A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

The mediator role of treatment response on oral health related quality of life in Behçet's syndrome.

BACKGROUND: The aim of the study was to analyse the effects of Treatment Response with oral ulcers on oral health related quality of life in Behçet's syndrome (BS). MATERIAL AND METHODS: In the cross-sectional study, 339 BS patients (F/M: 179/160, mean age: 36,13±9,81 years) were included. Data were collected by clinical examinations and patient reported outcome measures (PROMs) regarding Oral Health Impact Profile-14 (OHIP-14) questionnaire and self-reported Treatment Responses coded by a 5-point Likert-type scale (1: symptoms were cured- 5: symptoms were worsened). Moderated Mediation analysis (MA) was used to understand how oral ulcer activity (independent variable; X) influenced OHIP-14 score (outcome variables, Y) through self-reported Treatment Response (M1) and age (M2) as possible mediator variables (M) and disease course (mucocutaneous and musculuskeletal involvement vs. major organ involvement) as a possible moderator variable (W) on these relationships. RESULTS: In Moderated MA, OHIP-14 score (Y) was mediated by the presence of oral ulcer (X) (p=0.0000), the negative Treatment Response (M1) (p=0.0001) and being young (M2) (p=0.0053) with mucocutaneous involvement (W)(p=0.0039). CONCLUSIONS: Self-reported Treatment Response as an underestimated issue has a Mediator role in relation to oral ulceration on oral health related quality of life in the framework of patient empowerment strategies. Therefore, study results give clues to assist physicians and dentists for better understanding of patients' perspective.

The prevalence of non-vascular pulmonary manifestations in Takayasu's Arteritis patients: A Retrospective multi-centred Turkish cohort study.

OBJECTIVES: Takayasu's arteritis (TAK) is a rare vasculitis characterized by inflammation of intermediate- to large-size arteries. Although pulmonary artery involvement (PAI) is an expected finding in some TAK patients, data on non-vascular pulmonary involvement (NVPI) are limited. We aimed to investigate the frequency of NVPI, including parenchymal infiltration, nodules/cavities, pleural effusion, and haemorrhage, in TAK. METHOD: We assembled a retrospective cohort of TAK patients from nine tertiary centres in Turkey. The demographics and clinical characteristics of patients were extracted from medical records and the imaging findings were evaluated for pulmonary manifestations. RESULTS: As of January 2021, 319 TAK patients (female/male 276/43; mean age 42.4 ± 13.5 years) were recruited. Eighty-two patients had cough and/or dyspnoea and four had haemoptysis as pulmonary symptoms. On computed tomography assessment, the overall frequency of NVPI was 7.2%; parenchymal infiltrations were present in 10 (3.1%), pleural effusion in eight (2.5%), nodules/cavities in six (1.9%), and pulmonary haemorrhage in four patients (1.3%). In the whole cohort, 10.3% of patients had pulmonary artery hypertension (PAH) and 5.6% had PAI. Among patients with PAH or PAI, the overall frequency of NVPI was significantly higher than in the rest of the group. CONCLUSIONS: In this TAK cohort from Turkey, we observed NVPI in 7.2% of patients, with parenchymal infiltrations being the most common, followed by pleural effusion. Notably, NVPI was more frequent in patients with PAH or PAI. Although not as common as PAI, NVPI should be kept in mind, especially in TAK patients with PAH or PAI.

Fatigue in systemic lupus erythematosus : Association with disease activity, quality of life and psychosocial factors.

