The relationship of serum leptin levels with disease activity in Egyptian patients with rheumatoid arthritis

Aim of the workTo investigate whether serum leptin levels are elevated in patients with rheumatoid arthritis (RA) and whether these levels correlate with disease activity.Patients and methodsA case-control study was made on 37 patients with RA and 34 healthy control subjects. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts, disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analog scale (VAS) of pain and serum leptin concentrations.ResultsPatients with RA had mild to moderate (DAS28 < 5.1) disease activity. The mean serum leptin in patients with RA (12.15 ± 11.48 ng/mL) was significantly higher (p < 0.001) than controls (3.99 ± 1.84 ng/mL). Serum leptin levels were significantly (p < 0.001) higher in female RA patients than in female controls. A nonsignificant difference (p = 0.41) was found between male patients with RA and male controls. Serum leptin levels were significantly (p < 0.001) higher in women than in men in both patients and controls. Serum leptin levels did not show correlation with age, disease duration, duration of morning stiffness, VAS, number of swollen and tender joints, DAS28, HAQ, ESR or CRP in patients with RA. Serum leptin levels were correlated positively with BMI in RA patients. The BMI was significantly higher (p < 0.001) in female than in male patients with RA.ConclusionAlthough leptin levels were higher in RA patients, there was no correlation with disease activity parameters, therefore, leptin levels cannot be used to reflect disease activity.     

Sclerostin as an innovative insight towards understanding Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation leading to cartilage and local bone erosion. Sclerostin is a protein that in humans has been identified as an inhibitor of the pathway and leads to decreased bone formation.Aim of the workThis study aimed to investigate the level of serum sclerostin in RA patients, its association with inflammatory profile and its relation to disease activity and severity.Patients and methodsThirty-one Egyptian RA patients (28 females, 3 men) participated in this study. Their median age was 40 years. Disease activity score was assessed by the disease activity score (DAS28) and the functional status by the modified health assessment questionnaire (MHAQ). Ten matched controls were also included. Radiological severity was assessed according to the Larsen score. Serum sclerostin was measured.ResultsMedian serum sclerostin in RA patients was 2000 ng/dl (800–3300 ng/dl) which was significantly higher than in controls [210 ng/dl (150–2859)] (Z = −4.47, p < 0.001). Sclerostin significantly negatively correlated with C-reactive protein and DAS28 (p = 0.014 and p = 0.02 respectively) and positively correlated with the Larsen score and total joint count (p = 0.03 and p = 0.02 respectively). At serum level 267 ng/dl sclerostin has sensitivity of 96.8% to diagnose RA and a positive predictive value of 96.6%.ConclusionSerum sclerostin was significantly higher in RA patients than controls and correlated with disease activity and severity which highly suggests that it may play a role in the pathogenesis of RA making it a valuable new marker of monitoring the disease progress and prognosis.     

Clinical significance of soluble-triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with rheumatoid arthritis

Aim of the workTo assess serum concentrations of triggering receptor expressed on myeloid cells-1 (sTREM-1) in rheumatoid arthritis (RA) patients, and correlate them with the main clinical, serological, radiological features and functional capacity of RA patients.Patients and methodsSera from 61 RA patients, and 30 healthy controls were assayed for sTREM-1 by Enzyme Linked Immunosorbant Assay. RA disease activity was assessed using 28-joint disease activity score (DAS-28). Assessment of patient’s functional capacity was done using modified health assessment questionnaire (mHAQ). Standardized X-rays were done to all RA participants and evaluated according to Larsen scoreResultsSerum levels of sTREM-1 were significantly higher in RA patients vs healthy controls (57.61 ± 28.87 and 43.72 ± 10.64 ng/ml; p = 0.027). These levels were higher in patients with severe disease activity (68.27 ± 36.14 ng/ml) than those with mild and moderate disease activity (43.50 ± 6.49 ng/ml and 47.52 ± 12.26 ng/ml, respectively; p = 0.008). On the contrary, no significant difference was found in levels of sTREM-1 in patients with extra-articular involvement or positive RF than those without. Levels of sTREM-1 showed a highly significant positive correlation with DAS-28 (P = 0.001), ESR (P = 0.02) and mHAQ (p = 0.003).There were no significant correlations between sTREM-1 level with age, disease duration, morning stiffness, nor radiological narrowing and erosion scores.ConclusionLevels of sTREM-1 were elevated in RA patients and correlated significantly with clinical and laboratory markers of disease activity as well as functional disability (as determined by mHAQ). To confirm our results we propose that larger scale, multicenter studies with longer evaluation periods are needed.     

