was performed using SPSS version 16.0 for Windows (SPSS Inc., Chicago, IL, USA). Comparison between the groups were made with unpaired t-test and Mann-Whitney U test, as appropriate. Correlations were performed by the Spearman rank test. The clinical performance of CRP and PTX-3 were assessed using receiver operating characteristics curves and calculated likelihood ratios for two cut-points with either high sensitivity or high specificity. A p value of <0.05 was considered to be statistically significant.
All the patients with BD were under treatment and their clinical data can be seen in Table 1. Both CRP and PTX-3 levels were significantly higher among patients with BD than healthy controls (0.71 [+ or -] 0.13 vs 0.27 [+ or -] 0.03, p<0.001 for CRP and 1.33 [+ or -] 0.29 vs 0.85 [+ or -] 0.12, p<0.05 for PTX-3; respectively) (Table 2). Nevertheless, increases in PTX-3 and CRP levels were similar (area under the curve: 0.633 [+ or -] 0.062 vs 0.729 [+ or -] 0.05; respectively) (Figure 1). Subgroup analyses were performed according to clinical features of BD. Mean PTX-3 and CRP levels were 1.1 vs 1.5, p=0.5; 0.5 vs 0.9, p=0.5; respectively, in patients with mucocutaneous involvement alone and with other involvements; whereas they were 0.9 vs 1.6, p=0.1; 0.5 vs 0.8, p=0.3; respectively, in patients with and without peripheral arthritis; and 1.7 vs 0.9, p=0.06; 1.0 vs 0.5, p=0.07; respectively, in patients with and without uveitis (Table 3).
In the present study, we determined that PTXs, both CRP and PTX-3, which are inflammation markers, were significantly higher in patients with BD. Nevertheless, specificity and sensitivity of PTX-3, which is a novel long PTX, were similar to those of CRP. In previous studies, it was hypothesized that PTX-3, unlike CRP, may be a rapid marker for primary local activation of innate immunity and inflammation and an indicator of disease activity while in other studies, correlation between levels of PTX-3 and CRP was found to be weak. [14-17] In this study, PTX-3, similar to CRP, was found to be associated with BD but did not show any superiority when compared to CRP. There are limited number of studies investigating PTX-3 levels in rheumatologic diseases. In a study investigating whether PTX-3 is an indicator of small vessel vasculitis activity  in patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis, systemic lupus erythematosus, rheumatoid arthritis, and CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia), PTX-3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (p<0.005). Different from our study, PTX-3 levels did not correlate with CRP levels in patients with vasculitis. 
In another study conducted on patients with rheumatoid arthritis, it was shown that PTX-3, unlike CRP, contributed to the complement-mediated mechanism causing inflammation and tissue damage. Increased levels of PTX-3 protein was obtained in synovial fluids from patients with rheumatoid arthritis. In contrast to other acute phase reactants, the majority of PTX-3 synthesis is extrahepatic and in that study the main source of PTX-3 was the synovial pannus. 
A study in patients with psoriatic arthritis showed a positive correlation between PTX-3 and disease activity of psoriasis. A strong PTX-3 staining in fibroblasts, endothelial cells and monocytes/macrophages was detected in severe psoriatic skin lesions. 
Recently, in a Turkish cohort of BD patients similar to our study group,  it was determined that PTX-3 levels did not correlate with CRP or with any domains of BD's current activity form in contrast to our present study. In our study, PTX-3 levels were found to be significantly higher in patients with BD. Since most of the patients of our cohort were in remission, we tried to find out the difference of PTX-3 levels according to BD's site-specific involvement, rather than disease activity. PTX-3 levels did not show any difference according to involvement. We only observed a slight increase in patients who had uveitis. However, this increase was not statistically significant. Our study indicates that PTX-3 can be an alternative parameter to CRP in the follow-up of BD. However, we need further studies to determine the relationship between PTX-3 and severity of BD.
Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.
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Banu ALPASLAN MESCI, (1) Banu ISBILEN BASOK, (2) Hatice GUL SAGUN, (1) Gokhan GONENLI, (1) Mukaddes KAVALA, (3) Esen KASAPOGLU GUNAL, (4) Esra EKIZ, (5) Ferruh ISMAN, (2) Aytekin OGUZ (1)
(1) Department of Internal Medicine, Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey
(2) Department of Biochemistry, Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey
(3) Department of Dermatology, Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey
(4) Department of Rheumatology, Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey
(5) Department of Internal Medicine, Esenler Women's & Children Hospital, Istanbul, Turkey
Received: July 04, 2016 Accepted: August 01, 2016 Published online: December 15, 2016
Correspondence: Esra Ekiz, MD. Esenler Kadin Dogum ve Cocuk Hastaliklari Hastanesi, lc Hastaliklari Klinigi, 34230 Esenler, Istanbul, Turkey.
