Adel Al-Awadhi

Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population

Leptin, the obesity gene protein product, is a hormone with multiple physiological functions in the human. However, there are few reports in the literature on its role in trace element metabolism in the normal population. Therefore, we investigated the association among serum leptin, zinc, copper, and zinc/copper ratio in 570 healthy men and women aged 15 yr and older. Serum leptin assay was done with a commercial enzymelinked immunosorbent assay kit; serum zinc and copper levels were measured by an atomic absorption spectrophotometer. Serum leptin was found to be positively associated with age (r=0.254, p<0.001), sex (r=0.406, p<0.001), body mass index (BMI) (r=0.553, p<0.001), and serum copper (r=0.419, p<0.001), but negatively associated with the zinc/copper ratio (r=−0.423, p<0.001). There was no significant association between serum leptin and zinc (r=−0.131, p>0.05). When the confounding effects of age, sex, and BMI were removed, serum leptin was still positively associated with serum copper (r=0.197, p=0.02) and the serum zinc/copper ratio (r=−0.182, p=0.03). These results suggest that copper and not zinc has an effect on serum leptin levels.

Relations of Serum Interleukin 18 Levels to Serum Lipid and Glucose Concentrations in an Apparently Healthy Adult Population

Aim: To investigate the associations between serum interleukin (IL) 18 concentrations and indices of lipid and carbohydrate metabolism in healthy adults. Methods: Fasting serum concentrations of IL-18, glucose, total cholesterol, triglyceride, and high- and low-density lipoprotein cholesterols were measured in 570 apparently healthy adults. Results: Univariate linear and partial regression analyses showed that the serum IL-18 concentration was positively correlated with serum triglyceride and glucose concentrations in both obese and diabetic subjects after controlling for the confounding effects of age, sex, and body mass index. Conclusion: IL-18 may be associated with obesity and glucose intolerance.

Are 25(OH)D levels related to the severity of knee osteoarthritis and function

Objective: To investigate the effect of 25-hydroxyvitamin D [25(OH)D] in Kuwaiti patients with primary knee osteoarthritis (OA) and to assess its relation with radiological grading and functional status. Subjects and Methods: In this cross-sectional study, 25(OH)D was measured using radioimmunoassay in 99 patients [90 women and 9 men; mean age 56.5 ± 9.1 years (range: 36–80)] with clinical and radiological findings of primary knee OA. X-ray grading using the Kellgren-Lawrence grading scale and the Osteoarthritis Research Society International (OARSI) Atlas grading scale and functional assessments using Lequesne’s indices were evaluated in relation to the 25(OH)D level. Other variables studied were age at onset of symptoms, body mass index and duration of disease. Results: The age of the patients at the onset and the duration of disease were 51.58 ± 7.14 and 3.88 ± 2.51 years, respectively. Mean scoring for functional assessment was 10.31 ± 4.35 and mean Kellgren-Lawrence radiological grading was 2.43 ± 0.85. Radiological finding according to the OARSI Atlas revealed joint space narrowing of grades 2–3 in 87 (87.9%) patients and the presence of osteophytes in 55 (55.6%) patients. The mean value of 25(OH)D level was 11.4 ± 6.07 ng/ml. Of the 99 patients, 92 (92.9%) were vitamin D deficient. Comparison of 25(OH)D levels to radiological findings and different functional classes showed no significant association. Conclusion: Most of our patients had vitamin D deficiency, but the level of 25(OH)D was not related to the severity of the knee X-ray grading or to the functional assessment in our patients with primary knee OA.

Reference ranges of copper and zinc and the prevalence of their deficiencies in an Arab population aged 15-80 years.

Serum concentrations of copper and zinc were measured by flame atomic absorption spectrophotometry in 560 Kuwaitis aged from 15 to 80 yr who were in apparent good health to establish reference ranges and determine the prevalence of the deficiency of the trace metals. Zinc/copper ratios were derived by calculation. Because the mean±SD (µM) for copper in females (24.9±7) was significantly higher (p<0.0001) than in males (21.0±5.8) and vice versa for zinc (17.0±3.5 [males] vs 15.5±3.4 [females]) and zinc/copper ratios (0.87±0.28 [males] vs 0.67±0.27 [females]), gender-specific reference ranges were established in addition to reference ranges for the total population. The reference range for zinc was closer to those reported for other populations than was copper. Body mass index (BMI) and copper values were lower and the zinc/copper ratio was higher in the young (15–24 yr) compared to the older subjects. Copper concentrations were positively associated with BMI values (r=0.302, p<0.0001). Smokers had significantly lower (p=0.011) BMI than nonsmokers. The prevalence of copper and zinc deficiency, 0.36% and 0.53%, respectively, was low. Generally, the values for serum copper and zinc obtained for the Kuwaiti population studied suggest adequate dietary intake of the trace metals.