OBJECTIVE: The aim of the study was to determine which disease-related factors and non-disease features can explain the presence of systemic lupus erythematosus (SLE)-related fatigue in Turkish patients. METHODS: This cross-sectional study was carried out with 99 SLE patients and 71 healthy controls. To assess fatigue and health-related quality of life (HRQoL) the participants were asked to complete two questionnaires: the short form-36 health survey (SF-36) and the multidimensional assessment of fatigue (MAF) scale. Anxiety and depression of participants were assessed by the hospital anxiety and depression scale (HADS). RESULTS: A total of 99 patients (female/male 95/4) and 71 controls (female/male 40/31) were studied. The mean age and standard deviation (±SD) of patients and controls were 43.3 ± 12.2 years and 43.2 ± 12.1 years, respectively. The mean (SD) disease duration was 7.8 ± 5.3 years and median SLE disease activity index (SLEDAI) score was 0 (range = 0-16). The level of fatigue was higher in patients compared to controls with mean MAF scores of 24.7 ± 12.2 and 12.8 ± 9.9 (p < 0.001), respectively. The HADS-D and HADS-A scores were also significantly higher in SLE patients (6.6 ± 4.3 vs. 3.6 ± 2.9, p < 0.001 and 7.2 ± 4 vs. 4.9 ± 4, p = 0.007, respectively). There were no significant associations between the MAF and SLEDAI scores (r = 0.05, p = 0.63) but MAF scores positively correlated with age, HADS-A and HADS-D scores and negatively correlated with physical component summary (PCS), mental component summary (MCS) and each domain of SF-36 except role emotional in SLE patients. CONCLUSION: Fatigue is an important factor influencing patient daily life independent from disease activity in our study. The SLE patients with severe fatigue should also be assessed for other possible underlying causes such as anxiety, depression and poor quality of life.

Risk factors for malignancy in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multisystem involvement. An increased incidence of cancer in SSc patients compared with the general population has been reported in several reports. Our aims in this study were to determine the most common malignancies and to investigate the possible risk factors for the development of malignancy in patients with SSc. Three hundred forty SSc patients from 13 centers were included to the study. Data of the patients were obtained by evaluating their medical records retrospectively. A total of 340 patients with SSc were evaluated. Twenty-five of the patients had 19 different types of malignancy. Bladder cancer was the most common type of cancer with four patients and was followed by breast cancer with three patients, and cervix cancer and ovarian cancer with two patients each. Other types of cancers such as squamous cell skin cancer, adenocancer with an unknown origin, multiple myeloma, chronic myeloid leukemia, papillary thyroid cancer, larynx cancer, non-small cell lung cancer, follicular type non-Hodgkin lymphoma (NHL), endometrium cancer, colon cancer, uterus cancer, neuroendocrine tumor, glioblastoma multiforme, and soft tissue sarcoma were diagnosed in one patient each. The only cancer type that showed an association with cyclophosphamide dose was bladder carcinoma. Other malignancies did not show a correlation with age, sex, smoking, type and duration of the disease, autoantibodies, organ involvement, and dose and duration of cyclophosphamide therapy. Cancer may develop in any organ in patients with SSc. Continuous screening of the patients during a follow-up period is necessary for the early detection of the tumor development.

Activation of the JAK/STAT pathway in Behcet's disease.

Th1/Th17-type T-cell responses are upregulated in Behcet's disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using messenger RNA of isolated CD14(+) monocytes and CD4(+) T cells from peripheral blood mononucleated cell (PBMC) in patients with BD (n = 9) and healthy controls (HCs) (n = 9). Flow cytometric analysis of unstimulated (US) and stimulated (phytohaemagglutinin) signal transducer and activator of transcription (STAT3) and pSTAT3 expressions of PBMCs were also analyzed (BD and HC, both n = 26). Janus family of kinase (JAK1) was observed to be upregulated in both CD14(+) monocytes (1.95-fold) and CD4(+) T lymphocytes (1.40-fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14(+) monocytes (P = 9.55E-03) and in CD4(+) lymphocytes (P =8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14(+) monocytes (P = 5.62E-05). Glucocorticoid receptor signaling and interleukin (IL-6) signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (P = 2.45E-09 and 1.00E-06, respectively). Basal US total STAT3 expression was significantly higher in BD (1.2 vs 3.45, P < 0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, interferon (IFN-γ), IL-6, IL-17 and IL-23.

Familial Mediterranean fever gene (MEFV) mutations and disease severity in systemic lupus erythematosus (SLE): implications for the role of the E148Q MEFV allele in inflammation.

OBJECTIVE: Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients. MATERIAL AND METHOD: The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis. RESULTS: None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis (p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04-16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69-197.13). CONCLUSIONS: Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature. In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.

