Faculty Bibliography

OBJECTIVE: To determine the urinary levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in patients with systemic lupus erythematosus (SLE) and to assess their relationship with clinical and laboratory features and the degree of activity and damage associated with the disease. METHODS: The study sample included 24 consecutive patients with SLE. 24-hour urine samples were collected for the determination of soluble VCAM-1 and ICAM-1 levels by ELISA. Disease activity was defined by the SLE Disease Active Index (SLEDAI) and disease outcome by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ ACR) damage index. RESULTS: The urinary soluble VCAM-1 level was significantly higher in patients with SLE compared to normal controls (32.35+/-34.27 vs. 4.66+/-3.8 ng/mg creatinine, p = 0.0005) and statistically significantly correlated with disease activity (SLEDAI), a low serum C3 level, decreased creatinine clearance and albuminuria, as well as with disease damage (SLICC/ACR damage index). In contrast, the urinary soluble ICAM-1 level was not significantly higher in the patients' group compared with the controls (4.5+/-5.19 vs. 2.72+/-2.31 ng/mg creatinine, p=0.2), but was statistically significantly correlated with hematuria and albuminuria. CONCLUSION: Our data suggest that the urinary level of soluble VCAM-1 significantly correlates with overall disease activity and damage scores, but not with nephritis in SLE.

Systemic lupus erythematosus-associated irreversible organ/system damage was previously associated with various clinical and demographic features. We analysed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) in a cohort of 151 Israeli patients followed for a mean (+/- s.d.) period of 45.7 +/- 37.4 months. Mean score of SLICC/ACR DI at the first and last encounters were 0.17 +/- 64 and 1.64 +/- 2.1, respectively (P < 0.0001). Multiple logistic regression analyses disclosed a statistically significant positive correlation with corticosteroid and cyclophosphamide therapy. Hydroxychloroquine therapy was significantly associated with lower SLICC/ACR DI. Although the size of our study group did not allow us to find specific organs/systems which were associated with the protective effect of hydroxychloroquine, we suggest this is due to the antiatherogenic effects attributed to antimalarial therapy in SLE.

Two patients with primary Sjogren's syndrome and T cell large granular lymphocyte (LGL) leukemia are described. One patient had evidence of T cell LGL salivary gland infiltration, suggesting a possible common etiopathogenesis for these 2 conditions.

In order to investigate the sub-typing of the B5 antigen in Israeli (Jewish and Arabic) patients with Behcet's disease (BD) allele-specific genotyping of B51 and B52 alleles was performed in Israeli BD patients and healthy controls. Among the HLA-B51-positive BD patients, B*5101 was found to be the predominant allele, identified in 62% of all BD patients and 78% of Jewish BD patients. HLA-B*5101 was also the predominant allele in HLA-B51-positive healthy controls. HLA-B*5108 and B*5104 alleles were identified in 23% and 15% of B51-positive BD patients, respectively. The HLA-B*5201 allele was identified in all HLA-B52-positive patients and controls. Our study suggests that both HLA-B*5101 and HLA-B*5201 are the dominant alleles of HLA-B5 in Israeli BD patients.

OBJECTIVES: The angiotensin-converting enzyme (ACE) gene polymorphism has been associated with worse outcome in various chronic glomerular disorders and in hypertension. Because nephritis and vascular morbidity are prominent determinants of outcome in systemic lupus erythematosus (SLE), we studied the distribution and prognostic effect the ACE genotype might have on the outcome of SLE. METHODS: Fifty-six consecutive Israeli SLE patients and 48 (sex and ethnic origin matched) healthy individuals were evaluated for the ACE genotype by a polymerase chain reaction-based assay. The clinical and laboratory parameters of the patients as well as the SLE disease activity index (SLEDAI) and the presence of hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, and stroke were correlated with the ACE genotype. RESULTS: The distribution of the ACE genotype D/D, D/I, and I/I in the lupus group was 59%, 36%, and 5%, respectively, similar to the distribution in the control group (54%, 31%, and 15%, respectively). We failed to find any significant association between the ACE genotype and disease manifestations, SLEDAI, renal function, or cardiovascular and cerebrovascular morbidity. The clinical and laboratory parameters associated with renal outcome and vascular morbidity in our cohort are described. CONCLUSIONS: No difference was found between the distribution of the ACE genotype in lupus patients and the general population in Israel. Renal function as well as cardiovascular and cerebrovascular morbidity among Israeli patients with SLE are disease-related and independent of the ACE gene polymorphism.

