HLA-DRB1 genes and disease severity in rheumatoid arthritis in Turkey.

OBJECTIVE: Association with human leukocyte antigen (HLA)-DRB alleles, implicated in the aetiopathogenesis of rheumatoid arthritis (RA), is found to be different in various ethnic groups. This study aimed to investigate DRB1 alleles in RA patients in Turkey, and to examine the effect of these alleles on disease severity. METHODS: We performed PCR-based DRBI genotyping of 104 RA patients recruited from clinical settings and 110 healthy controls. HLA DRB1 alleles frequencies in RA patients and healthy controls were determined. Phenotype frequencies of patients and controls were compared. Disease severity was assessed by radiological erosion, presence of extra-articular involvement, and functional index. RESULTS: Significant differences were in the frequencies of DRB1*04 (46.2% versus 20.9%, p < 0.001), DRB1*0401 (10.6% versus 0%, p < 0.001), DRB1*0405 (8.7% versus 0%, p = 0.001), DRB1* 0404 (15.4% versus 3.6%, p < 0.01), DRB1*01 (21.2% versus 10.9%, p < 0.05) and DRB1*0101 (16.3% versus 5.5%, p = 0.01) between RA patients and controls. HLA-DRB1 alleles did not show any association with seropositivity, extra-articular involvement, radiological erosion, or functional index. CONCLUSION: Our results suggest that the HLA-DRB1 alleles, particularly HLA-DRB1*04 and subtypes, were associated with RA.

The prognostic value of peripheral blood lymphocyte subsets in patients with bladder carcinoma treated using neoadjuvant M-VEC chemotherapy.

OBJECTIVES: To assess the prognostic value of peripheral blood lymphocyte subsets in patients with bladder cancer who were treated with neoadjuvant chemotherapy. PATIENTS, SUBJECTS AND METHODS: Thirty patients with a histological diagnosis of invasive bladder transitional cell carcinoma and 30 age-matched controls with no evidence of cancer and immunological disorders were evaluated. Peripheral blood samples were assessed in both groups using monoclonal antibodies. Patients with bladder cancer who achieved complete or partial responses and those who had progression of the disease after systemic chemotherapy with methotrexate, vinblastine, epirubicin and cisplatin were compared according to the pretreatment values of the peripheral blood lymphocyte subsets. RESULTS: There were no significant differences in B lymphocyte levels between the groups. In patients with bladder cancer, the percentages of T lymphocytes (P<0.01), natural killer (NK) cells (P<0.05) and the CD4+/CD8+ ratio (P<0.05) were significantly lower than in the control group. In patients who responded to the chemotherapy regimen, the pretreatment values of T lymphocytes (P<0.001), the CD4+/CD8+ ratio (P<0.01) and NK cell levels (P<0.01) were significantly higher than in the patients who did not. CONCLUSION: In patients with invasive bladder carcinoma, cell-mediated immunity may have a role in the resistance to this malignancy and in these patients the pretreatment levels of T lymphocyte subsets may be an indicator of the potential response to chemotherapy.

Systemic amyloidosis and sacroiliitis in a patient with systemic lupus erythematosus.

We report a case of a 25-year-old female with juvenile onset systemic lupus erythematosus who developed systemic secondary amyloidosis with renal and gastrointestinal involvement. She has also had radiological signs of bilateral asymptomatic sacroiliitis without lower back pain or HLA-B27 antigen.

Analysis of the peripheral blood lymphocyte subsets in patients with bladder carcinoma.

OBJECTIVES: To evaluate the immune system of patients with bladder transitional cell carcinoma (TCC) by using peripheral blood lymphocyte subsets and to further compare the relationship between these subsets with respect to tumor stage and grade (superficial versus invasive and low versus high grade). METHODS: Thirty patients with superficial TCC of the bladder, 30 patients with invasive TCC of the bladder, and 30 age- and sex-matched control subjects without any malignancy or immunologic abnormality were included in this study. The peripheral blood lymphocyte subset analysis was performed in all patients before any treatment was performed. RESULTS: All lymphocyte subset values of patients with invasive bladder cancer, except B cell value, were significantly lower (P < 0.01) than the values of the control group. There were no significant differences between the lymphocyte subset values of patients with superficial bladder cancer and those of control subjects. The comparison of the lymphocyte subset values of the patients with superficial versus invasive bladder carcinoma revealed that in patients with invasive bladder carcinoma, the numbers of T and natural killer (NK) cells were significantly lower (P < 0.05) than those of patients with superficial bladder carcinoma. Patients with high-grade tumors had significantly fewer (P < 0.05) T and NK cells than patients with low-grade tumors. CONCLUSIONS: Our results indicate that analysis of mean NK and T cell values and the mean ratio of CD4+/CD8+ cells in peripheral blood might be a useful adjunct for the clinical evaluation of patients with bladder cancer.