Insulin resistance as a risk factor for subclinical atherosclerosis in rheumatoid arthritis

BackgroundInsulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.Aim of the workTo study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.Patients and methodsForty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.ResultsRA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.ConclusionsIn RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.     

Influence of adipocytokines and IL-6 on ankylosing spondylitis disease activity and functional status

Aim of the workThis study aimed to assess serum levels of some adipocytokines (leptin, adiponectin and resistin) and IL-6 in patients with ankylosing spondylitis (AS) to evaluate their relationship to disease activity and functional capacity.Patient and methodTwenty-five AS patients were enrolled. Body mass index (BMI), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) and acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were assessed. Serum leptin, adiponectin, resistin and interleukin (IL)-6 levels were determined using enzyme-linked immunosorbent assay (ELISA).ResultsThe mean levels of leptin (9.1 ± 3.9 ng/ml), resistin (2.27 ± 1.15 ng/ml) and IL-6 (9.2 ± 5.8 pg/ml); were significantly elevated in patients with AS compared to the controls (p = 0.000, p = 0.0028 and p = 0.000, respectively). Only serum leptin levels correlated significantly with IL-6 (p = 0.004), and both serum leptin and IL-6 levels correlated significantly with BASDAI (p = 0.02 and p = 0.005, respectively), ESR (p = 0.04) and CRP (p = 0.01 and p = 0.006, respectively) in AS patients. Serum resistin did not correlate with any of the AS disease parameters, whereas, serum adiponectin neither significantly elevated nor correlated with any of these parameters.ConclusionThe associations of significantly increased levels of serum leptin and IL-6 with AS disease activity parameters give clues to their role in the inflammatory process of the disease. Failure to find any correlation between high serum resistin levels and AS disease activity parameters is suggestive of its role in the pathogenesis rather than disease activity.     

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in rheumatoid arthritis patients: Correlation with serum osteopontin levels and disease activity

BackgroundRheumatoid arthritis (RA) is a systemic, chronic inflammatory disease with genetic predisposition. Osteopontin (OPN) is overexpressed in RA and plays a key role in the perpetuation of synovitis. Not all RA patients show the same level of response to methotrexate (MTX) suggesting genetic variations in the drug-metabolizing enzymes.Aim of the workTo detect methylene-tetra-hydrofolate reductase (MTHFR) 677C/T and 1298A/C gene polymorphisms in RA patients treated with MTX and to investigate the relationship with serum OPN levels and disease activity.Patients and methods62 RA patients and 21 healthy controls were included. Serum OPN was measured using ELISA. Genotyping of MTHFR gene was carried out by polymerase chain reaction-restriction fragment length polymorphism. Disease activity score in 28 joints (DAS28) and the modified health assessment questionnaire (MHAQ) were assessed.ResultsThe patients’ age was 42.7 ± 12.7 years, F:M (4.6:1) and a disease duration of 5.7 ± 4.6 years. Their DAS28 was 4.1 ± 1.6 and the MHAQ (median 1; range 0–2.3). Serum OPN levels in RA patients (median 8.8; range 4–44.5 ng/ml) were significantly higher than in control (5.6; 2.1–10.9) (p = 0.002). In RA patients, serum OPN significantly correlated with the duration of morning stiffness (p = 0.009), ESR (p < 0.0001) and DAS28 (p < 0.0001). MTHFR (677C>T) polymorphisms significantly correlated with MHAQ (p = 0.012) while (1298A>C) polymorphisms significantly correlated with tender joint count (p = 0.04). OPN levels were higher among patients with MTHFR (1298A/C) AC genotype (8.9; 4.1–33.9 ng/ml), while in those with (677C>T) polymorphisms it was higher among those with CT genotype (8.9; 4.1–44.5).ConclusionSerum OPN level relates with the degree of rheumatoid activity.     

