Abraham Weinberger

Identification of alpha-tropomyosin as a target self-antigen in Behçet's syndrome

Behçets syndrome is a multi‐system inflammatory disease affecting mainly the oral and urogenital mucosa and the uveal tract. The etiology and pathogenesis of Behçets syndrome areunknown, but autoimmune mechanisms are implicated. We initiated this work to identify self‐antigens targeted by patients with Behçets syndrome. We used patient sera to immuno‐blot tissue lysates, and we found that some patients manifest antibodies to a 37‐kDa band. The 37‐kDa band was detected in extracts of skin, tongue, vagina, muscle and heart but not in brain, kidney, lung, liver, intestine and thymus. In‐gel digestion and mass spectrometry revealed the band to be α‐tropomyosin. Autoimmunity to α‐tropomyosin can be pathogenic; immunized Lewis rats developed lesions inthe uveal tract and skin, with features of Behçets disease.

Seasons of the Year and Activity of SLE and Behçet's Disease

Patients with systemic lupus erythematosus (SLE) were evaluated using a telephone questionnaire on the activity of various disease manifestations during the seasons of the past year. The results were compared to those of patients with Behcets disease (BD), using the same questionnaires, and analyzed in relation to the mean temperature, humidity, barometric pressure, and ultraviolet radiation (UVR) in the patients location, obtained from the official Israeli Meteorological Service. It was found that SLE patients had a tendency towards winter worsening of clinical manifestations, shown as increased incidence of joint pains, weakness, fatigue, Raynauds phenomenon, and rash, as well as increased number of hospital admissions, sick leaves, and need to raise the dose of medications. The symptoms of patients with BD were not correlated to seasons of the year, except for increased joint pains in autumn and spring. We suggest that UVR accumulation might cause exacerbations in SLE patients several months after prolonged exposure to sunlight in the summer.

Evaluation of disease activity in rheumatic patients by leucocyte adhesiveness/aggregation.

Previous work has shown that leucocyte adhesiveness/aggregation (LAA), as measured by the leukergy test, correlates well with disease severity in rheumatic patients. As LAA is probably a manifestation of the acute phase reaction various components of the acute phase reaction were measured in order to identify the best marker of disease activity. In addition to LAA, the following variables were measured in 79 patients with various rheumatic diseases and in 10 controls: white blood cell and platelet counts, erythrocyte sedimentation rate, haptoglobin, fibrinogen, C reactive protein, albumin, globulin, caeruloplasmin, alpha 1, alpha 2, beta, and gamma globulin, and haemoglobin concentrations. Patients were graded according to the state of their disease as mild, moderate, or severe. The extent of leucocyte adhesiveness/aggregation in peripheral blood proved to be the best laboratory variable for the grading of disease activity. Correct grading was obtained in 63% of the patients by means of the LAA, compared with 48% with C reactive protein, 41% with caeruloplasmin, 40% with haptoglobin, and 32% with haemoglobin. It is suggested that LAA of the peripheral blood during inflammation may be used as a reliable marker of disease severity.

Immunomodulatory Effect of Sertraline in a Rat Model of Rheumatoid Arthritis

Objective: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) modulate immune system functionality. SSRIs are the preferred treatment for major depressive disorder (MDD). A high rate of MDD is observed in rheumatoid arthritis (RA) patients. The aim of this study was to evaluate immunological effects of SSRIs in a rat model of RA. Methods: Adjuvant arthritis was induced in 8-week-old Lewis rats; in the first set of experiments following the induction, 15.3 or 30.6 mg/kg of sertraline was daily injected into the ankle joint of the left rear leg. Clinical disease activity was evaluated and the findings compared with the 3 untreated legs and with control groups given methotrexate (MTX) or vehicle only at the same site. In a second set of experiments, the effect of 5, 25 and 50 mg/kg daily oral sertraline was evaluated in the same rat model. Splenocyte viability and inflammatory mediators were evaluated. Results: The sertraline-treated rats showed a significant reduction in clinical arthritis compared to controls, at all doses given, accompanied by a significant increase in interleukin 10 and a decrease in tumor necrosis factor-α levels and cycloxygenase-2 production, without lymphotoxicity. There was no significant difference from MTX, the first-line treatment for RA patients. Oral sertraline had a significant anti-inflammatory effect at all doses. There was no treatment × time effect. Conclusion: The beneficial effects of sertraline in this rat model of arthritis have clinical implications for its use in humans. Large-scale clinical efficacy trials are needed.

Serum cobalamin and transcobalamin levels in systemic lupus erythematosus

PURPOSEnThe purpose of this study was to assay serum cobalamin levels in patients with systemic lupus erythematosus (SLE) as there are few case reports on the association of pernicious anemia and SLE.nnnPATIENTS AND METHODSnSerum cobalamin levels were assayed in 43 female SLE patients by a radio-dilution assay using purified intrinsic factor.nnnRESULTSnCobalamin levels were found to be significantly lower in the SLE group compared with a normal control group, eight of whom (18.6%) had serum cobalamin levels equal to or lower than 180 pg/mL (mean: 129.25 +/- 40.05 pg/mL). None of the SLE patients had been found to have pernicious anemia. The transcobalamin II level and unsaturated vitamin B12 binding capacity, but not the cobalamin level, were positively correlated with SLE activity.nnnCONCLUSIONnOur results may indicate a subtle cobalamin deficiency in SLE patients without pernicious anemia.