Adhesion molecule expression in erythema nodosum-like lesions in Behçet's disease. A histopathological and immunohistochemical study.

Behçet's (BD) is a systemic inflammatory disease with histological evidence for vasculitis. Leucocyte-leucocyte and leucocyte-endothelial cell interactions are critical in inflammatory reactions that are influenced by the expression, activation and shedding of adhesion molecules. We investigated the expression of some adhesion molecules (E- and L-selectin, VLA-4, ICAM-1, PECAM-1, VCAM-1 and CD18 and CD11c chains of beta-2 integrins) on endothelial and inflammatory cells by immunohistochemistry on cryostat sections of erythema nodosum lesions taken from 15 patients with BD and 12 patients with erythema nodosum of unknown cause. Hematoxylin-eosin stained sections of all specimens were also assessed. The major histopathological findings were perivascular mononuclear cell infiltration and secondary vasculitic changes with no difference between the two groups (P > 0.05). However, the frequency of thrombophlebitis was higher in BD (P < 0.001). Endothelial and inflammatory cell adhesion molecule expression did not show any significant difference between groups (P > 0.05). Although VCAM-1 expression and intensity on endothelial cells of BD patients seemed to be lower, this did not reach statistical significance (P = 0.056). We concluded that subcutaneous thrombophlebitis is an important feature of erythema nodosum like lesions in BD, which is almost impossible to understand by physical examination alone. Colchicine, which is known to have some influence on adhesion molecules, might have affected our results, as these showed no significant difference regarding adhesion molecules between the two groups.

The frequency of autoantibodies in Turkish patients with lupus nephritis.

We analysed the frequency of autoantibodies in 44 patients with lupus nephritis. Antinuclear antibody (ANA) was found in 91% of patients by an indirect immunofluorescence technique on HEp-2 cells at the time of study. Anti-dsDNA antibodies were found at high levels in most of the patients using the SynELISA test, which reveals both high and low avidity antibodies, but only in 64% of patients using the DAKO assay, which reveals high avidity antibodies. Anti-histone antibodies were found in 52% of the patients. Anti-SSA/Ro antibodies were positive in 27% of all patients; these patients also had prominent cutaneous involvement and photosensitivity. The frequency of anti-SSB/La and Anti-Sm antibodies was 7%. Immunoblotting experiments confirmed the findings shown by the techniques described above, and anti-ribosomal antibodies were found to be positive in more cases by the latter assay. IgA rheumatoid factor (RF) was more frequent (20.4%) than IgM RF (9.9%). In conclusion, Turkish patients suffering from lupus nephritis seem to express a total autoantibody profile similar to that reported for systemic lupus erythematosus from other parts of Europe.

Lupus vulgaris in a patient with systemic lupus erythematosus and persistent IgG deficiency.

We present the case of a patient with juvenile onset systemic lupus erythematosus (SLE) who developed a persistent, acquired hypogammaglobulinaemia with IgG deficiency. The hypogammaglobulinaemia was probably a complication of high dose corticosteroid treatment. The serum IgG level remained subnormal despite intravenous immunoglobulin therapy. Lupus vulgaris, which developed on the nasal cartilage in this patient with SLE, is not an expected finding. This patient is probably the first reported case of SLE associated with lupus vulgaris.

Seizures and hepatotoxicity following sulphasalazine administration.

Sulphasalazine (SSZ) is a widely used second-line agent for several rheumatic diseases. Most of its side effects are relatively minor and dose dependent. We report a patient with juvenile onset chronic arthritis who developed hepatotoxicity and seizures on the third week of SSZ when the daily dose was increased to 2 g. Clinical and laboratory findings of liver and central nervous system toxicity gradually returned to normal in the month following SSZ withdrawal.

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with allergic rhinoconjunctivitis.

Intercellular adhesion molecule-1 (ICAM-1), a member of immunoglobulin supergene family with a five-domain structure, is known to play an important role in inflammatory disease. We measured levels of soluble ICAM-1 in sera of 25 patients with allergic rhinoconjunctivitis (7 male, 18 female: age range 14-47 years, mean 29.8 +/- 9.2) and 20 healthy subjects (11 male, 9 female: age range 22-48 years, mean: 33.3 +/- 7.6). All allergic patients had positive history, positive skin prick test and conjunctival provocation test, and radioallergosorbent test for specific allergens. Soluble ICAM-1 in serum samples was determinated by ELISA. The mean serum sICAM-1 levels, in healthy subjects was 193.3 +/- 68.8 ng/ml and in patients with allergic rhinoconjunctivitis was 212.6 +/- 50.9 ng/ml. There were no difference in sICAM-1 levels in both of the groups (P > 0.05). In male patients with allergic rhinoconjunctivitis, sICAM-1 levels (mean: 234.5 +/- 55.0 ng/ml) were higher compared to female patients with allergic rhinoconjunctivitis (mean: 204.1 +/- 48.1 ng/ml) and control group (P < 0.05 and P < 0.05 respectively). Soluble ICAM-1 levels were high in patients with allergic rhinoconjunctivitis who had high level of symptom score.

