Patient characteristics in Behçet's Syndrome and their associations with major organ involvement: a single-centre experience of 2118 cases.

Objectives: To evaluate the demographic and clinical characteristics of patients with Behçet's syndrome (BS), and to define their associations with the presence of major organ involvement (MOI).Method: Medical records of 2118 patients (964 males, 1154 females) were analysed retrospectively. MOI was defined as the presence of at least one of vascular, eye, nervous, or gastrointestinal system involvement. Univariable and multivariable binary and ordinal logistic regression analyses were applied to assess the factors that were potentially associated with MOI.Results: The mean ± sd age at diagnosis was 30.5 ± 9.4 years. Genital ulcer and joint involvement were more common in females (both p < 0.001), while MOI was more frequent in males (p < 0.001). Genital ulcer (p < 0.001) and vascular involvement (p = 0.006) were more common in patients with a younger age at diagnosis, while joint involvement was more common in older patients. A total of 1097 patients (51.8%) had at least one MOI, 322 (15.2%) at least two MOIs, and 48 (2.3%) at least three MOIs. Male gender, smoking history, and absence of genital ulcer were significantly associated with MOI in multivariable binary logistic regression. Multivariable ordinal regression analyses confirmed the association between MOI and male gender and smoking, but not the protective effect of genital ulcers. In both regression analyses, we found no significant effects of age, human leucocyte antigen-B51, skin involvement, or joint involvement on MOI.Conclusion: Male gender and positive smoking history have a significant influence on the presence of MOI in patients with BS.

The Relationship between Serum IL-17 and IL-23 Levels, and Other Disease Activity Parameters in Patients with Behçet's Disease

ABSTRACT Objective: To investigate the relationship between disease activity and the involvement of Behçet's disease (BD) and serum levels of interleukin (IL)-17 and IL-23. Methods: Sixty patients with BD and 20 healthy control group subjects were included in this study. The patients were divided into four groups according to clinical findings as follows: entero-Behçet, mucocutaneous-Behçet, neuro-Behçet and vascular-Behçet. The serum levels of the IL-17 and IL-23 levels were evaluated using enzyme-linked immunosorbent assay. Results: Of the BD patients, 15 (25%) had active disease and 45 (75%) had inactive disease. The serum levels of IL-23 and IL-17 were statistically significantly higher in the patients with BD than in the control groups (p < 0.05). A significant relationship was also observed between the disease activity, and both the erythrocyte sedimentation rate and the C-reactive protein levels (p < 0.05). The mean serum levels of IL-17 and IL-23 in patients with active disease were 0.07 ± 0.25 pg/ml and 36.0 ± 30.5 pg/ml, respectively. There was no statistically significant relationship between the disease activity and the serum levels of IL-17 and IL-23 (p > 0.05). There were also statistically significant relationships between the disease activity and uveitis, retinal vasculitis or superficial thrombophlebitis. Conclusion: No relationship was found between BD and serum levels of the IL-17 and the IL-23.

Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

The role of HLA-DRB1 shared epitope alleles in predicting short-term response to leflunomide in rheumatoid arthritis.

OBJECTIVES: To investigate the role of shared epitope (SE) alleles in the short-term clinical response to leflunomide for the treatment of active RA. METHODS: In an open-label, multi-centre study of 16-weeks duration, 93 patients (82% female) fulfilling ARA 1987 RA criteria were treated with leflunomide (100 mg loading dose for 3 days, then 20 mg/day as the maintenance dose). The primary efficacy criterion was the response status according to the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score-28 (DAS28) activity measure. SE determinations have been undertaken by polymerase chain reaction and sequence-specific oligonucleotide genotyping methods. RESULTS: The mean (s.d.) Disease Activity Score-28 (DAS28) was 5.1 (1.3) before the treatment, which was significantly decreased after 16 weeks [3.0 (1.1), P < 0.001]. According to the EULAR response criteria, 55 patients (59.1%) were classified as good responders. SE was positive in 51 (54.8%) of the patients, with 13 (13.9%) having SE homozygosity or carrying any two SE alleles. Among SE-positive patients, 68.6% (35/51) were good responders, compared with 47.6% (20/42) in SE negatives (P = 0.04). No difference was present according to SE hetero- or homozygosity (68.4 vs 69.2%). RF was also present significantly more frequently in the SE-positive group compared with negatives (78.4 vs 57.1%, P = 0.03). However, no significant difference was observed in the prevalence of RF positivity in patients with a good clinical response (72.7 vs 63.2%, P = 0.32). CONCLUSIONS: The results suggest that HLA-DRB1 SE presence may favourably affect the outcome of leflunomide monotherapy in an unselected group of RA patients with an active disease and naive to leflunomide.