Serum level of interleukin-33 in rheumatoid arthritis patients and its association with bone erosion and interstitial lung disease

Aim of the workTo analyze the serum levels of IL-33 in RA patients and to investigate its relation to the clinical characteristics, laboratory investigations, joint erosions, functional status and disease activity. Its relation to the presence of interstitial lung disease (ILD) was well thought-out.Patients and methodsThe study included 50 RA patients and 30 matched control. Thorough clinical examination, investigations, disease activity score (DAS-28) and health assessment questionnaire (HAQ) were considered in the patients. Bone erosion was evaluated and interstitial lung disease (ILD) was identified on high-resolution computed tomography. The serum level of IL-33 was measured by enzyme-linked immunosorbent assay.ResultsSerum levels of IL-33 are significantly higher in RA patients (106.96 ± 52.6 pg/ml) than in healthy controls (46.9 ± 23 pg/ml) (p < 0.001). A significant correlation was found between IL-33 and the DAS28 (r = 0.4, p = 0.001), level of rheumatoid factor (r = 0.45, p = 0.001) and with the presence of ILD (r = 0.3, p = 0.04). There were no gender differences and the level did not significantly correlate with the age or disease duration. The medications received had no obvious effect on the IL-33 level. The level did not correlate with the HAQ. There was a significant correlation between the CT bone erosion scores the patient’s age, disease duration, rheumatoid nodules and DAS28. The erosion score also significantly correlated with the serum IL-33 levels in RA patients (r = 0.71, p = 0.001).ConclusionThese data support the hypothesis that IL-33 may be involved in RA pathogenesis and it may partly contribute to the bone erosion and ILD in RA patients.     

Sexual performance in rheumatoid arthritis patients – An unnoticed problem

Rheumatoid arthritis (RA) can influence sexual function due to several reasons, such as pain, restricted joint movements, fatigue, and problems with self-esteem and body image. It can affect serum androgen levels, which may be another cause of sexual dysfunction.Aim of the workTo compare between serum androgen levels in male patients with RA and normal males, and between the presence of erectile dysfunctions (EDs) in both groups.Patients and methodsThis study was performed on 42 individuals; 24 male patients suffering from RA and 18 healthy control male subjects. Patients were subjected to full history taking, full locomotor examination, and calculation of disease activity score, using 28 joint count (DAS-28). Assessment of serum dehydro-epiandrosterone sulfate (DHEA), total and free testosterone was done for all subjects. All subjects were asked to complete the Sexual Health Inventory for Men (SHIM).ResultsThere were highly statistically significant differences in the levels of serum DHEA, total and free testosterone levels between patients and controls (P < 0.001). Occurrence of EDs was more frequent in RA patients (45.8%) than in the control subjects (11.1%) and comparison between SHIM score of both groups revealed highly statistically significant differences (P < 0.001) with higher mean values in the control group.ConclusionErectile dysfunction is a prominent problem in male patients with RA. Assessment of sexual functions of RA males should be a part of routine assessment of disease status. Andrological consultation is recommended for a proper management of the condition.     

