High prevalence of protein tyrosine phosphatase non-receptor N22 gene functional variant R620W in systemic lupus erythematosus patients from Kuwait: implications for disease susceptibility.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease which involves the loss of self-tolerance with hyperactivation of autoreactive T- and B-cells. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) encodes for lymphoid specific phosphatase (LYP) which is a key negative regulator of T lymphocyte activation. The aim of this study was to investigate the association between PTPN22 gene functional variant R620W and systemic lupus erythematosus (SLE) by comparing its prevalence in Kuwaiti SLE patients and controls. METHODS: The study included 134 SLE patients and 214 controls from Kuwait. The genotypes of PTPN22 gene functional variant R620W were determined by PCR-RFLP and confirmed by DNA sequence analysis in both SLE patients and the controls. RESULTS: A relatively high prevalence of the variant 620 W (T-allele) of the PTPN22 gene was detected in the SLE patients from Kuwait. 35.7% of the SLE patients had at least one variant allele (T-allele) compared to 15.9% in the controls. A statistically significant difference was detected in the frequency of variant genotypes, TT and CT between SLE patients and the controls (p < 0.0001). No association was detected between the PTPN22 gene variant and the Raynaud's phenomenon, renal involvement and severity of the SLE. CONCLUSIONS: The frequency of PTPN22 gene functional variant R620W reported in this study is amongst the highest compared to other world populations. A high prevalence of this variant in SLE patients in comparison to the healthy controls suggests its significant contribution in conferring susceptibility to SLE together with other factors.

Amelioration of human osteoarthritis symptoms with topical 'biotherapeutics': a phase I human trial.

Osteoarthritis (OA) treatments presently rely on analgesics, which manage pain but fail to restore imbalances between catabolic and anabolic processes that underlie OA pathogenesis. Recently, biologic (biotherapeutic) drugs, which alter the activity of catabolic agents such as nitric oxide and inflammatory cytokines in ways, allowing tissue regeneration, were evaluated for efficacy in OA treatment. These studies failed to demonstrate dramatic abatement of OA symptoms by these drugs, but suggested strategies by which biologic agents might be used to treat OA. The present review summarizes current understanding of OA pathogenesis and evolving treatments. Preliminary evaluations of a novel biotherapeutic strategy are presented here. Twenty OA patients receiving sour topical cherry seed extract (SCE), an inducer of heme oxygenase-1 (HO-1), a major physiological protectant against oxidative stress exhibited significantly decreased joint pain and activation of CD4+ T cells expressing inflammatory cytokines (p < 0.05), significantly decreased peripheral blood C-reactive protein (CRP), and increased leukocyte HO-1 (p < 0.05) in comparison with ten placebo-treated patients. SCE inhibits joint-damaging inflammatory mediator production. This agent therefore meets the main criterion for classification as a "biotherapeutic," or "biologic" agent. The negligible toxicity and low cost of such materials make them promising contributors to OA treatment, sustainable within resource limitations of a wide range of patients.

Association of angiotensin-converting enzyme (ACE) gene insertion-deletion polymorphism with spondylarthropathies.

Low back pain (LBP) is a common medical problem. Interaction between genetic and environmental factors predisposes individuals to LBP even at an early age. Inflammatory back pain or spondylarthropathies include ankylosing spondylitis (AS), psoriatic arthritis (PSA), reactive arthritis enteropathic and undifferentiated arthropathies. Angiotensin-converting enzyme (ACE) plays an important role in circulatory homeostasis, physiology of vasculature and inflammation. The insertion-deletion (I/D) polymorphism of the ACE gene has been shown to determine the plasma and tissue levels of ACE especially in the synovial fluid. The aim of this study was to investigate an association between ACE gene I/D polymorphism and inflammatory back pain (spondylarthropathies) secondary to ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease and undifferentiated spondylarthropathies. The prevalence of ACE gene I/D polymorphism genotypes was determined in 63 patients with inflammatory back pain by polymerase chain reaction (PCR) and compared with that in 111 healthy controls. Of the 63 patients studied, 45 (71.4%) were with AS, 13 (20.6%) were with PSA, 4 (6.3%) were with reactive arthropathy and 1 (1.6%) manifested undifferentiated arthropathy. There were 43 males and 20 females. Mean age of patients was 39.0+/-11.36 years, age at onset of spondylarthropathy was 27.7+/-7.49 years and disease duration was 10.3+/-7.74 months. The controls were selected to match with the patients group in terms of gender ratio, age and ethnicity. The ACE gene polymorphism showed an overall significant difference between patients and controls (p=0.050). When the ID and II genotype frequency was combined and compared with that for DD genotype amongst patient and control groups, a considerably higher incidence was detected for ID and II genotypes than the DD genotype in spondylarthropathy patients compared to that in the controls (p=0.036). This study showed a significant association of the I-allele of ACE gene I/D polymorphism with spondylarthropathy in Kuwaiti Arabs.

Angiotensin-converting enzyme gene polymorphism in patients with psoriatic arthritis.

To investigate the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in adults with psoriatic arthritis (PsA), a heterogeneous chronic disease with autoimmune pathology. ACE gene I/D polymorphism influences the plasma and tissue levels of ACE and has an involvement in inflammatory mechanism. The frequency of ACE gene I/D polymorphism genotypes was determined in 51 adults with PsA from Kuwait, and compared to that in 100 ethnically matched healthy controls using polymerase chain reaction. The distribution of ACE I/D polymorphism and allele frequencies in PsA patients were not significantly different from controls (P > 0.05). Further analyses of PsA patients showed that ACE I/D gene polymorphism was not associated with family history, clinical manifestations, and disease severity. However, the frequency of II genotype was significantly higher in patients with late disease onset than in those with early onset (25 vs. 3%; P = 0.04). No difference was found between the distribution of the ACE genotype in PsA patients and the general population in Kuwait. However, the presence of II genotype may confer susceptibility to the development of late onset PsA.

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.