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    Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus
    (Springer Wien, 2023) Onmaz, Duygu Eryavuz; Tezcan, Dilek; Yilmaz, Sema; Onmaz, Mustafa; Unlu, Ali
    Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by increased release of proinflammatory cytokines that are known to activate the indoleamine 2,3-dioxygenase (IDO-1) enzyme, which catalyzes the rate-limiting step of the kynurenine pathway (KP). This study aimed to measure KP metabolite levels in patients with SLE and investigate the relationship between disease activity, clinical findings, and KP. The study included 100 patients with SLE and 100 healthy controls. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QA) concentrations were measured with tandem mass spectrometry. Serum KYN, KYNA, 3HAA, 3HK, and QA levels of the patients with SLE were significantly higher than the control group. Serum QA levels were elevated in patients with neurological involvement (four patients with peripheral neuropathy and two patients with mononeuropathy), serum KYN levels and KYN/TRP ratio increased in patients with joint involvement, and serum KYN, 3HK, and 3HAA levels and the KYN/TRP ratio were increased in patients with renal involvement. Moreover, KYN and KYN/TRP ratios were positively correlated with the disease activity score. These findings indicated that imbalances in KP metabolites may be associated with the pathogenesis, activation, and clinical manifestations of SLE.
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    Effects of hydroxychloroquine and its metabolites in patients with connective tissue diseases
    (Springer Basel Ag, 2021) Onmaz, Duygu Eryavuz; Tezcan, Dilek; Abusoglu, Sedat; Yilmaz, Sema; Yerlikaya, Fatma Humeyra; Onmaz, Mustafa; Abusoglu, Gulsum
    Hydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.
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    Elevated levels of neopterin and pentraxin 3 in patients with rheumatoid arthritis
    (Walter De Gruyter Gmbh, 2021) Ekin, Sabri; Sivrikaya, Abdullah; Akdag, Turan; Yilmaz, Sema; Gulcemal, Semral
    Objectives: As a systemic inflammatory disease, rheu-matoid arthritis (RA) is the most common inflammatory arthritis in the population and there is no specific diag-nostic marker in laboratory tests. The purpose of the study was to determine whether serum neopterin and pentraxin 3 (PTX3) levels may be a marker of increased inflammation in RA patients. Materials and methods: The study were consist of 30 RA patients and 30 healthy controls who were admitted to the department of rheumatology. Blood specimens were taken from both group, and the levels of neopterin were analyzed by chromatography method (HPLC) and the PTX 3 levels were measured by enzyme-linked immunosorbent assay (ELISA). All data and demographic characteristics of par-ticipants were also recorded. Results: Serum neopterin and PTX 3 levels of the patient group (25.99 +/- 7.24 ng/mL and 4.19 +/- 1.01 ng/dL, respec-tively) was higher than the control group (9.55 +/- 0.74 ng/mL and 2.23 +/- 0.39 ng/dL, respectively). These results were remarkable significant (p<0.01). No statistically significant correlation was found between age-PTX 3, age-neopterin and PTX 3-neopterin parameters in the patient group. In the control group, a significant negative correlation was found between age and PTX 3 (p<0.05), and a positive correlation between neopterin and PTX 3. Conclusions: Consequently, the serum neopterin and PTX 3 levels were higher in RA patients as compared to the healthy individuals. Our study suggest that there is a relation between neopterin and PTX 3 levels with RA patients. These findings suggest that neopterin and PTX 3 are important markers in the monitoring of RA disease.
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    Elevated levels of neopterin and pentraxin 3 in patients with rheumatoid arthritis
    (Walter De Gruyter Gmbh, 2021) Ekin, Sabri; Sivrikaya, Abdullah; Akdag, Turan; Yilmaz, Sema; Gulcemal, Semral
    Objectives: As a systemic inflammatory disease, rheu-matoid arthritis (RA) is the most common inflammatory arthritis in the population and there is no specific diag-nostic marker in laboratory tests. The purpose of the study was to determine whether serum neopterin and pentraxin 3 (PTX3) levels may be a marker of increased inflammation in RA patients. Materials and methods: The study were consist of 30 RA patients and 30 healthy controls who were admitted to the department of rheumatology. Blood specimens were taken from both group, and the levels of neopterin were analyzed by chromatography method (HPLC) and the PTX 3 levels were measured by enzyme-linked immunosorbent assay (ELISA). All data and demographic characteristics of par-ticipants were also recorded. Results: Serum neopterin and PTX 3 levels of the patient group (25.99 +/- 7.24 ng/mL and 4.19 +/- 1.01 ng/dL, respec-tively) was higher than the control group (9.55 +/- 0.74 ng/mL and 2.23 +/- 0.39 ng/dL, respectively). These results were remarkable significant (p<0.01). No statistically significant correlation was found between age-PTX 3, age-neopterin and PTX 3-neopterin parameters in the patient group. In the control group, a significant negative correlation was found between age and PTX 3 (p<0.05), and a positive correlation between neopterin and PTX 3. Conclusions: Consequently, the serum neopterin and PTX 3 levels were higher in RA patients as compared to the healthy individuals. Our study suggest that there is a relation between neopterin and PTX 3 levels with RA patients. These findings suggest that neopterin and PTX 3 are important markers in the monitoring of RA disease.
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    Evaluation of diagnostic performance of haematological parameters in Behcet's disease
    (Wiley-Hindawi, 2021) Tezcan, Dilek; Korez, Muslu Kazim; Gulcemal, Semral; Hakbilen, Selda; Akdag, Turan; Yilmaz, Sema
    Objective Behcet's Disease (BD) is a polygenic and chronic autoinflammatory multisystemic vasculitis disease characterised by mucocutaneous, musculoskeletal, neurological, gastrointestinal and ophthalmologic lesions. There has been no specific test or serum marker to measure and determine the diagnosis and severity of BD. Purpose The study aimed to investigate the diagnostic performance of haematological parameters as MLR (monocyte to lymphocyte ratio), NLR (neutrophil to lymphocyte ratio), PLR (platelet to lymphocyte ratio), MPV (mean platelet volume), MPVPR (mean platelet volume to platelet ratio), LMR (lymphocyte to monocyte ratio), LPM (lymphocyte and platelet multiplication), WLP (lymphocyte and leukocyte multiplication), RDW (red blood cell distribution width) and PCT (plateletcrit) in BD and compare these with disease activity and clinical findings. Methods A total of 266 participants (49 healthy control and 217 BD patients) were recruited from the rheumatology department in a single-centre as a case-control study. The laboratory data were obtained from the electronic registration database. BD Activity scores (BDCAF/Behcet's Disease Current Activity Form) were calculated. Laboratory findings of BD patients and healthy controls were compared and evaluated. Results RDW, Platelet, PCT, NLR and PLR values were significantly higher in patient group than in the healthy controls. However, haemoglobin, MPVPR and LMR were significantly lower in the patient group which compared with the healthy controls. LPM in BD with genital ulcers, WLP in BD with genital ulcers and arthritis, MPR in BD with uveitis, RDW in BD with thrombosis and neuro-Behcet's disease (NBD), PLR in NBD were observed to be higher. However, LMR in NBD and MPV in BD with thrombosis were lower than those without. There was a positive correlation between BDCAF score and RDW, and NLR. Conclusion Haemoglobin, RDW, Platelet, PCT, NLR, LMR, PLR and MPVPR were statistically significant predictors for BD. RDW, PCT and NLR are the most valuable predictors for BD.