Biomedical subjects

C A Kanawati

Publications and source records attributed to C A Kanawati.

7 recordsLinked to original sources

PubMed2004

Analysis of the CC chemokine receptor 5 (CCR5) Delta32 polymorphism in Behçet's disease.

Chemokines are important determinants of the early inflammatory response. The CC chemokine receptor 5 (CCR5) Delta32 variant results in a non-functional form of the chemokine receptor, and has been implicated in a variety of immune-mediated diseases. To investigate its role in the pathogenesis of Behçet's disease, we studied 350 patients and 519 healthy controls from three ethnic groups. While significant inter-ethnic variation in allele frequency was observed, no association was identified with disease, even when data were stratified by the known susceptibility gene HLA-B*51.

Alleles↗

PubMed2000

Intercellular adhesion molecule-1 gene polymorphisms in Behçet's disease.

Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been implicated in the susceptibility to inflammatory diseases, including multiple sclerosis and inflammatory bowel disease. The expression of both soluble and tissue ICAM-1 is increased in Behçet's disease (BD) but the contribution of ICAM-1 gene polymorphisms to this disease remains unknown. Associations with BD have been reported for genes within the MHC, including HLA-B51, TNF and MICA, but the role of non-MHC genes in BD remains largely unexplored. We have investigated the frequency of the R/G 241 and K/E 469 ICAM-1 gene polymorphisms in 83 patients with BD disease and 103 healthy controls, all of Palestinian and Jordanian descent, and demonstrated an association between BD and the ICAM-1 E469 allele (Pc = 0.046, OR = 2.1). Among patients, no association was found between the presence of ocular disease and ICAM-1 polymorphisms. While the functional correlate of this polymorphism remains unclear, this finding indicates that a genetic polymorphism in the ICAM-1 gene domain, which is independent of the MHC, may contribute to disease.

Behcet Syndrome↗

PubMed1999

MIC-A allele profiles and HLA class I associations in Behçet's disease.

Recently a new family of non-classical MHC molecules, the MHC class I chain-related protein (MIC), encoded by genes located in the major histocompatability complex have been identified. On the basis of the location of MIC genes and the structure and expression of MIC molecules it has been postulated that MIC may be a susceptibility factor in Behçet's disease (BD). We investigated the association of the 16 described external domain alleles and the transmembrane triplet repeats of MIC-A with BD in a Middle Eastern population. DNA from ninety-five patients and 102 age- and sex-matched controls were analyzed by polymerase chain reaction using allele specific primers. Our results show an increase of MIC-A*009 in the BD patient group 44/95 (46%) compared with controls 24/102 (24%) (chi2=11.3, OR=2.8, P=0.00078). MIC-A*009 was also found to be strongly associated with HLA-B51 in the patients 39/44 (88%) when compared with controls 10/24 (42%) (chi2=4, P=0.04). MIC-A*009 was also found in linkage disequilibrium with HLA-B52, but only in controls. The A6 form of a MIC-A transmembrane triplet repeat was found to be significantly raised in the patients (80/95; 84%;) compared with controls (58/102, 57%) (chi2=17.5, OR=4, P=0.000028). Although the MIC-A associations described are highly significant, the association with HLA-B51 independently remains the most significant factor (chi2=56.8, P<10(-6)). The data suggests that as both MIC-A*009 and A6 are in strong linkage disequilibrium with HLA-B51, they are unlikely to be the susceptibility gene for BD but may be markers for additional risk factors.

Adolescent↗

PubMed1999

Factor V Leiden mutation is associated with ocular involvement in Behçet disease.

PURPOSE: Behçet disease is a systemic disease of young adults characterized by venous occlusion in both the deep venous and retinal circulations. In severe ocular disease, blindness may occur despite immunosuppressive treatment. The most common inherited risk factor for the development of idiopathic venous thrombosis is the presence of the Factor V (FV Leiden) mutation, which confers resistance to activated protein C. The association of FV Leiden with Behçet disease has been reported, but its influence on ocular disease is not known. We therefore investigated the prevalence of this mutation in patients with Behçet disease to determine its contribution to the presence and severity of ocular disease. METHODS: One hundred and six Middle Eastern patients satisfying international criteria, and 120 healthy control subjects without a history of venous thrombosis were included in the study, and patients underwent standard examination by two ophthalmologists with an interest in Behçet disease. Genomic DNA was extracted from peripheral blood leukocytes and screened for the FV Leiden mutation with the polymerase chain reaction method with sequence-specific primers (PCR-SSP). RESULTS: FV Leiden was detected in 19% (23/120) of the control population compared with 27% (29/106) of all patients with Behçet disease (P = .13). However, among patients with Behçet disease who had ocular disease (75/106), the prevalence of FV Leiden was significantly higher (32%) than it was in control subjects (P = .04). Furthermore, ocular patients with Behçet disease in whom retinal occlusive disease was observed (25/75) had the highest expression of FV Leiden (44%). CONCLUSIONS: These data suggest that FV Leiden may be an additional risk factor for the development of ocular disease and, in particular, retinal vaso-occlusion, and it may contribute to the poor visual outcome in these patients.