The early effect of specific immunotherapy on lymphocyte response to PHA and allergens in atopic patients with allergic rhinitis.

In the first part of this study, peripheral lymphocyte subpopulations and their proliferative response to PHA and allergens were investigated in the 30 patients with allergic rhinitis compared to 20 healthy non-atopic individuals. Data obtained employing a PHA-induced lymphoproliferative response assay revealed that the allergic rhinitis generated significantly less activity than did the normal control group. Significantly decreased ration of CD4+/CD8+ T cells was noted in the patients with allergic rhinitis. Mean values of stimulation indices by allergen extracts were higher in the patients sensitive to same antigen than others especially in concentration of 1000 SQU/ml. Stimulation of active lymphocytes revealed no statistically significant group differences between allergens. In the second part of the study, the early effect of immunotherapy on T cell subsets and lymphocyte proliferative response to PHA and allergens were examined in the peripheral blood lymphocytes of patients. A significant increase in PHA-induced and in allergen induced lymphoproliferative response were observed in all patients after sixth months of immunotherapy. It is concluded that there may be an association between allergic rhinitis and deficiency of circulating CD4+ cells but further studies are required to substantiate this hypothesis.

Fibronectin and circulating immune complexes in Behet's disease.

Being a high-molecular-weight adhesive glycoprotein, fibronectin (Fn) is suggested to be a component of immune complexes and may participate in the clearance of immune complexes. In Behçet's disease (BD), a multisystem disorder of unknown etiology, immune complexes have been shown to be deposited in affected tissue during disease activity, suggesting an immune mechanism. This study investigates the relationship between Fn and circulating immune complexes (CIC) and evaluates the changes in the levels of Fn and CIC along with disease activity. In 63 patients (31 active, 32 inactive) with BD, plasma Fn and serum CIC, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and the third and fourth components of the complement system (C3, C4) were studied. The mean ESR, CRP, C3 and C4 levels of active BD patients were found to be significantly higher than those of the inactive BD patient group. Although the mean Fn and CIC levels of BD patients were not significantly different from those of the healthy control group, Fn and CIC values of active BD patients were significantly lower than in the inactive group. Moreover, no significant correlation was observed among Fn levels and ESR, CRP, C3, C4 and CIC levels in BD patients. The result of this study suggest that the variation in Fn concentration is independent of the acute-phase response. The lack of relationship between the CIC and Fn concentrations indicates that IC deposition in the vessel wall is independent of the CIC levels. In order to determine the exact roles of Fn and IC, further studies in tissue specimens are required.

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with systemic lupus erythematosus.

Circulating sICAM-1 is known to be elevated in various inflammatory disorders. It is further suggested that elevated levels correlate well with disease activity in several autoimmune disorders. The objectives of this study are to determine the serum sICAM-1 levels in patients with systemic lupus erythematosus (SLE) and correlate sICAM-1 levels with clinical and laboratory (ESR, CRP, anti-dsDNA) measures of disease activity. Forty-one patients (34 female, 7 male) all fulfilling 1982 ARA classification criteria for SLE and 16 healthy controls (8 female, 8 male) were included in the study. Disease activity was measured according to SLEDAI. sICAM-1 was determined by ELISA. Mean sICAM-1 in SLE patients (339 +/- 161 ng/ml) were significantly higher than in the controls (216 +/- 85 ng/ml) (p < 0.005). Although slightly elevated in active patients, there was no statistically significant difference between mean sICAM-1 levels of active and inactive SLE patients (349 +/- 183 ng/ml and 316 +/- 103 ng/ml respectively) (p > 0.05). We could not find a correlation between sICAM-1 levels and any organ involvements. Similarly, no significant correlation was found between ESR, CRP, anti-ds-DNA and sICAM-1. These results suggest that although higher than normal, sICAM-1 levels in SLE do not provide additional information over conventional activity markers.

Evaluation of interleukin-6 in rheumatoid arthritis as an activity criterion.

