Aqeel Ghanem

Bio: Aqeel Ghanem is an academic researcher from Mubarak Al Kabeer Hospital. The author has contributed to research in topics: Medicine & Rheumatoid arthritis. The author has an hindex of 5, co-authored 12 publications receiving 55 citations.

Th-17 related regulatory network in the pathogenesis of Arab patients with systemic lupus erythematosus and lupus nephritis

Abstract: Aim The present study aimed to identify the genes involved in the pathogenesis of systemic lupus erythematosus (SLE) in Arabs by investigating a panel of 84 genes related to the t helper (Th)17-related regulatory network and to further explore the expression levels of serum interleukin (IL)-17A and IL-17F in a studied cohort A comparative analysis of gene expression profile in SLE and lupus nephritis (LN) patients against that of healthy controls (HC) was performed Method A quantitative real-time polymerase chain reaction (PCR) (Th17 autoimmunity and inflammation) array analysis was performed in peripheral white blood cells of 66 SLE patients under specific medical treatment and 30 age/gender/ethnically matched healthy controls Statistical analysis was carried out using the RT2 Profiler TM PCR Data Analysis tool Results The analysis of Th17 pathway revealed 14 genes (IL-17A, IL-17C, IL-17D, IL-17F, IL-18, IL-12RB2, IL-23R, CCL2, CCL20, CXCL5, MMP3, RORC, STAT4 and TRAF6) that are differentially expressed in SLE and HC (fold change [FC] < 2, P < 00006) No significant difference in expression profiles was observed between SLE and LN A significant difference in serum concentration of IL-17A (P = 0002) and IL-17F (P = 0002) was observed between SLE (1391 ± 425) and LN (1826 ± 424) Conclusion Our study is the first to investigate a panel of 84 genes related to Th17 regulatory pathway in Arab SLE subjects and the first to explore the effect of current immunosuppression regimens on Th17 regulatory pathway It paves the way for understanding the etiology of SLE and autoimmune diseases in general

A Comparison of Rheumatoid Arthritis Patients in Kuwait with Other Populations: Results from the KRRD Registry

Abstract: Objective: Data on rheumatoid arthritis (RA) in Kuwait and The Middle East is scarce. Available data from Western countries may not be representative of the region. We describe RA patients in Kuwait and compare them with other RA populations and with Kuwaiti general population. Methods: Adult RA patients from Kuwait Registry for Rheumatic Diseases (KRRD), the first RA Original Research Article Al-Herz et al.; BJMMR, 14(9): 1-11, 2016; Article no.BJMMR.24673 2 registry in The Middle East, were studied from February 2013 through February 2015. Demographic, clinical and serologic data were compared with other RA populations and with Kuwaiti general population. Results: 835 patients were enrolled, 62.3% female. Mean age 50.6±12 years and disease duration 6.1±6 years. RA was diagnosed at a mean age of 44.9±12 years. 17.1% had family history of autoimmune rheumatic diseases. 3.1% had rheumatoid nodules. Rheumatoid factor (RF) and anticitrullinated peptide (ACPA) were detected in 75.6% and 57.8%, respectively. Both were positive in 49% (r=0.287, p=0.001). ANA was positive in 19.1%. Both ACPA and a combination of positive RF and ACPA were more in males (p=0.017, 0.004 respectively), whereas ANA was more in females (p=0.01). One third of male patients were smokers versus 1.9% of females. Smoking was correlated to RF (p=0.009) and ACPA (p=0,002). Difference in ACPA between genders was statistically explained by the predominance of smoking in males. Comorbidities included diabetes mellitus (DM) (20.8%), hypertension (20.2%), hyperlipidemia (10.5%) and coronary artery disease (CAD) (3.1%). 4 cases of cancer were reported. Conclusion: RA population in Kuwait includes less women than other RA populations but more than Kuwaiti general population. Family history is more common. A higher positive ACPA in males was explained by smoking difference. Hypertension and hyperlipidemia were less reported than in both Kuwaiti general population and other RA populations. CAD was similar to other RA populations. DM was more reported, reflecting its high background prevalence in Kuwait.