Adolescent↗

PubMed1999

HLA and tumour necrosis factor (TNF) polymorphisms in ocular Behçet's disease.

The role of HLA-B*51 and other major histocompatibility complex (MHC) genes in Behçet's disease (BD) remains unknown. We have performed HLA and tumour necrosis factor (TNF) polymorphism analysis in BD and evaluated their contribution to ocular disease. In this study, 102 patients and 115 controls of Middle Eastern descent were investigated by HLA and B*51 subtyping using novel primers, and by LT alpha NCo 1 and TNF 308 promoter polymorphism analysis. The frequency of the HLA-B*51 family of alleles was raised in patients compared to controls (66% vs. 15%, Pc=2.5x10(-12), OR=10.9). The odds ratio (OR) of this group of alleles for subgroups of patients was as follows: non-ocular patients 7.8, all ocular patients 12.6, blind patients >22. HLA-B*51 subtyping detected B*5101, 07, 08 and 09 alleles, with a similar frequency among patients and controls. HLA-Cw*1602 was associated with B*5108, but was not an independent risk factor for disease. The LT alpha (TNFB*2) allele was associated with HLA-B*51 among patients and the frequency of this allele was significantly higher among completely blind patients compared to both non-ocular patients (P=0.048, OR >3.6) and to healthy controls (P=0.022, OR >4.3). The rare TNF-2 polymorphism at the TNF -308 promoter position was associated with HLA-B*50 (not B*51), and was not associated with BD. Thus, in this population the HLA*B51 family of alleles is a strong risk factor for BD, and in particular the development of ocular disease. HLA-B*51 subtyping did not define new markers for BD. A primary role for TNF gne polymorphisms in BD was not identified, but co-expression of the TNFB*2 allele with HLA-B*51 may contribute to severity of ocular disease.

Adolescent↗

PubMed1998

Soluble adhesion molecules in Behçet's disease.

BACKGROUND: Behçet's disease (BD) may lead to blindness in up to 25% of eyes. Soluble (s)ICAM-1 but not sVCAM-1 is associated with relapse in idiopathic uveoretinitis and is reported to be raised in BD patients. We have investigated the levels of sICAM-1 and sVCAM-1 in Palestinian patients with BD and related them to both ocular and systemic disease activity and to immunosuppressive treatment. METHODS: A total of 51 patients (43 male, 8 female; mean ages 29.8 & 31.9 yr) were examined at the St John Ophthalmic Hospital during a one year period (135 consultations). Disease activity was determined from history and standard ocular examination. Anterior uveitis, vitritis and retinal vasculitis acted as markers of ocular inflammation. Peripheral venous sICAM-1 and sVCAM-1 levels were determined by standard ELISA. A total of 53 healthy age- and sex-matched clinic staff members acted as controls. RESULTS: sICAM-1 and sVCAM-1 were both significantly lower in patients on systemic immunosuppression than in those off treatment (p < 0.001). Among patients off systemic treatment, sICAM was higher in the group with active systemic disease but quiet eyes (p = 0.003), but not in those with active ocular disease (p = 0.09), compared to controls. sVCAM was not raised in either group. CONCLUSION: Systemic immunosuppression was associated with reduced sICAM-1 and sVCAM-1, supporting a role for adhesion molecules in the pathogenesis of BD. sICAM-1 levels were raised in association with inflammatory features implicating endothelial activation in active BD. The mean sICAM-1 was higher in active ocular patients than controls.

Adolescent↗

PubMed1995

Intraocular lens implantation in children in the West Bank and Gaza.

In order to evaluate the efficacy and safety of intraocular lens (IOL) implantation in paediatric aphakia, we reviewed the records of a consecutive series of 40 children, under 15 years of age, who had IOLs inserted for congenital and developmental cataracts between September 1990 and December 1992. Visual results and lens-induced complications were evaluated in 67 eyes with a mean follow-up of 27 months (range 12-38 months). In 52 eyes the cataract was removed by limbal lens aspiration and in 15 eyes by pars plicata lens aspiration. One-piece PMMA Sinskey-type posterior chamber implants were used in all cases. Sixty-three eyes had primary and 4 eyes secondary implants. Seventeen (49%) of 35 eyes with congenial cataract and 25 (78%) of 32 eyes with developmental cataract achieved a visual acuity of 6/18 or better. Marked anterior uveitis with pupillary membrane formation occurred in 9 (13%) of the 67 eyes. Visually significant posterior capsule opacification occurred in 5 (28%) of the 18 eyes with intact capsule. Our results demonstrate the suitability of IOL implantation in children from an area of low socioeconomic background, and suggest that IOL implantation is an effective and safe procedure for correction of paediatric aphakia. This may have implications for similar populations.

Adolescent↗