ASSOCIATION OF MHC CLASS I WITH SPONDYLOARTHROPATHIES IN KUWAIT

This study is the first to assess the prevalence of HLA B27 in Kuwaiti patients with ankylosing spondylitis (AS) or related spondyloarthropathies compared to healthy controls. Positive HLA B27 was found in nine (25.7%) of 35 patients, but only in 22 (4%) of 544 controls (P = 0.000). A significant difference in Cw2 and Cw6 between patients and controls was also found (P < 0.01 and 0.000, respectively), suggesting a linkage disequilibrium between B27 and Cw2 (P < 0.000) in the Kuwaiti population. These findings suggest that B27-positive Kuwaitis are at high risk of developing AS and spondyloarthropathies, especially if they carry Cw2 and Cw6. The importance of HLA Cw loci is becoming increasingly apparent in disease association studies.     

Clinical, biological and genetic study of 24 patients with ataxia telangiectasia from southern Tunisia

Ataxia telangiectasia is a multisystem disease with an autosomal recessive inheritance. It is characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, humoral and cellular immunodeficiencies and high incidence of neoplasia and radiosensitivity. A 5 year retrospective survey included 24 patients belonging to 17 families. Cerebellar ataxia was the first clinical symptom and was usually noticed when the child began to walk. Mean age of onset was 2.9+/-1.8 years. Oculocutaneous telangiectasia was present in 17 cases and appeared between 2 and 8 years and then spread in a characteristic symmetrical pattern. When ocular telangiectasia was absent (6 cases), the diagnostic of ataxia telangiectasia was retained on oculomotor apraxia (2 cases), recurrent sinopulmonary infections (3 cases) and/or a sib with typical ataxia telangiectasia (1 case). Recurrent sinopulmonary infections, absence or low serum level of IgA (78 p.100) and lymphopenia revealed immunodeficiency. Among 12 patients, chromosomal instability was observed in 5. Balanced rearrangements involving chromosomes 2, 7, 14, 22, 1, 3 and 11. The responsible gene, ATM, encodes a large protein kinase with a phosphatidylinositol 3-kinase-like domain. Ataxia telangiectasia patients have a 100 fold higher risk of cancer than the general population. We reported, in the same family two patients who developed neoplasia, (lymphoma and leukemia). During follow-up, a progressive worsening was observed in all cases. Three patients have died.     

Primary malignant melanoma of the esophagus

Primary malignant melanoma of the esophagus is a rare but aggressive tumor that accounts for less than 0.1-0.2% of all esophageal malignancies. The aim of this study was to report a case of primary malignant melanoma of the esophagus in a 72-year-old woman. The diagnosis was histologically proven, but the patient died despite extensive surgical resection.     

Lesch Nyhan syndrome: A novel complex mutation in a Tunisian child

Lesch Nyhan syndrome (LNS) is an X-linked recessive disorder due to complete deficiency of the hypoxanthine–guanine phosphoribosyltransferase (HPRT) enzyme. Defect of the enzymatic activity is related to mutations of the HPRT1 gene. The disorder severity is due to neurological features and renal complications. Up to now, more than 300 mutations have been reported. We report on a Tunisian child with a severe phenotype due to a novel identified complex mutation.     

Engineering of a recombinant trivalent single-chain variable fragment antibody directed against rabies virus glycoprotein G with improved neutralizing potency

Human and equine rabies immunoglobulins are currently available for passive immunization against rabies. However, these are hampered by the limited supply and some drawbacks. Advances in antibody engineering have led to overcome issues of clinical applications and to improve the protective efficacy. In the present study, we report the generation of a trivalent single-chain Fv (scFv50AD1-Fd), that recognizes the rabies virus glycoprotein, genetically fused to the trimerization domain of the bacteriophage T4 fibritin, termed ‘foldon’ (Fd). scFv50AD1-Fd was expressed as soluble recombinant protein in bacterial periplasmic space and purified through affinity chromatography. The molecular integrity and stability were analyzed by polyacrylamide gradient-gel electrophoresis, size-exclusion chromatography and incubation in human sera. The antigen-binding properties of the trimeric scFv were analyzed by direct and competitive-ELISA. Its apparent affinity constant was estimated at 1.4 ± 0.25 × 10⁹ M⁻¹ and was 75-fold higher than its monovalent scFv (1.9 ± 0.68 × 10⁷ M⁻¹). The scFv50AD1-Fd neutralized rabies virus in a standard in vitro and in vivo neutralization assay. We showed a high neutralization activity up to 75-fold compared with monovalent format and the WHO standard serum. The gain in avidity resulting from multivalency along with an improved biological activity makes the trivalent scFv50AD1-Fd construct an important reagent for rabies protection. The antibody engineering approach presented here may serve as a strategy for designing a new generation of anti-rabies for passive immunotherapy.     

Determinants of life satisfaction among stroke survivors 1 year post stroke

Stroke is the major leading cause of death and severe long-term disability worldwide. The consequences of stroke, aside from diminished survival, have a significant impact on an individual''s capability in maintaining self-autonomy and life satisfaction (LS). Thus, this study aimed to assess LS and other specific domains of LS in stroke survivors following their first-ever stroke, and to describe the relationship using socio-demographic and stroke-related variables.This study recruited 376 stroke survivors (244 men and 132 women, mean age: 57 years) 1 year following stroke. Data on participants’ LS (measured using the Life Satisfaction Questionnaire [LiSat-11]), socio-demographics, and stroke-related variables were collected.Univariate analysis showed that LS and the 10 specific domains were not associated with the patients’ gender or stroke type; however, age at onset, marital status, and vocational situation were significantly associated with some domains in LiSat-11 (Spearman''s rho = 0.42–0.87; all P < 0.05). Logistic regression revealed that verbal and cognitive dysfunction were the most negative predictors of LS (odds ratio 4.1 and 3.7, respectively).LS is negatively affected in stroke survivors 1 year post onset. The results indicate that recovering social engagement is a positive predictor of higher LS in stroke survivors. More importantly, the findings revealed that cognitive and verbal dysfunctions were the most prominent negative predictors of the overall gross level of LS. Multidisciplinary rehabilitation for stroke survivors is therefore critical.