Serum cytokine profiles in Takayasu's arteritis: search for biomarkers.

OBJECTIVES: Assessment of disease activity is one of the major difficulties in patients with Takayasu arteritis (TAK) during follow-up. To date, no biomarker is universally accepted to be a surrogate for active disease in TAK. In this study, we aimed to investigate levels of various pro-and anti-inflammatory molecules including serum granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, IL-10, IL-18 and IL-23 in patients with TAK. METHODS: The study included 51 patients (age: 40.6±12.2 years, F/M: 45/6) with TAK and 42 age- and sex-matched healthy controls (age: 38.1±7.4 years, F/M: 38/4). All patients fulfilled the criteria of the American College of Rheumatology (ACR). TAK patients were evaluated by physician's global assessment (PGA; active/inactive) and ITAS2010 (Indian Takayasu Arteritis Clinical Activity Score) in terms of clinical activity in baseline and follow-up visits. Commercial enzyme linked immuno-sorbent assay (ELISA) kits were used for measurements of serum cytokine levels. RESULTS: At baseline, 21 (41.2%) patients were active according to PGA and 8 (15.7%) according to ITAS2010. Serum IL-6, IL-8 and IL-18 levels were significantly higher in patients with TAK, whereas GM-CSF, IL-10, IL-23 levels were similar to healthy controls. IL-8 significantly decreased in the follow-up, associated with a decrease of clinical activity, whereas IL-23 level significantly increased. When assessed by ITAS2010 active patients had significantly higher IL-18 levels. CONCLUSIONS: We found significantly increased IL-6, IL-8 and IL-18 levels in patients with TAK compared to healthy controls. Only IL-18 level was significantly higher in active patients assessed by ITAS2010. IL-18 was also the only cytokine in our study that correlated with CRP. These findings suggest that cytokines associated with neutrophilic, pro-inflammatory responses such as IL-6, IL-8 and IL-18 can be potential biomarkers for the assessment of disease activity in TAK and warrant further studies in larger series.

Right ventricular and atrial functions in systemic sclerosis patients without pulmonary hypertension. Speckle-tracking echocardiographic study.

BACKGROUND: Systemic sclerosis (SSc) is a systemic connective tissue disease and cardiac involvement is one of the most important causes of death. Right ventricular (RV) systolic dysfunction is a poor prognostic finding in SSc patients. Assessment of RV function has some difficulties because of its crescent shape and extensive trabeculations. Two-dimensional (2D) speckle-tracking echocardiography (STE) is an angle-independent quantitative technique to evaluate myocardial function. The aim of this study was to assess the RV and right atrial (RA) functions of SSc patients without pulmonary hypertension by using 2D STE. PATIENTS AND METHODS: A total of 40 patients with SSc (mean age 48.5 ± 11.4 years, 28 female) and 40 healthy volunteers (mean age 45.9 ± 7.6 years, 21 female) were included in the study. All subjects underwent transthoracic echocardiography for evaluation of RV and RA functions with 2D STE. RESULTS: Although left ventricular systolic and diastolic functions, systolic pulmonary artery pressure (PAP), and RA measurements were similar in both groups, tricuspid annular plane systolic excursion (TAPSE) and maximum systolic myocardial velocity (S') were decreased in SSc patients. The RV free wall global longitudinal strain (GLS) of SSc patients was lower than the controls (- 18.5 ± 4.9 % vs. - 21.8 ± 2.4 %, p < 0.001) and the RA reservoir and conduit functions were also decreased in SSc patients compared with controls (34.4 ± 9.9 % vs. 39.7 ± 11.2 %, p = 0.027 and 15.0 ± 5.7 % vs. 18.7 ± 6.4 %, p = 0.009, respectively). Disease duration was inversely correlated with RVGLS and TAPSE (r: - 0.416, p = 0.018 and r: - 0.383, p = 0.031, respectively). CONCLUSION: The use of 2D STE can be helpful in the detection of impairment in RV and RA functions in SSc patients with normal PAP.

Ankylosing spondylitis and a diagnostic dilemma: coccydynia.