OBJECTIVE: The pathergy reaction is a unique feature of Behcet's disease (BD) and, according to the International Study Group (ISG), is among the major criteria required for the diagnosis. Different positive pathergy reaction rates in BD have been reported worldwide. We evaluated the prevalence of the pathergy reaction in Israeli BD patients, and its relation to mucocutaneous and systemic manifestations of the disease. METHODS: Forty-three patients were studied, all of whom fulfilled the ISG criteria for BD. The mucocutaneous and systemic disease manifestations were analyzed with respect to the presence of the pathergy reaction, and a systemic severity score for BD was calculated according to the potential morbidity and mortality associated with various clinical features. RESULTS: Nineteen patients (44.2%) had a positive pathergy test. The pathergy-positive and pathergy-negative BD groups showed a similar male:female ratio, age at disease onset, and mean disease duration. They also exhibited similar HLA-B5 levels and a similar frequency of oral ulcerations in close family members. The mucocutaneous manifestations, systemic disease expression, and severity score were similar in patients with and without the pathergy reaction. CONCLUSION: The presence of a positive pathergy reaction, although common in Israeli BD patients, is not associated with an increased risk for specific mucocutaneous or systemic manifestations of the disease, and probably does not predict a more severe disease course.

PROBLEM: To investigate if controlled ovarian hyperstimulation (COH) affects the expression of neutrophil adhesion molecules and if a correlation exists between neutrophil activation and serum sex-steroid levels. METHOD OF STUDY: The pilot study was carried out in the in vitro fertilization (IVF) unit of our department, and required no modification of our routine IVF protocol. Four patients arriving for baseline hormonal profile on day 1 of the menstrual cycle before initiation of COH (control group) and 11 patients admitted for oocyte recovery (study group) were included. Venous blood was obtained from all patients and examined for hormonal profile and neutrophil activation. The latter was performed by staining for the surface adhesion molecules beta2 integrin and L-selectin. Positive cell count and mean fluorescence intensity were determined by flow cytometry. RESULTS: While neutrophil L-selectin was significantly lower in the study group than in the control group, neutrophil beta2 integrin was nonsignificantly higher. Though no significant correlations were found between neutrophil adhesion molecules and patient age, serum estradiol level, and human chorionic gonadotropin level; neutrophil L-selectin was negatively correlated with serum progesterone levels. CONCLUSIONS: COH leads to neutrophil activation, which correlates with the degree of luteinization. Further studies are required to elucidate the relationship between the immune system and COH. These may lead to new strategies for promoting fertility and preventing complications of COH.

There were 55 Israeli patients with Behcet's disease (BD) included in a study conducted to determine the correlation between HLA-B5 and clinical manifestations and severity of the disease. The systemic manifestations of BD were analyzed in relation to HLA typing, and a systemic severity score for BD was calculated according to potential morbidity and mortality associated with various clinical features. Of the 55 patients, 42 (76.4%) were sephardic Jews, 2 (3.6%) were ashkenazi Jews, and 11 (20.0%) were Israeli Arabs. There were 39 (70.9%) HLA-B5 positive patients; they had a significantly higher incidence of thrombophlebitis and a lower rate of erythema nodosum. The HLA-B5-positive patients were significantly older at disease onset, and their severity score tended to be higher, although not statistically significant.The results of our study imply that HLA-B5 in Israeli patients is associated with specific clinical features, especially more vascular disease, and may be associated with a more severe course of BD. This is of general interest because American and North European patients also have less HLA-B5 and less severe disease. (J Clin Rheumatol 1999;5:137-140).

OBJECTIVE: To investigate headache in systemic lupus erythematosus (SLE) and its relation to other disease manifestations. METHODS: Clinical and laboratory variables of 148 SLE patients were prospectively recorded in a computed data base. RESULTS: The patients were divided into two groups. Group A consisted of patients who reported moderate to severe headache on at least two consecutive encounters, and Group B consisted of the remainder of the patients, with mild or no headache. The two groups did not significantly differ in age or in sex distribution. Patients in Group A suffered from more severe joint pain and inflammation, muscle pain, photosensitivity, mouth ulcers, fever and fatigue. They also had higher disease activity scores, and a higher number showed central nervous involvement. There were no significant differences between the two groups in any of the laboratory variables examined, nor in the proportion of patients with renal involvement. The prevalence of non-thromboembolic central nervous system (CNS) manifestations was 7.2%. The sensitivity of headache for the diagnosis of non-thromboembolic CNS manifestations was 90.9%, and the specificity was 29.2%. On logistic regression analysis, the total arthritis score, muscle pain, fatigue and photosensitivity were each found to be significantly independently related to headache. CONCLUSIONS: Headache is common in SLE, and in the majority of patients is related to musculoskeletal and constitutional disease manifestations.