Specific immunotherapy-induced Sjögren's syndrome.

BACKGROUND: Allergen-specific immunotherapy (SIT) is a well-documented treatment for allergic rhinitis, asthma, and allergy to bee venoms. Side-effects of SIT in long-term have not been well documented yet. Herein, we report a case of Sjögren's syndrome following SIT. CASE: The patient, a 25-year-old Caucasian woman, was started on subcutaneous grass-pollen immunotherapy. The patient's autoantibodies before the SIT screening tests were negative. We determined that anti-extractable nuclear antigen (ENA) was positive (ENA = 98.4, normal range 0-25 U) on routine screening tests at 44 weeks of her treatment, and then SIT was discontinued. The patient complained of burning and itching in her eyes for 6 months. Schirmer's and salivary flow tests were positive. Although antinuclear antigen and rheumatoid factor were negative, anti-SS-A/Ro was positive. Viral hepatitis markers were negative. Minor salivary-gland biopsy was performed, which showed grade 4 sialoadenitis. The HLA type of the patient was B55 (B22), Bw6, Cw1 for class I and DR11, DR52, DQ7 (DQ3) for class II. After the immunotherapy had been stopped, there were no changes in the symptoms and laboratory findings of the patient during the 1st year of follow-up. CONCLUSION: This is the first case to be reported of Sjögren's syndrome following SIT. Patients undergoing SIT must be carefully followed up for the development of autoimmunity and an autoimmune disease.

Serum-soluble selectin levels in patients with rheumatoid arthritis and systemic sclerosis.

Soluble forms of selectins may play a regulatory role in inflammatory responses that are key to the pathophysiology of rheumatic diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). The aim of this study was to examine whether the elevated serum-soluble (s) selectin levels are associated with RA or SSc. Serum sE-, sL- and sP-selectin levels were measured by sandwich enzyme-linked immunosorbent assay in 34 RA patients, 30 SSc patients and 16 healthy subjects. The levels of sE-selectin were significantly higher in RA and SSc patients than those in healthy subjects. The sL-selectin level was significantly lower in RA patients compared to healthy subjects. Serum sP-selectin levels were not significantly different among the study groups. The active RA patients had significantly higher serum sE- and sL-selectin levels compared to inactive RA patients. Also, some correlations were observed between the serum selectin levels and measures of disease activity such as erythrocyte sedimentation rate and C-reactive protein in RA patients. The higher levels of sE-selectin were found in SSc patients with pulmonary fibrosis, and there was also a negative correlation between diffusion capacity for carbon monoxide and serum sE-selectin. Serum levels of selectins may provide a useful additional marker for disease activity in RA patients and for disease severity in SSc patients.

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.

Serum IFN-gamma and IL-10 levels before and after specific immunotherapy in patients with allergic rhinitis.

Although a detailed explanation of the mechanism of immunotherapy is not known, several immunologic explanation have been proposed. It's said that T cell-cytokine profile changed with allergen immunotherapy. In our study we evaluated IFN-* and IL-10 levels before and after immunotherapy in patients with allergic rhinitis. Twenty patients (mean age; 27.3 +/- 4.84), 8 male, 12 female with allergic rhinitis, mean duration of disease was 5.55 +/- 1.23 years and 13 healthy controls, 5 male, 8 female (mean age: 28.38 +/- 5.61) were enrolled in the study. Immunotherapy was performed for grass pollen allergen extract to patients with allergic rhinitis for 31.5 +/- 4.98 months. Serum IL-10 and IFN-* levels were evaluated with ELISA. Serum IL-10 levels were significantly high before and after immunotherapy compared to controls. There was no difference in IFN-* levels before and after SIT compared to controls. According to this study, in patients with allergic rhinitis after immunotherapy serum IL-10 levels are decreased but IFN-* no change.

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.

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.

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.