Serum leptin and osteoporosis in postmenopausal women with primary knee osteoarthritis

Aim of the workThe purpose of this study was to evaluate the relationship of serum leptin level and osteoporosis in postmenopausal women with knee osteoarthritis (KOA).Patients and methodsThe study included 40 postmenopausal women with primary KOA and 37 age-matched postmenopausal healthy controls. Plain X-ray knees were performed and assessed using the Kellgren–Lawrence (KL) grading scale. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry (DXA) in lumbar spine, hip and forearm regions. As a bone turn-over marker serum osteocalcin was measured. Serum leptin level was assessed in patients and control.ResultsThe mean age of the KOA patients was 58.05 ± 5.7 years. Osteoporosis was detected among 15% of the KOA patients and 35.1% of the control. The BMD was significantly increased at the spine and wrist in the patients than in the control (p = 0.011 and p = 0.015 respectively). The serum osteocalcin was comparable between patients (19.74 ± 8.05 ng/ml) and control (21.2 ± 8.36 ng/ml) (p = 0.5). Serum leptin was significantly higher in the patient (58.7 ± 27.17 ng/ml) compared to the control (48.75 ± 13.19 ng/ml) (p = 0.048), and significantly correlated with the degree of KOA (p = 0.017). No significant correlation was found between serum osteocalcin level or the BMD and the degree of KOA. There was a significant negative correlation between serum osteocalcin level and forearm BMD in KOA patients (r = −0.33, p = 0.038).ConclusionsAlthough postmenopausal women with KOA had significantly higher BMD, both diseases can coexist. It seemed that osteoarthritis does not prevent the occurrence of osteoporosis. Our study suggested a promising role of leptin as a biomarker of KOA.     

Evaluation of visfatin in patients with systemic lupus erythematosus: Correlation with disease activity and lupus nephritis

IntroductionRenal involvement affects about 50% of SLE patients accounting for significant morbidity and mortality in these patients. The adipokine “visfatin” acting as a growth factor for B-lymphocyte-precursors, exerts several proinflammatory functions. It was demonstrated as a marker of endothelial dysfunction (ED) in chronic kidney disease (CKD) thus could be a factor linking inflammation in SLE and kidney disease.Aim of the workTo assess serum visfatin level in SLE patients and its correlation to disease activity and lupus nephritis (LN) in these patients.Patients and methodsSerum level of visfatin using enzyme-linked immunosorbent assay (ELISA), chemical and immunological markers of SLE and LN were measured in 40 SLE patients and 40 age and sex matched healthy controls. Disease activity and renal involvement were assessed using SLE Disease Activity Index (SLEDAI) and Renal SLEDAI respectively further dividing patients into active versus inactive and LN versus non-LN respectively. Renal biopsies were taken from LN subgroup and were classified according to the modified WHO classification.ResultsA significantly higher serum visfatin level was found on comparing SLE patients (mean 109 ± 180 ng/ml, median18) with controls (mean 9.4 ± 11 ng/ml, median2.5) with statistically highly significant difference (z = 5.2, P < 0.001). Also there was a statistically significant difference as regards serum visfatin level between active SLE patients (mean 173 ± 111 ng/ml, median 14) and inactive patients (mean 139 ± 88 ng/ml, median 5) (z = 2.1, P < 0.05) as well as between patients with LN (mean 226 ± 180 ng/ml, median18) and patients with no LN (mean 101 ± 140 ng/ml, median 8(2-229)) (z = 2.1, P < 0.05). Visfatin had a highly significant positive correlation with disease duration (r = 0.48, P < 0.001), SLEDAI (r = 0.62, P < 0.001) as well as ESR, CRP and, renal score (r = 0.45, 0.35, and 0.65, respectively) while inverse correlation with estimated GFR (r = ?0.614) and C3 and C4 titre (r = ?0.26, r = ?0.35, respectively) was recorded. Visfatin showed high sensitivity in detecting active SLE and LN 83% and 85%, respectively.ConclusionSerum visfatin is strongly associated with LN in SLE patients and is a promising biomarker for prediction of renal involvement in these patients. It reflects SLE activity specially LN activity namely renal score and GFR decline. Further prospective studies are required to confirm visfatin as a destructive mediator of predictive and prognostic value in active lupus nephritis.     