OBJECTIVES: Coccydynia is defined as pain in or around the tail bone area. The most common cause of coccydynia is either a trauma such as a fall directly on to the coccyx or repetitive minor trauma. The etiology remains obscure in up to 30% of patients. The literature on the contribution of rheumatic diseases to coccydynia is scarce. Our objective was to investigate the prevalence of coccydynia in ankylosing spondylitis (AS) patients. METHODS: One hundred and seven consecutive patients with AS were evaluated for coccydynia were enrolled between January and November 2012 for a cross-sectional analysis. Seventy-four consecutive patients were followed for mechanical back pain as controls and the AS patients were interviewed for the presence of coccydynia. The data collected was evaluated on SPSS® version 11.5 and Microsoft Excel® Programmes. RESULTS: Prevalence of coccydynia in AS (38.3%) was significantly higher than the control group (p<0.0001) in both female and male AS patients (female AS vs. control=40.9% vs. 18.4%, p=0.015 and male AS vs. control=36.5% vs. 8.0%, p=0.005). Both genders were affected equally in the AS group whereas coccydynia was slightly more frequent in female patients in the control group. CONCLUSIONS: Coccydynia is a previously neglected symptom of AS and it is almost three times more common in AS than in non-specific chronic low back pain. Our observation may implicate that inflammatory diseases have a role in the etiology of coccydynia, especially in those without a history of recent or past trauma and coccydynia may be a factor associated with the severity of AS as well.

Innate and Adaptive Responses to Heat Shock Proteins in Behcet's Disease.

Behcet's disease (BD) is a systemic, chronic inflammatory disorder with both innate and adaptive immune responses. Heat shock proteins (HSP) are highly conserved molecules in different species with scavenger activity and involved in correct folding of newly synthesized proteins. T and B cell responses against HSPs are observed in BD patients in both αß and γδ T-cell populations. 60-kD HSP (HSP60) is also shown to be recognized by pattern recognition receptors such as toll-like receptors (TLR) and is suggested to be an endogenous "danger" signal to the immune system with rapid inflammatory cytokine releases and enhancement of adaptive Th1-type responses. Elucidating the exact role of HSPs in BD pathogenesis might pave the way to less toxic therapeutic approaches to BD, such as antibacterial therapies and immunomodulation.

Effect of vitamin D deficiency and replacement on endothelial functions in Behçet's disease.

OBJECTIVES: Endothelial dysfunction is previously demonstrated in Behçet's disease (BD) and vitamin D is implicated to affect endothelial functions. We aimed to evaluate the status of serum 25(OH)Vit D3 levels and its association with disease activity, endothelial function and carotis intima media thickness (CIMT) in patients with BD. METHODS: Thirty-six BD (F/M: 22/14, mean age: 39.6 years) patients and 51 healthy controls (F/M: 28/23, mean age: 34.5 years) were studied. Rheumatoid arthritis (RA) (n=33) patients (F/M: 26/7, mean age: 50.82 years) were also enrolled, as a disease control group. Endothelial function was evaluated by brachial artery flow mediated dilatation (FMD) and CIMT with B-Mode ultrasound. The vitamin D-deficient BD patients received 1000 IU Vitamin D3 daily for 3 months. RESULTS: Less than 50 nmol/L levels of 25(OH) Vit D3 were present in 61.1% (n=22) of BD and 35.3% (n=18) of HC (serum 25(OH)Vit D3 levels: BD: 44.5 (9-112) vs HC: 56 (14-125) nmol/lt, p=0.01). CIMT and FMD were also significantly different between BD and HC [0.56 (0.35-9.26) vs. 0.39 (0-0.52) and 5.20 (0.56-30.58) vs. 9.04 (-6.9-34.17), p=0.001 and p=0.02, respectively]. However, no correlation was observed between 25(OH)VitD3 levels and CIMT or FMD (r=0.6, p=0.7 and r=0.03, p=0.8, respectively) at baseline. CIMT measurements improved after replacement therapy (0.56 vs. 0.49, p=0.02), FMD measurements also improved, but not reaching statistical significance (5.2 vs. 8.28, p=0.06). CONCLUSIONS: A high presence of vitamin D deficiency was observed in BD patients from Turkey and replacement of vitamin D had favourable effects on endothelial function.

