Demographic, autoimmune, and clinical profiles of patients with systemic lupus erythematosus in Oman.

Seventy female and three male Omani systemic lupus erythematosus (SLE) patients are described. At disease onset, 45 (62%) were under 20 years of age, and the remainder were between 20 and 44. Of all cases, 48% were familial. Over 5 years, the cumulative frequencies of autoantibodies was: antinuclear antibodies (ANA) 97%, anti-double-stranded DNA (anti-dsDNA) antibodies 92%, extractable nuclear antigen (ENA) antibodies 64%, antineutrophil cytoplasmic antibodies (ANCA) 58%, antiphospholipid (APL) antibodies 80%, and rheumatoid factor (Rf) 22%. Ribonucleoprotein (RNP) antibodies were found in 15/45 younger-onset and 2/28 older-onset patients (chi(2)=6.63, P<0.02). The mean SLE disease activity score (SLEDAI) was 13.5+11.4, and the cumulative frequencies of systemic involvement were: neurological 33.8%, vascular 10.4%, musculoskeletal 53.9%, renal 50.7%, dermal 80.5%, serosal 23.9%, immunological 95%, constitutional 31.3%, and haematological 26.0%. Linear regression analysis showed that high-titre ANA were predictors for pyuria (odds ratio [OR] 9.06, P=0.01). Antiextractable nuclear antigen antibodies were predictors for disease of the neurological (OR 26.3, P=0.008) and serosal (OR 27.7, P=0.005) systems, and anti-Sm antibodies for alopecia (OR 5.93, P=0.088) and hypocomplementaemia (OR 14.6, P= 0.016). Antibodies of known diagnostic utility may also give insights into the pathogenesis of SLE.

Clinical features of Behçet's disease in patients in the Sultanate of Oman; the significance of antiphospholipid antibodies?

The prevalence of symptoms in 34 Omani patients with Behcet's disease (BD) was: recurrent oral ulceration 100%, arthritis/arthralgia and genital ulceration 74% each, folliculitis 64%, neurological lesions 62%, retinal vasculitis 30%, iritis and hypopyon 26%, gastrointestinal lesions 12%, venous thrombosis and cardiovascular lesions 9% each, and pleuropulmonary lesions and epididymitis 6% each. Antiphospholipid (APL) antibodies (both anticardiolipin [ACAs] and anti-beta2 glycoprotein I [abeta2GPIs]) were present in 11/34 (32%) of the BD patients and in 54/73 (74%) of Omani patients with systemic lupus erythematosus (SLE) (chi2 = 21.2, P<0.001). In patients possessing APL antibodies, there was no significant difference in mean antibody levels between BD and SLE patients. IgM isotype antibodies, in the absence of IgG, were more prevalent in BD (5/11) than in SLE (10/54) patients (chi2 =3.8, P = 0.05). The frequency of organ involvement was similar in patients with and without APL antibodies (chi2 = 1.226, P > 0.05). This study fails to demonstrate a pathognomonic role for APL antibodies in BD.

Tribal and geographical variations of lupus in the Sultanate of Oman: a hospital-based study.

Tribal differences are demonstrated in the presentation of lupus in Omani Gulf Arabs (OGA) and Omani Arabs of Persian descent (OAP), both groups resident in and indigenous to the Sultanate of Oman. The OAP have a lower risk of joint complications, skin rash, and dsDNA antibodies than OGA (beta coefficient and 95% confidence interval [CI], -35.6, -16.4, and -2.31 and -38.05 to -33.06, -19.49 to -13.3, and -4.1 to -0.6, respectively). The OGA have higher levels of IgG isotype APL antibodies than OAP, both anticardiolipin (ACA) (t= 1.75, P= 1.04) and anti-beta2glycoprotein I (infinitybeta2GPI) (t=3.64, P=0.004) antibodies, while OAP have higher levels of ACAs, IgM isotype (t=2.86, P=0.0024), than OGA. Antiphospholipid (APL) antibodies associate differently with clinical symptoms, both within OAP and between OAP and OGA. Patients from Dakiliyah have a higher risk of joint disease than those from Muscat (relative risk ratio 5.0, 95% CI 1.3-18.3). Differences in symptomatology suggest variations in genetic linkages to human systemic lupus erythematosus.