Fatigue in rheumatoid arthritis and its relation to interleukin-6 serum level

Patients and methodsThe study included 30 patients with RA diagnosed according to the 2010 ACR-EULAR classification criteria for RA and 15 healthy controls. Patients were included if they were above 18 years and fulfilled a score ?6 over 10 of the 2010 ACR-EULAR classification criteria for RA. Disease activity was assessed using 28 joint disease activity score (DAS28), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP). Fatigue was assessed with the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) and serum IL-6 level was measured in patients and controls.ResultsThe BRAF-MDQ was significantly higher among patients (mean = 50.6 ± 15.2) than controls (mean = 7.8 ± 3.7) (p < 0.001). Patients’ mean IL-6 serum level was 35.05 ± 21.23 pg/ml and 4.72 ± 3.09 pg/ml among control subjects (p < 0.001). DAS 28 ranged between 4.33 and 7.67, mean 1st hour ESR was 43.57 mm and CRP was positive in 76.7% of patients. Significant correlations were found between BRAF-MDQ score and serum IL-6 level (r = 0.947, p < 0.001), ESR (r = 0.509, p < 0.001) as well as CRP positivity (r = 0.411, p = 0.005) in RA patients. Serum IL-6 level correlated with ESR (r = 0.463, p < 0.001) and CRP (r = 0.376, p = 0.01) among patients.ConclusionFatigue is a common symptom and scores higher among RA patients than healthy controls and should be measured in all RA patients with simple fatigue questionnaires matching with different cultures. Fatigue becomes more prominent as serum IL-6 level increases independently of the disease duration and activity.     

Assessment of synovitis in early rheumatoid arthritis by CXCL13 serum levels and power Doppler ultrasonography: Correlation with disease activity

Aim of the workAssessment of synovitis in rheumatoid arthritis (RA) is a major issue for proper treatment; it has been proven that high resolution ultrasound (US) examination could be of valuable help. The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. We aimed to find out the presence of synovitis in patients with recent-onset RA and its correlation with disease activity.Patients and methodsWe evaluated 30 patients with early RA for the presence and degree of synovitis by performing high resolution US and obtaining serum CXCL13 levels. In addition, we correlated these results with disease activity score 28 (DAS 28). Results of high resolution US and serum CXCL13 were also obtained for 20 healthy age- and sex-matched volunteers and served as controls.ResultsSerum CXCL13 level was significantly increased in early RA patients vs. controls (p < 0.001). High resolution US revealed that RA patients had a significant increased synovial thickness and high power Doppler US score. In RA patients, DAS 28 had a significant correlation with serum CXCL13 (r = 0.42, p = 0.02), synovial thickness (r = 0.39, p = 0.03) and power Doppler US score (r = 0.43, p = 0.02). Serum CXCL13 level correlated with synovial thickness (r = 0.63, p = 0.001) and power Doppler US score (r = 0.69, p = 0.001).ConclusionRecent-onset RA patients suffer from synovitis as evidenced by significantly increased serum CXCL13 and by high resolution US. Serum CXCL13 is a reliable marker of synovial inflammation which correlates better with synovial thickening and power Doppler US scores than DAS28.     