Frequency of abnormal thyroid function tests in Kuwaiti Arabs with autoimmune diseases.

Objectives: The purpose of this study was to examine the frequencies of abnormal thyroid function tests and serum thyroid autoantibodies in healthy Kuwaitis and those with autoimmune diseases. Subjects and Methods: Serum concentrations of sensitive thyrotropin, and free thyroxine were measured in 577 apparently healthy controls, 177 patients with rheumatoid arthritis (RA), 60 with systemic lupus erythematosus (SLE) and 25 with primary Sjogren’s syndrome (pSS) using the immunochemiluminescent assay method on IMMULITE 1000. Serum microsomal and thyroglobulin autoantibodies were also measured by passive hemagglutination assay. For analysis of the thyroid function tests, the subjects were classified into five categories: normal, subclinical hypothyroidism, overt hypothyroidism, euthyroid sick syndrome and biochemical hyperthyroidism. Results: Subclinical hypothyroidism was seen in 1.7% of healthy controls, 10.2% of RA, 13.3% of SLE, and 16% of pSS patients. Among RA patients, the frequency of subclinical hypothyroidism in females (11.4%) was significantly higher than among males (5.4%; p < 0.01). In SLE and pSS patients, all those with subclinical hypothyroidism were females. Overt hypothyroidism was seen in 1.4% of controls, 10.2% of RA, 8.3% of SLE, and 4% of pSS patients. Biochemical hyperthyroidism was seen in 0.2% of controls, 4.5% of RA, 5% of SLE and none of pSS patients. The euthyroid sick syndrome was seen in 0.4% of controls, 13.6% of RA, 16.7% of SLE and in none of pSS patients. Thyroid autoantibodies were present in 3.1% of controls, 12.4% of RA, 18.3% of SLE, and 12% of pSS patients. Conclusion: Our data show that abnormal thyroid function tests and thyroid autoantibodies occur frequently in Ku-waitis with autoimmune diseases. Therefore, ordering these tests in these diseases is recommended.

Incidence of musculoskeletal pain in adult Kuwaitis using the validated Arabic version of the WHO-ILAR COPCORD Core Questionnaire.

BACKGROUND The WHO-ILAR Community Oriented Program for Control of Rheumatic Diseases (COPCORD) primarily aims to estimate the burden of musculoskeletal symptoms/disorders. We estimated the incidence of musculoskeletal pain in the first community-based COPCORD study in Kuwait. SUBJECTS AND METHODS The validated Arabic version of the WHO-ILAR COPCORD Core Questionnaire was used in a survey of 2500 randomly selected Kuwaiti households to assess the frequency of musculoskeletal pain, disability, and health-seeking behavior in adult Kuwaitis. Those subjects reporting no musculoskeletal pain were identified and followed-up for a period of one year by contacting them every 2 weeks. Once a respondent reported pain, an appointment to report to hospital was offered and the subject was examined by a rheumatologist using American College of Rheumatology (ACR) criteria. RESULTS Of 5159 adults who were non-complainers in an earlier prevalence phase of the study, 3341 responded to phone calls (response rate of 65%). The incidence of musculoskeletal pain was 6.6% (95%CI, 3.4%-9.7%). Age- and sex-adjusted incidence rates were 7.2% (95%CI, 3.4%-10.5%) for females and 6.1% (95%CI, 3.1%-9.2%) for males. The incidence rate increased with increasing age, body mass index, and with being married. The common sites of pain were knee, low back and shoulder. CONCLUSION The incidence of musculoskeletal pain among Kuwaiti adults is reported for the first time. Further studies adopting the same instrument in other communities are warranted to compare with our findings.

Human leukocyte antigen DRB1*04 is associated with rheumatoid arthritis in Kuwaiti patients

OBJECTIVES Rheumatoid arthritis (RA) is a common, complex autoimmune disease known to be associated with inheritance of certain human leukocyte antigen (HLA)-DR alleles in different populations. This study investigated the association of DRB1 alleles in Kuwaiti patients with RA. MATERIALS AND METHODS DRB1 alleles were analyzed in 47 Kuwaiti patients and 70 ethnically matched controls using a DNA-based sequence specific primer (SSP) method. RESULTS The frequency of DRB1*04 allele was higher in patients compared to the controls (P < 0.012). The association with of HLA-DRB1*04 allele in our patients with RA was accounted for mainly by the seropositive group of patients (P < 0.05). Moreover, five patients were homozygous for DRB1*4 compared to none in the controls. None of the other DRB1 alleles tested was significantly higher in the patients. All patients homozygous for the DRB1*04 allele were females. There was no statistically significant difference in the frequency of DRB1*04 allele in patients classified according to presence of erosive disease or extra-articular manifestations. CONCLUSION Our results indicate that in Kuwaiti patients, RA is associated with the presence of DRB1*04 allele. The lack of association with severity or the phenotype of RA is not surprising since this is a hospital-based study where patients tend to have a more severe disease.