Prevalence of Behcet's disease among adult patients consulting three major clinics in a Druze town in Israel.

To evaluate the prevalence of Behçet’s disease (BD) in a Druze community in Israel, we conducted a two-stage clinic-based survey in an Israeli Druze town. The first stage aimed to identify patients with recurrent aphthous stomatitis (RAS) in all patients who visited three of the largest clinics in the town during a period of 6xa0months. The second stage aimed to identify those patients with RAS who fulfilled the diagnostic criteria for BD according to the International Study Group (ISG) criteria. One thousand and eighty-three out of about 4,000 registered subjects were interviewed, 63 of whom had RAS (5.8%). Two patients fulfilled the ISG criteria for BD, resulting in a calculated prevalence in the range of 2:1,083–2:4,000, i.e., 50–185:100,000. Another two patients with oral and genital aphthosis but without eye or skin lesions were diagnosed as suspected BD. The very high prevalence of BD, as found in our study, places the Druze among the populations with the highest prevalence of the disease all over the world, though selection biases could account for overestimation as well as underestimation of the actual BD prevalence. Our findings call for genetic studies to explore whether there is a genetic predisposition to BD in this population.

Association of HLA-B5 with Clinical Expression and Severity of Behcet's Disease in Israel.

There were 55 Israeli patients with Behcets 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).

Behcet disease in adult Druzes in north Israel: the influence of ethnic origin on disease expression and severity.

Background:Behcets disease (BD) is known to vary in severity and manifestations in different populations. Objective:In an attempt to sort out genetic and environmental influences on disease expression, we carried out a study to assess the clinical features of BD in the adult Druze and Arab populations in north Israel, comparing 2 disparate ethnic groups of similar genetic background inhabiting the same geographic region. Methods:We compared 23 Druze and 30 Arab patients with BD. All patients fulfilled the classification criteria of the International Study Group for BD. Results:Manifestations were similar in 2 groups. The most frequent BD manifestations among the Druzes were recurrent oral aphthae (100%) and genital aphthae (61%) versus 100% and 53% in Arab patients, followed by inflammatory ocular involvement, 65% versus 53%, respectively. Arthritis was noted in 39% of Druze, with 27% in Arabs. Anterior uveitis occurred in 9 Druze patients (48%) and panuveitis in 4, with no case of blindness when compared with 30% with anterior uveitis, 4 with panuveitis, and 4 cases of blindness (P < 0.04) among the Arabs. One Druze BD patient had deep vein thrombosis versus 8 Arab patients (P < 0.017). No pulmonary embolism, aortic aneurysm, nor valvular involvement was documented in the Druze versus 1 case of each in Arabs. No case of neuro-Behcet was reported in Druzes versus 6 cases of neuro-Behcet among Arabs (P < 0.023). The severity score was 4.0 (SD, 1.2) in Druze and 5.8 (SD, 1.9) in Arabs (P = 0.0004). The prevalence of HLA B51 did not differ significantly between the groups. Conclusion:Druze BD patients in Israel have a milder disease than do Arabs, similar to observations in familial Mediterranean fever. Druze BD patients had significantly less severe ocular disease and neurologic manifestations. Our results suggest an ethnic influence on expression of BD not related to HLA B 51.

Inflammatory arthritis of the hands as expressed by the impressionists in the Orsay Museum.

An extensive study looking for signs of inflammatory arthritis in the paintings of the impressionists was performed at the Orsay Museum in Paris, France. Of the 435 paintings reviewed, 3 works by different painters were found to show signs of inflammatory arthritis of the hands. We suspect that the importance of the arthritis in the models’ lives led the painters to emphasize this condition in their paintings.

Animal Models of Behçet’s Disease

Animal models for Behcet’s disease (BD) can be divided according to the proposed etiological paradigms. These include environmental pollution and infectious (bacterial and viral) models, as well as various autoimmune and transgenic animal models. The environmental pollution model, though resembles the multisystem symptoms of BD, has limitations to become utilized as a model for the disease since it is difficult to produce and the onset of symptoms appears erratically in a wide time range. The Streptococcal models have similarity only to the eye involvement in BD. This model is simple to induce with high rate of homogeneity. The HSV model has multisystem manifestations resembling BD; it has a moderate reproducibility. The autoimmune model utilizing S-Ag is a monosymptomatic model of BD-like uveitis. This model is easy to induce, and extensive studies elucidated some of the immunological characteristics of BD including the paradigm of anti-HLA autoimmunity. The α-tropomyosin model shares some clinical features of BD. This model has a potential to become a useful autoimmune model for BD. The only published trial to establish a transgenic model for BD did not show any significant similarity to the human disease except hyper-responsiveness of neutrophils.