Serum levels of soluble Fas correlate with indices of organ damage in systemic lupus erythematosus.

OBJECTIVE: To evaluate whether the levels of soluble form of the Fas apoptosis antigen (sCD95/sFas) varied from those of healthy control subjects in a group of patients with systemic lupus erythematosus (SLE). This was done to determine whether sFas has a role in either the disease activity or the organ damage in SLE. METHODS: Serum levels of sFas were measured over a period of 4 y (277 determinations) in 39 Arab patients with SLE and 22 age-, gender-, and race-matched healthy controls using double antibody ELISA. SLEDAI scores for disease activity and SLICC/ACR scores for cumulative organ damage were determined. Serum levels of acute phase reactants, complement, inflammatory cell counts, levels of autoantibodies, and kidney and liver function test results were obtained retrospectively from clinical records. RESULTS: sFas levels were significantly higher in patients with SLE (n = 39, 277 determinations) (0.60 ng/ml +/- 0.38) than in healthy controls (n = 22) (0.26 ng/ml +/- 0.11) (P < 0.00001). The levels of sFas correlated with SLICC/ACR (r = 0.36; P < 0.02), but not with SLEDAI. sFas correlated with renal and liver function tests measured by s-creatinine (r = 0.38; P < 0.0001), creatinine clearance (r = -0.30, P < 0.001), s-albumin (r = -0.28, P < 0.0001), and ALT (r = 0.35; P < 0.00001), but did not correlate with the levels of acute phase reactants. CONCLUSION: sFas is elevated in sera of SLE patient. Since sFas correlates with indices of organ damage but not with disease activity, it may be a marker of organ damage in SLE and may act to protect certain organs from further damage by inhibiting Fas-mediated apoptosis.

Apoptosis and cell death in the endocrine system.

Inflammatory diseases of the endocrine system--such as thyroiditis, diabetes, and Graves' disease--are considered to be autoimmune in origin. More recently, these and other autoimmune diseases have been associated with defects in Fas apoptosis. The mutation of the Fas or Fas ligand (FasL) has been observed in a minority of patients with autoimmune disease. However, dysfunction of the Fas apoptosis signaling pathway or production of soluble factors, including sFas and sFasL, may be more prevalent. Certain endocrine tissues, such as the testes, are immune privilege sites. Defects in Fas and FasL expression in immune privilege sites can trigger an inflammatory response. Other factors that trigger inflammatory diseases of the thyroid or islets may be loss of self tolerance, leading to an autoimmune response. An infectious trigger or other environmental agent can initiate organ damage, leading to release of new antigens that initiate the autoreactive process. We have developed a murine cytomegalovirus model of Sjögren's syndrome in which defects in the Fas/FasL pathway are necessary to enable chronic inflammation, even after the initial virus has been cleared. Another interaction between the endocrine system and apoptosis is by direct hormone interaction. This is exemplified by the orphan steroid receptor Nur77. Nur77 is important for T cell apoptosis after signaling through CD3. We have demonstrated that a dominant-negative Nur77 transgenic mouse exhibits a defect in thymic selection of T cells. Therefore, there are many potential mechanisms by which endocrine glands or hormones can affect the Fas apoptosis pathway, resulting in either cell death or a chronic inflammatory disease in the endocrine system, leading to hypothyroidism and diabetes. This inflammatory dysfunction can be reversed by a dominant-negative I kappa B that prevents nuclear translocation of NF-kappa B. We have developed antigen-specific, antigen-presenting cells that express high levels of FasL that can prevent tissue-specific inflammatory disease. Treatment with these cells prevents development of diabetes in NOD mice. Further understanding of the role and regulation of apoptosis in diseases of the endocrine system (e.g., diabetes, thyroiditis) should lead to better methods of treatment and prevention of these diseases.