Lack of association between IL-6 gene polymorphisms and rheumatoid arthritis in Turkish population.

Inflammatory cytokines play an important role in the pathogenesis of rheumatoid arthritis (RA). One of candidate genes is interleukin-6 (IL-6), and single-nucleotide polymorphisms in the promoter region of IL-6 were found to be associated with RA. The aim of this study was to determine the association between IL-6 promoter polymorphisms (-174, -572, -597) and RA in Turkish population. A total of 425 subjects were recruited into the study (247 healthy controls and 178 RA). The promoter region of IL-6 gene was amplified by PCR using DNAs from patients and the controls, and their PCR products were digested by suitable enzymes. No significant association was found between RA and -174 genotype distribution (P = 0.535) and allele frequency (P = 0.230). There was also no relationship between -572 (P = 0.150) and -597 (P = 0.912) gene polymorphism and RA. Our results suggested that IL-6 gene promoter polymorphisms have no association with RA in Turkish population.

Comparison of QuantiFERON-TB Gold test and tuberculin skin test for the identification of latent Mycobacterium tuberculosis infection in lupus patients.

UNLABELLED: The tuberculin skin test (TST) has low sensitivity for the diagnosis of tuberculosis (TB). QuantiFERON-TB Gold (QFT-G) is an IFN-gamma-release assay that measures the release of interferon-gamma after stimulation in vitro by Mycobacterium tuberculosis antigens using ELISA. The main advantage of this assay compared with TST is the lack of cross-reaction with Bacillus Calmette-Guérin (BCG) as well as most of non-tuberculous mycobacteria. The aim of our study is to compare QFT-G with TST for the detection of latent tuberculosis infection (LTBI) among patients with systemic lupus erythematosus (SLE). METHODS: Seventy-eight patients with SLE and 49 healthy subjects (HCs) participated in the study. All patients and controls were interviewed for a history of TB then BCG vaccinations were recorded and chest X-rays were examined for a sign of TB infection. QTF-G and TST were performed on both patients and controls. QTF-G results were recorded as positive, negative or indeterminate. A positive TST for SLE was defined as ≥5 mm. RESULTS: Seventy-six SLE patients (97.4%) had been BCG vaccinated. Similar to the HC (28.5%), 19 of 78 (24.3%) SLE patients had positive QTF-G. Two patients had an indeterminate result. The agreement between QTF-G and TST was 49/76 (64.4%) (κ = 0.33). There were fewer positive QFT-G test results than positive TST results (24.3% vs. 50%; p < 0.01). Twenty-two (28.9%) patients were TST(+)/QTF-G(-) while only 3(3.9%) patients were TST(-)/QTF-G(+). When the positive TST was defined as ≥10 mm indurations, which is the cut-off in screening for LTBI in Turkey, the agreement between two tests increased up to 58/76 (76.3%) with a κ value of 0.47. The mean TST measurements was higher in QTF-G positive patients (13.4 ± 8.8 mm) than the QTF-G negative patients (4 ± 5.3 mm) (p < 0.001). DISCUSSION: In a TB-endemic and BCG vaccinated population, the QuantiFERON-TB Gold assay seemed to be a more accurate test for the detection of LTBI in SLE patients. Although 5 mm is usually accepted to be the standard cut-off for TST in immunocompromised patients such as SLE, the level of agreement between QTF-G and TST was better with a 10 mm cut-off in our population.

Active disease requiring TNF-alpha-antagonist therapy can be well discriminated with different ASDAS sets: a prospective, follow-up of disease activity assessment in ankylosing spondylitis.