Serum 25-hydroxy vitamin D levels in Egyptian patients with rheumatoid arthritis: Association with disease activity,functional disability and radiological damage

Aim of the workThe aim of this study was to examine vitamin D (VD) levels and its associations with disease activity, functional disability and radiological damage in Egyptian patients with RA.Patients and methodsThis study included 150 RA patients and 150 matched controls. All participants were not receiving VD supplements. Serum 25(OH)-D levels were measured in all participants. Serum 25(OH)-D levels at 30 and 20 ng/ml were the cut-off values for VD insufficiency and deficiency, respectively. Associations of 25(OH)-D levels with disease activity score associated with C-reactive protein (DAS-28-CRP), functional disability assessed by the Health Assessment Questionnaire (HAQ) and radiological damage as assessed by the modified Larsen method were considered.ResultsLow VD levels were frequent in RA patients (22 ± 9.2 ng/ml) compared to the control (28.7 ± 9.6 ng/ml) (p < 0.001); 42.7% had VD levels <20 ng/ml and was <30 ng/ml in 80.7%. RA patients with VD deficiency were older, more frequently females and had higher swollen joint count (SJC), tender joint count, visual analogue scale for pain and DAS28-CRP. Only SJC and DAS28-CRP remained significant following the multivariate analysis (p = 0.029, p = 0.007 respectively), while rheumatoid factor, anti-cyclic citrullinated peptide antibodies, medications used, HAQ and radiologic score had no association with VD levels.ConclusionsVitamin D insufficiency and deficiency are common among Egyptian RA patients and are associated with decreased sun exposure. VD deficiency was related to older age, female gender, swollen joint count and disease activity. Vitamin D levels had no relation with RA functional disability and radiological damage.     

Expression of soluble sCD163 in serum of psoriatic patients is modulated by Goeckerman therapy

BackgroundCD163 is the monocyte/macrophage receptor for haptoglobin–haemoglobin complexes. The aim of this study was to assess the kinetics in the expression of CD163 on monocytes and the concentration of soluble sCD163 in serum of psoriatic patients in order to examine the effect of Goeckerman therapy.MethodssCD163 was measured in 71 patients before and after therapy, and in 57 healthy donors. A subgroup of 40 patients and 25 controls was used to assess the expression of membrane CD163. sCD163 was evaluated by ELISA. Flow cytometry method was used to determine the expression of membrane CD163 on monocytes, expressed as mean fluorescence index (MFI).ResultsBefore therapy, the serum level of sCD163 was significantly higher in our patients than in controls (P = 0.0154). However, we observed a profound decrease in sCD163 in our patients after therapy (P = 0.0037). Similar to sCD163, pre-treatment expression of CD163 on monocytes was significantly more enhanced in patients than that in controls (P = 0.0078). There was a trend towards down-regulation of the expression after therapy, nonetheless, the change was not statistically significant compared to the values before therapy (P = 0.8666). This was also confirmed by comparison with controls which displayed lower expression of CD163 than patients after therapy (P = 0.0019). The disease activity, expressed as PASI score, was significantly decreased in our patients by GT (P = 0.0001).ConclusionsWhile sCD163 level in psoriatic patients was diminished after GT therapy, CD163 expression on monocytes was altered only to a minor extent.     

Clinical significance of serum interleukin-6 and −174 G/C promoter polymorphism in Rheumatoid arthritis patients

Aim of the workTo evaluate the clinical significance of serum levels of interleukin-6 (IL-6) and ?174 G/C promoter polymorphism in Rheumatoid arthritis (RA) patients.Patients and methodsWe studied 37 RA patients and 10 age and gender matched healthy controls. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) were assessed. Serum IL-6 level was measured and promoter (?174G/C) genotyped.ResultsSerum IL-6 levels were significantly higher in RA patients compared to control (p = 0.04), especially those with CC promoter polymorphism. Twenty-four patients had GG IL-6 (?174 G/C) gene promoter polymorphism, 11 were GC and 2 CC. Nine controls were GG and 1 GC. In patients with more advanced polymorphism (?174 CC) there was a significantly increased functional impairment (HAQ score) (p = 0.029) and platelet count (p = 0.049). In those with GG genotype, there was a significant correlation between IL-6 and Morning stiffness duration (r = 0.44,p = 0.03), while those with GC genotype had a significant negative correlation of the IL-6 level with the parameters of disease activity and the DAS28 (r = ?0.69,p = 0.019). None of the studied parameters would predict the IL-6 promoter polymorphism.ConclusionSerum IL-6 levels and ?174 G/C promoter polymorphism were higher in RA patients than in healthy controls. The inverse relation of IL-6 with the DAS28 in those with an increased IL-6 promoter polymorphism may confirm its increased involvement in the pathogenesis of RA and in the increased disease activity which may point to the need for considering of anti-IL-6 agents in their management plan.     