Influence of HumDN1 VNTR polymorphism on DNASE1 expression in systemic lupus erythematosus and rheumatoid arthritis.

Abstract: The purpose of this study was to analyze the effect of the HumDN1 VNTR polymorphism on DNASE1 mRNA expression and enzyme activity in lupus (SLE) and rheumatoid arthritis (RA) compared to healthy control (HC). Kuwait subjects (n = 500) matched by age/gender/ethnicity were genotyped by fragment-analysis. DNASE1 expression was analysed using quantitative Real-Time-PCR and sera from subjects were screened for DNase1 reduction activity by ELISA. Allele and genotype distribution of HumDN1 VNTR revealed a significant association with susceptibility to SLE and RA (p 1). Relative expression analysis revealed a significant increase in DNASE1 mRNA in SLE (p = 0.0001) and RA (p = 0.002) compared to HC. Stratification of subjects revealed, increased DNASE1 expression in SLE with 5/5 (p = 0.0001), 3/4 (p = 0.0001) and 3/5 genotype (p = 0.01). A reduction in DNASE1 expression was specifically observed in SLE with 4,4 genotype (p = 0.0004). RA patients with 3/4 genotype (p = 0.02) showed a significant increase in DNASE1 expression. Similarly a significant association was observed between DNase1 reduction activity and SLE (p = 0.0001). SLE patients with 3,4 (p = 0.0001) and 5,5 genotype (p = 0.0001) showed increased DNase1 reduction activity, while a lack of association was observed with RA. The present study is the first to reveal the effect of HumDN1 VNTR on DNASE1 expression in SLE and RA.

Kuwait association of rheumatology 2018 treatment recommendations for patients with rheumatoid arthritis

Abstract: The Kuwait Association of Rheumatology (KAR) aimed to develop a set of recommendations for the treatment of patients with rheumatoid arthritis (RA), tailored to the unique patient population and healthcare system of Kuwait Each recommendation was developed based on expert opinion and evaluation of clinical practice guidelines from other international and national rheumatology societies Online surveys were conducted to collate feedback on each KAR member’s level of agreement (LoA) with definitions of disease-/treatment-related terms used and the draft recommendations Definitions/recommendations achieving a pre-defined cut-off value of ≥ 70% agreement were accepted for inclusion Remaining statements were discussed and revised at a face-to-face meeting, with further modifications until consensus was reached A final online survey was used to collect feedback on each KAR member’s LoA with the final set of recommendation statements on a scale of 0 (complete disagreement) to 10 (complete agreement) Group consensus was achieved on 66 recommendation statements, including 3 overarching principles addressing the pharmacological treatment and management of RA Recommendations focused on treatment of early RA, established RA, patients with high-risk comorbidities, women during pregnancy and breastfeeding, and screening and treatment of opportunistic infections The KAR 2018 Treatment Recommendations for RA reported here are based on a synthesis of other national/international guidelines, supporting literature, and expert consensus considering the Kuwaiti healthcare system and RA patient population These recommendations aim to inform the clinical decisions of rheumatologists treating patients in Kuwait, and to promote best practices, enhance alignment and improve the treatment experience for patients

Enhancing the care of women with rheumatic diseases during pregnancy: challenges and unmet needs in the Middle East.

Abstract: Pregnancy in women with rheumatic disorders is known to be associated with risks for both the mother and fetus; however, these risks can be minimized with proper planning and careful management of the disease In the Middle East, there are specific cultural challenges that may have a negative impact on the care that women with rheumatic disorders receive There is a need for cross-collaboration between specialist physicians, improved awareness of rheumatic disorders among the general public and more open discussion with patients about the potential complications of pregnancy Women in the region are often unwilling to discuss their disease with their partner and are even less likely to seek advice regarding family planning from their physician The objective of this review is to highlight the specific challenges of pregnancy management and to discuss why establishing specialist pregnancy clinics for women with rheumatic disorders could be an effective solution Such clinics can provide high quality care before, during and after pregnancy as shown in several European and US centers Additionally, such clinics could be useful for the collection of pregnancy outcomes data from the Middle East, which may currently be lacking in the region, in order to highlight where further improvements can be made With specialist care and analysis of pregnancy outcomes, the standard of care for women with rheumatic disorders in this area could be significantly improved

Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases

Abstract: Osteopontin (OPN) regulates the immune response at multiple levels. Physiologically, it regulates the host response to infections by driving T helper (Th) polarization and acting on both innate and adaptive immunity; pathologically, it contributes to the development of immune-mediated and inflammatory diseases. In some cases, the mechanisms of these effects have been described, but many aspects of the OPN function remain elusive. This is in part ascribable to the fact that OPN is a complex molecule with several posttranslational modifications and it may act as either an immobilized protein of the extracellular matrix or a soluble cytokine or an intracytoplasmic molecule by binding to a wide variety of molecules including crystals of calcium phosphate, several cell surface receptors, and intracytoplasmic molecules. This review describes the OPN structure, isoforms, and functions and its role in regulating the crosstalk between innate and adaptive immunity in autoimmune diseases.

Safety and Efficacy of Baricitinib Through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis

Abstract: Objective. To assess the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) up to 128 weeks in a phase IIb study (NCT01185353). Methods. After a 24-week blinded period, eligible patients entered an initial 52-week open-label extension (OLE); patients receiving 8 mg once daily (QD) continued with that dose and all others received 4 mg QD. Doses could be escalated to 8 mg QD at 28 or 32 weeks at investigator discretion when ≥ 6 tender and ≥ 6 swollen joints were present. Patients completing the first OLE were eligible to enter a second 52-week OLE and receive 4 mg QD regardless of previous dose. Results. In the 4-mg (n = 108) and 8-mg (n = 93) groups, treatment-emergent adverse events (AE) occurred in 63% and 67%, serious AE in 16% and 13%, infections in 35% and 40%, and serious infections in 5% and 3% of patients, respectively. Exposure-adjusted incidence rates for AE for all baricitinib groups in the second OLE were similar to or lower than rates observed in the first OLE. No opportunistic infections, tuberculosis cases, or lymphomas were observed through 128 weeks; 1 death occurred during the first OLE. Among all patients in both OLE, the proportions who achieved disease improvement at Week 24 were similar or increased at weeks 76 and 128. Conclusion. In a phase IIb study in RA, the safety and tolerability profile of baricitinib, up to 128 weeks, remained consistent with earlier observations, without unexpected late signals. Clinical improvements seen in the 24-week blinded period were maintained during the OLE.

A Review of the Prevalence and Unmet Needs in the Management of Rheumatoid Arthritis in Africa and the Middle East.

Abstract: Estimates of the global prevalence of rheumatoid arthritis (RA) range from 0.24 to 1%, but vary considerably around the globe. A variation in RA prevalence is also expected across Africa and the Middle East, due to ethnic, climate, and socioeconomic differences. To assess the prevalence of RA in Africa and the Middle East, we searched Medline (via PubMed) and databases of major rheumatology conferences. Seventeen journal articles and 0 abstracts met the inclusion criteria. Estimated prevalence ranged from 0.06 to 3.4%. Most studies reported values near or below 0.25%. Consistent with data from other regions, RA was more prevalent among urban than rural populations, and among women than men. The women:men prevalence ratio ranged from 1.3:1 to 12.5:1, which suggests notable differences from the global average of 2:1. Relative increases in prevalence were observed in North Africa and the Middle East (13% since 1990) and Western Sub-Saharan Africa (14%), whereas rates in Eastern, Central, and Southern Sub-Saharan Africa show decreases (4–12%). Low disease awareness, delays to visit rheumatologists, and socioeconomic factors appear to hinder early diagnosis and aggressive treatment. Few countries have developed RA-specific treatment guidelines, and many physicians and patients face limited access to even basic treatments. An improved understanding of the epidemiology and management of RA, and the related socioeconomic consequences is necessary, so that targeted attempts can be made to encourage early diagnosis and treatment.