OBJECTIVES: To evaluate the validity of different ASDAS sets to assess disease activity in ankylosing spondylitis (AS) in comparison to standard activity assessment tools in routine clinical setting and to determine the best cut-off values for deciding active disease requiring TNF-α antagonist therapy. METHODS: Two hundred consecutive AS patients (M/F:104/96) were enrolled. Mean (SD) age was 40.3 (11.7) and disease duration was 11 (8.5) years. Disease activity was assessed by four different ASDAS sets, BASDAI, patient and physicians' global assessments, ESR and CRP. The correlation between different parameters and ASDAS scores of patients requiring TNF-α antagonist therapy were determined. RESULTS: At the time of the assessment 18.5% of the patients were only having NSAIDs, 43% were receiving sulphasalazine and/or methotrexate and 38.5% were under TNF-α antagonists. After the evaluation, 36 (18%) patients were decided to require TNF-α antagonist therapy, 33 (16.5%) patients were started sulphasalazine or methotrexate or their dose increased and 131 (65.5%) patients were decided to be stable without any requirement for a change in therapy. The patients requiring new-TNFα antagonist therapy had significantly higher ASDAS values. The ROC curve analysis revealed best-cut off values for ASDAS sets (ASDAS A: 3.28, ASDAS B: 3.07, ASDAS C: 2.38 and ASDAS D: 3.1) When standardised mean differences were compared, ASDAS B was the best set within the others, but not significantly different from other ASDAS sets and standard assessment tools except acute-phase reactants. CONCLUSIONS: ASDAS sets perform well to discriminate TNF-α antagonist requirement in advanced AS patients. However BASDAI and patient's or physician's global assessments also had acceptable performances in our clinical setting.

The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide.

OBJECTIVE: To update the follow-up of the Euro-Lupus Nephritis Trial (ELNT), a randomised prospective trial comparing low-dose (LD) and high-dose (HD) intravenous (IV) cyclophosphamide (CY) followed by azathioprine (AZA) as treatment for proliferative lupus nephritis. PATIENTS AND METHODS: Data for survival and kidney function were prospectively collected during a 10-year period for the 90 patients randomised in the ELNT, except in 6 lost to follow-up. RESULTS: Death, sustained doubling of serum creatinine and end-stage renal disease rates did not differ between the LD and HD group (5/44 (11%) vs 2/46 (4%), 6/44 (14%) vs 5/46 (11%) and 2/44 (5%) vs 4/46 (9%), respectively) nor did mean serum creatinine, 24 h proteinuria and damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. After 10 years of follow-up, the positive predictive value for a good outcome of an early drop in proteinuria in response to initial immunosuppressive therapy was confirmed. CONCLUSION: The data confirm that a LD IVCY regimen followed by AZA-the "Euro-Lupus regimen"-achieves good clinical results in the very long term.

Association of salivary S. mutans colonisation and mannose-binding lectin deficiency with gender in Behçet's disease.

OBJECTIVE: The present study aimed to investigate the interactions among salivary S. mutans colonisation, serum mannose binding lectin level (MBL), oral ulcer activity and disease course in patients with Behçet's disease (BD). METHODS: One hundred and six BD patients, 25 patients with rheumatoid arthritis (RA) and 42 healthy controls (HC) were included in the study. BD patients were grouped as active (n=52) or inactive (n=54) according to oral ulcer status of the previous 3 months. Salivary colonisation of S. mutans levels were investigated by standard Caries Risk Test (CRT) Bacteria kits (Ivoclar, Vivadent). S. mutans colonies were categorized as high (> or =10(5) colony forming unit (CFU)/ml of saliva) or low (10(5)CFU/ml). Serum mannose binding lectin (MBL) levels were measured by ELISA. RESULTS: High levels of salivary S. mutans colonisation was significantly more present in BD (50%) than HC (28.6%)(p=0.039), whereas no significant difference was observed between RA and other groups (p>0.05). S. mutans presence in saliva was associated with oral ulcers (61.5% in patients with active oral ulcers vs 38.9% in inactives) (p=0.020). S. mutans colonisation in saliva was significantly higher among male BD patients with a severe disease course than a milder disease (p=0.04). Increased salivary S. mutans colonisation was also related to very low serum MBL (<100 ng/ml) in BD compared to controls (p=0.04). CONCLUSION: The relationship between increased presence of S. mutans and MBL deficiency with active disease pattern may indicate an impaired innate immune response in BD patients which may predispose to oral infections and a severe disease course.