The impact of fibromyalgia on disease assessment in rheumatoid arthritis patients

Aim of workTo explore the influence of the presence of concomitant fibromyalgia (FM) on the evaluation of disease activity score assessing 28 joints (DAS28), clinical disease activity index (CDAI) and modified health assessment questionnaire (MHAQ) in Egyptian patients with rheumatoid arthritis (RA).Patients and methodsThis study included 50 female RA patients; out of which 25 had concomitant FM (RAF group), the other 25 RA patients who served as controls did not have concomitant FM (RA group). All patients were subjected to an assessment of disease activity using the DAS 28 and the CDAI and assessment of functional outcome using MHAQ score.ResultsThe mean DAS 28 was significantly higher in RAF than RA patients (5.6 ± 1.1 versus 4.5 ± 1.3, P = 0.009). Also, the mean CDAI score was significantly higher in the RAF group (mean 23.3 ± 12.1 versus 13.7 ± 11.0, P = 0.002). The difference was attributed to significantly higher subjective items such as Tender joint count (TJC) and patient’s global assessment of general health (VAS-GH) in the RAF group. Mean MHAQ score was also higher in the RAF group (0.7 ± 0.6 versus 0.31 ± 0.4, P = 0.006).ConclusionFM is related to worse scores on the DAS28, CDAI and MHAQ in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 and CDAI scores because it is related to higher scores independently of objective evidence of RA activity.     

CD14++CD16+ monocyte subset expansion in rheumatoid arthritis patients: Relation to disease activity and interleukin-17

Aim of the workMonocytes are divided into three major subsets based on the expression of the cluster of differentiation CD14 and CD16. The aim of this work was to determine which of the CD16⁺ monocyte subpopulations is expanded in rheumatoid arthritis (RA) and its association with disease activity and interleukin-17 (IL17) levels.Patients and methodsFifty-three RA patients and 20 controls were enrolled in this study. Flow cytometry was performed to detect monocyte subsets and IL17 was measured by ELISA. Disease activity score (DAS28) was assessed.ResultsCD14⁺⁺CD16⁺ monocyte percentage was significantly higher in long standing RA patients compared with early patients and controls (p < 0.01, p < 0.001 respectively). It was significantly higher in patients with RA disease activity and remission compared with the controls (p < 0.001, p < 0.01 respectively). It was not significantly associated with resistance to disease modifying antirheumatic drugs (DMARDs), C-reactive protein, rheumatoid factor and anti-CCP positivity (p > 0.05). It significantly correlated with IL17 (p < 0.002). CD14⁺CD16⁺ monocyte percentage was not significantly correlated with any of the above parameters. IL17 level was significantly higher in patients with early and long standing RA compared to controls (p < 0.01, p < 0.001 respectively). IL17 was higher in RA patients with active disease compared to those in remission and controls (p < 0.01, p < 0.001 respectively). It was higher in RA patients resistant to DMARDs than in responding patients (p < 0.017).ConclusionCD14⁺⁺CD16⁺ monocyte subpopulation was expanded in long standing RA and was correlated with IL17 levels indicating its potential pathogenic importance in RA and may represent an attractive target for future therapeutic interventions.     