This study evaluated interleukin-6 levels as an activity criterion in rheumatoid arthritis (RA) and compared if with other activity criteria. We evaluated 35 patients with active RA, 31 with inactive RA, and 25 patients with osteoarthritis, in addition to 28 healthy individuals. Serum interleukin-6 levels were higher in active RA patients than in those with inactive RA, or osteoarthritis and healthy individuals (P < 0.001). Serum interleukin-6 levels of patients with active RA were positively correlated with the erythrocyte sedimentation rate, C-reactive protein, and alpha 2-globulin levels (P < 0.001), but there was a negative correlation with serum albumin levels (P < 0.05). We conclude that interleukin-6 can be responsible for both the most systemic manifestations of RA and for its local manifestations.

Elevated levels of soluble intercellular adhesion molecule-1 correlate with disease activity in Behçet's disease.

The objective of this study was to measure soluble intercellular adhesion molecule-1 (sICAM-1) in patients with Behçet's disease (BD) and to analyse the relationship of sICAM-1 levels with clinical and some laboratory measures of disease activity. Forty patients with BD fulfilling the International Study Group Criteria for the diagnosis of BD and 20 healthy controls were studied. Twenty patients had active, and 20 patients had inactive disease. Serum sICAM-1 was determined by a sandwich ELISA. The mean (+/- SD) sICAM-1 level was significantly higher in the whole BD group (297.3 +/- 86.6 ng/ml) than in the healthy controls (213 +/- 83.5 ng/ml; P < 0.05). The mean sICAM-1 levels in active and inactive BD patients were 315.7 +/- 76.3 ng/ml and 258.3 +/- 73.3 ng/ml, respectively. The mean sICAM-1 level in active patients was significantly higher than in inactive patients and healthy controls (P < 0.02 and P < 0.001, respectively). No statistically significant difference in mean sICAM-1 levels was found between inactive BD patients and healthy controls (P > 0.05). There was no statistically significant difference between the mean sICAM-1 levels of active patients with (351.3 +/- 77.2 ng/ml) or without vascular lesions (292 +/- 68.8; P > 0.05). In spite of a positive correlation between disease activity and both erythrocyte sedimentation rate and C-reactive protein (CRP; P < 0.01), we found no correlation between sICAM-1 and either of them (P > 0.05). The elevated levels of sICAM-1 may be due to endothelial cell activation and/or damage or may be the result of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioimmunoblastic lymphadenopathy with disproteinemia arising in a patient with rheumatoid arthritis.

Angioimmunoblastic lymphadenopathy with disproteinemia (AILD) is a systemic lymphoproliferative disorder characterized by constitutional symptoms such as generalized lymphadenopathy, hepatosplenomegaly and skin rash. In this article, we report on a patient with seronegative Rheumatoid Arthritis of 18 years duration who recently developed AILD.

Plasma von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and antithrombin III levels in Behçet's disease.

Sixty-three patients with Behçet's disease (BD), 30 patients with recurrent oral ulcer and 30 healthy individuals as control group were included in the study. ISG criteria was used for the diagnosis of BD and patients were classified as active and inactive and evaluated accordingly. In the patient and control groups, von Willebrand factor (vWF), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) levels were determined using ELISA method and antithrombin III (AT-III) by nephelometric methods. High levels of endothelial product, vWF in the active Behçet patient group (p < 0.005) supports endothelial destruction due to vasculitis related with BD. In the active patient group tPA levels were significantly lower (p < 0.05) than the inactive and control groups with higher levels of PAI (p < 0.05 and p < 0.01) respectively. In Behçet disease, besides the decrease in tPA synthesis, high PAI levels also can affect tPA decrease and lead to inhibition of fibrinolytic activity. In active Behçet group, levels of AT-III were low and no significant difference was observed in recurrent oral ulcer and control groups. This situation may arise from the excessive use of AT-III in active disease. In conclusion, high levels of vWF in Behçet patients is thought to arise from vasculitis and high levels of PAI from the accumulation of thrombocytes on the damaged surface of endothelium leading to a decrease in tPA levels and inhibition of fibrinolytic activity.

Characteristics of headache in migraine without aura and episodic tension-type headache in the Turkish population according to the IHS classification.

We evaluated the characteristics of headache in migraine without aura and episodic tension-type headache diagnosed according to the International Headache Society (IHS) Classification. Fifty migraine without aura and 50 tension-type headache patients were selected prospectively. Fifty-eight percent of migraineurs had pain of a pulsating quality; 88% had severe pain and 74% had unilateral pain; aggravation by routine physical activity was reported by 96%. Episodic tension-type headache was of a pressing quality in 52%, moderate in 40%, bilateral in 82% and aggravated by routine physical activity in 16%. Nausea and/or vomiting, photophobia and phonophobia were reported significantly more commonly in migraineurs than tension-type headache patients.