Sour cherry (Prunus cerasus) seed extract increases heme oxygenase-1 expression and decreases proinflammatory signaling in peripheral blood human leukocytes from rheumatoid arthritis patients

Sour cherry seed extract (SCE) was evaluated for its capacity to inhibit lipopolysaccharide-treated human peripheral blood T cells expressing tumor necrosis factor-alpha, and the chemokine interleukin-8. Both proteins are diagnostic biomarkers for inflammatory pathologies. Peripheral blood leukocytes from 11 rheumatoid arthritis (RA) patients and 8 healthy control subjects were co-cultured for 24h in lipopolysaccharide and the extract, then evaluated by flow cytometry for T cell activation and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1) expression. There was a dose-dependent decrease in expression of the immunophenotypes: CD3+TNF-α+, and CD3+IL8+ in cultures from RA patients to a greater extent than in cells from healthy participants. These results suggest that the extract may have a modulatory roll in RA and other inflammatory disorders via the induction of HO-1, thus abating oxidative stress and strengthening regulation of pro-inflammatory signaling pathways.

The effect of neutralizing antibodies on the sustainable efficacy of biologic therapies: what’s in it for African and Middle Eastern rheumatologists

Over the last decade, biologic therapeutic proteins have advanced the treatment of diseases such as rheumatoid arthritis (RA). Therapeutic antibodies such as infliximab, adalimumab, rituximab, tocilizumab, golimumab, certolizumab pegol, the receptor construct etanercept, and abatacept, an anticluster of differentiation (CD)80/anti-CD86 fusion protein, are used as treatment for RA and ankylosing spondylitis (AS). Infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept are inhibitors of tumor necrosis factor (TNF), a key regulator of inflammation. Left untreated, progression of rheumatic diseases due to inflammation can lead to irreversible joint damage and serious disability. One limitation for the use of therapeutic antibodies is immunogenicity, the induction of antibodies by the adaptive immune system in response to foreign substances. The development of antidrug antibodies (ADAs) has a varying impact on the clinical efficacy of biologic agents for the treatment of RA and AS, depending on whether the ADAs are neutralizing or non-neutralizing. Studies have indicated that neutralizing ADAs are associated with a reduced efficacy, decreased drug survival, increased instances of dose escalation, and adverse events. Comparison studies of anti-TNF biologics have demonstrated that each drug has a different sustained efficacy profile depending on immunogenicity. The purpose of this review is to provide rheumatologists with information regarding the effect of neutralizing antibodies on the sustainable efficacy of anti-TNF biologic therapies. This information will be of value to practicing rheumatologists in Africa and the Middle East who should take into account the potential for changes in the efficacy and safety of biologic therapies and closely monitor patients under their care.

Effects of rituximab treatment on the serum concentrations of vitamin D and interleukins 2, 6, 7, and 10 in patients with rheumatoid arthritis

Background Rituximab, a monoclonal antibody that selectively targets CD20-positive B-lymphocytes, is used for the treatment of patients with rheumatoid arthritis (RA) with an inadequate response or tolerance to tumor necrosis factor inhibitors. The objective of this study was to investigate the effects of rituximab treatment on the serum concentrations of vitamin D, interleukin (IL) 2, IL-6, IL-7, and IL-10 in patients with rheumatoid arthritis (RA). Methods Forty-five patients, aged 25–78 years, were enrolled into a cohort prospective study. All patients were treated with intravenous rituximab. Disease activity score-28 (DAS-28) and serum concentrations of rheumatoid factor (RF), C-reactive protein (CRP), anticyclic citrullinated peptide (anti-CCP), erythrocyte sedimentation rate (ESR), health assessment questionnaire (HAQ), vitamin D, ILs 2, 6, 7, and 10 were estimated in the patients before and after treatment with rituximab. Results DAS-28, HAQ score, and serum concentrations of CRP, RF, anti-CCP, IL-2, IL-6, IL-7, IL-10, and ESR significantly decreased after treatment. All 45 patients had vitamin D deficiency before treatment and this did not significantly change after treatment. However no significant association was found among serum vitamin D concentration and any of the ILs. Conclusion We concluded from this study that although rituximab treatment of patients with RA significantly reduced their disease activity and serum concentrations of IL-2, IL-6, IL-7, and IL-10, it did not significantly alter their vitamin D status. Furthermore, no significant association was found among serum vitamin D concentration and any of the ILs.