Serum calprotectin as a biomarker for Crohn's disease

Background and aimsIn Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease.MethodsThe STORI trial patients (n = 115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP).ResultsMedian serum calprotectin was 8892 ng/mL (range: 410–125,000 ng/mL) in Crohn disease patients as compared with 1318 ng/mL (range: 215.8–3770 ng/mL) in controls (P < 0.0001). Serum calprotectin was significantly higher for active disease (median = 19,584 ng/mL) than for inactive disease (median = 8353 ng/mL) (P < 0.0001). Serum calprotectin correlated with hsCRP (r = 0.4092, P < 0.0001) and CDAI (r = 0.4442, P < 0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r = 0.6458, 0.5515, 0.2577 with P < 0.0001, P < 0.0001, P = 0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675 ng/ml), appeared complementary to hsCRP (> 5 mg/l) and fecal calprotectin (> 250 μg/g) to predict relapse after infliximab withdrawal (P = 0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120).ConclusionsAs a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal.     

Proteinase-activated receptor 2 expression on peripheral blood monocytes and T-cells in patients with rheumatoid arthritis

Aim of the workProteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. The aim of this work was to evaluate the expression of PAR2 on peripheral blood monocytes and T-cells in rheumatoid arthritis (RA) patients and its correlation with disease activity.Patients and methodsForty RA patients and 16 healthy controls were enrolled in this study. Flow cytometry was performed to detect PAR2 expression. Disease activity score (DAS28) was assessed.ResultsPAR2 expression was significantly higher on monocytes in RA patients with active disease compared with patients in remission and healthy controls (75.4 ± 7.68; 56 ± 13.93 and 46.5 ± 9.8 respectively; p < 0.001). It was higher in RA patients in remission compared to healthy control (p = 0.01). No significant difference was found between patients with moderate and high disease activity. It significantly correlated with the erythrocyte sedimentation rate (ESR) and DAS28 (p < 0.001). It was significantly higher in patients with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positivity (p = 0.01, p < 0.001, respectively). It was not significantly associated with C-reactive protein (CRP) positivity and was not significantly different between early and long standing RA patients. PAR2 expression on CD3⁺ T-cells was not significantly different between patients with RA disease activity, patients in remission and healthy controls. Also it was not significantly associated with the ESR, DAS28, anti-CCP, RF and CRP positivity.ConclusionPAR2 expression on monocytes is consistent with a pathogenic role for PAR2 in RA and suggests that PAR2 may have utility as a marker for RA disease activity.     

Osteoprotegerin (OPG) and Matrix Gla protein (MGP) in rheumatoid arthritis patients: Relation to disease activity

BackgroundImbalanced Matrix Gla protein (MGP) and Osteoprotegerin (OPG) levels occur in inflammatory diseases.Aim of the workThe aim of the present study was to evaluate serum MGP and OPG levels in Rheumatoid Arthritis (RA) patients and study their relation to the disease activity.Patients and methodsForty-five female RA patients and 45 age and sex-matched healthy controls were included in this study. Disease activity score 28-C-reactive protein (DAS28-CRP) was used for the assessment of disease activity. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), MGP and OPG were measured in patients and controls. The associations of MGP and OPG with DAS28-CRP and the other laboratory and clinical variables were analyzed.ResultsRA patients had significantly higher serum OPG levels (408.3 ± 520.9 pg/ml) and hs-CRP (2.8 ± 1.9 mg/l) than the control (92.5 ± 86.3 pg/ml and 0.9 ± 1.5 mg/l respectively) (p < 0.001 each). There was no significant difference in MGP levels between the patients and control (p = 0.3). The correlation of OPG and MGP with DAS28-CRP in the patients was insignificant (p = 0.4 and p = 0.8 respectively). Age positively correlated with OPG (r = 0.32, p = 0.02), but not with MGP concentration (r = 0.05, p = 0.64) in the RA patients.ConclusionsThe significant elevation of the OPG level in RA patients may through light on its possible role in the pathogenesis of this disease and could be considered as a future therapeutic target. The significant correlation with age suggests that OPG may be an important mediator especially in elderly RA cases.