Tel: +90 212-440 39 00 e-mail: firstname.lastname@example.org
Caption: Figure 1. Sensitivities of C-reactive protein and Pentraxin-3.
Table 1. Laboratory findings of patients with Behget's disease Values Normal range Hemoglobin (g/dL) 10.7 11.7-15.5 Hematocrit (%) 32.4 37-44 Leukocyte count (mcrL) 9.24 3.800-11.000 Platelet (mcrL) 291.000 150.000-350.000 Erythrocyte sedimentation rate 9 0-20 (mm/h) C-reactive protein (mg/L) 0.72 0-6 Urea (g/dL) 119 13-43 Creatinine (mg/dL) 1.48 0.7-1.3 Rheumatoid factor (IU/mL) 14.0 0-18 Anti-CCP (unit/mL) 0.6 0-2.5 ANA 1:>1000 granular Negative pattern Anti-SSA ++ Positive Negative Anti-SSB +++ Positive Negative Ro-52 (52 Kda) +++ Positive Negative ANCA Negative Negative Anticardiolipin IgM/IgG Negative Negative Venereal disease research-RPR Negative Negative test Complement component 4 (C4) 22.9 15-50 (mg/dL) Double-stranded DNA (dsDNA) Negative Negative antibody Direct Coombs test (IgG) ++++ Positive Negative Anti-CCP: Anti-cyclic citrullinated peptide; ANA: Antinuclear antibody; Anti-SSA: Anti Sjogren syndrome A; Anti-SSB: Anti Sjogren syndrome A; ANCA: Anti-neutrophil cytoplasmic antibody; RPR: Rapid plasma regain; dsDNA: Double stranded Deoxyribonucleic acid; IgG: Immunoglobulin G. Table 2. Comparison of inflammatory markers between two study groups Healthy controls (n=42) n Mean [+ or -] SD Mean [+ or -] SEM Gender Males 14 Females 28 C-reactive protein 0.27 [+ or -] 0.03 (mg/dL) Erythrocyte 20.1 [+ or -] 11.0 sedimentation rate (mm/hr) Pentraxin-3 (ng/mL) 0.85 [+ or -] 0.12 Patients with BD (42) n Mean [+ or -] SD Mean [+ or -] SEM Gender Males 15 Females 27 C-reactive protein 0.71 [+ or -] 0.13 (mg/dL) Erythrocyte 24.3 [+ or -] 16.5 sedimentation rate (mm/hr) Pentraxin-3 (ng/mL) 1.33 [+ or -] 0.29 P Gender Males Females C-reactive protein <0.001 (mg/dL) Erythrocyte >0.05 sedimentation rate (mm/hr) Pentraxin-3 (ng/mL) <0.05 SD: Standard deviation; SEM: Standard error of mean. Table 3. Comparison of pentraxin-3, C-reactive protein and erythrocyte sedimentation rate levels with regards to sites of involvement in patient group Pentraxin-3 P With only mucocutaneus (n=18) vs 1 vs 1.5 0.5 with other involvement (n=26) With uveitis (n=18) vs without 1.7 vs 0.9 0.06 uveitis (n=21) With peripheral arthritis (n=15) vs 0.9 vs 1.6 0.1 without peripheral arthritis (n=22) CRP P With only mucocutaneus (n=18) vs 0.5 vs 0.9 0.59 with other involvement (n=26) With uveitis (n=18) vs without 1.0 vs 0.5 0.07 uveitis (n=21) With peripheral arthritis (n=15) vs 0.5 vs 0.8 0.3 without peripheral arthritis (n=22) ESR P With only mucocutaneus (n=18) vs 20 vs 27 0.5 with other involvement (n=26) With uveitis (n=18) vs without 29 vs 19 0.07 uveitis (n=21) With peripheral arthritis (n=15) vs 24 vs 25 0.3 without peripheral arthritis (n=22) CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate.
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|Title Annotation:||ORIGINAL ARTICLE|
|Author:||Mesci, Banu Alpaslan; Basok, Banu Isbilen; Sagun, Hatice Gul; Gonenli, Gokhan; Kavala, Mukaddes; Gun|
|Publication:||Turkish Journal of Rheumatology|
|Date:||Jun 1, 2017|
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