Clinical Parameters Of Disease Activity Research Articles

Increased interleukin-23 is associated with increased disease activity in patients with rheumatoid arthritis

Background Interleukin-23 (IL-23) is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration of IL-23 is elevated in patients with rheumatoid arthritis (RA), and to determine the relationship between the IL-23 level and disease activity in RA patients. Methods Serum samples were obtained from 59 patients with RA and 30 healthy controls. The clinical parameters of disease activity were determined, including the 28-joint disease activity score (DAS28), C-reactive protein (CRP), rheumatoid factor (RF) levels, and the degree of bony erosions based on X-rays. The levels of IL-23 and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA). The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Results The serum IL-23 level was significantly elevated in patients with RA compared to healthy controls. The serum IL-23 levels in the RA patients correlated with IL-17 and CRP levels, and the DAS28. The levels of IL-23 based on X-ray classification phase I, II, III, and IV were gradually elevated in RA patients. Conclusions The levels of serum IL-23 in RA patients were higher than in healthy controls. Thus, elevated serum IL-23 levels may be useful markers to detect active RA. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA.

Increased production of IL-5 and dominant Th2-type response in airways of Churg–Strauss syndrome patients

Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with eosinophilia and asthma. We assessed the local immune response in airways of CSS patients with different activity of the disease. Concentration of IL-5, CCL17, CCL22 and CCL26 (ELISA) together with cell expression of T-helper-related genes (real-time PCR array) were measured in bronchoalveolar lavage fluid (BALF) sampled from 11 patients with active CSS, 11 patients with CSS in remission and 9 control subjects with bronchial asthma. In active CSS, both BALF and blood eosinophil counts were increased (P<0.01). BALF cells in active disease were characterized by an increased expression of Th2 and regulatory-type transcripts: STAT6, STAT3, GATA3, IL4, IL5 and IL10 as compared with asthmatics, and STAT5A, CCR4, FOXP3, IL4, IL5 and IL10 when compared with inactive CSS. There was significant increase in BALF concentration of IL-5 and CCL26 in exacerbation of CSS. CCR4-active chemokines were detected more frequently in active disease. We found a strong positive correlation between clinical parameters of disease activity (BVAS, eosinophilia) and expression of IL4, IL5, IL10 and STAT5A. These results indicate that as compared with asthma, active-CSS patients have much stronger local Th2 response in the airways. Airway cells may contribute to lung eosinophilia in CSS by producing IL-5 and eosinophil active chemokines.

Sarcoidosis-associated fatigue

Sarcoidosis-associated fatigue is globally recognised as a disabling symptom. Fatigue has been reported in up to 50-70% of sarcoidosis patients, causing impaired quality of life. The aetiology of this troublesome problem remains elusive and is usually multifactorial. Fatigue can be a consequence of treatment itself, including as a complication of corticosteroid therapy. The diagnosis of sarcoidosis-associated fatigue requires an extensive evaluation to identify and treat potentially reversible causes. Granuloma formation and cytokine release may be involved in its aetiology. However, despite adequate sarcoidosis treatment, many patients continue to experience fatigue. Comorbidities associated with sarcoidosis, including depression, anxiety, hypothyroidism and altered sleep patterns, may all contribute to fatigue. Despite an exhaustive search for treatable clinical causes of fatigue, most patients' complaints of fatigue are not correlated with clinical parameters of disease activity. Recent studies have demonstrated the effectiveness of various neurostimulants, including methylphenidate, for the treatment of sarcoidosis-associated fatigue. These and other agents may be useful adjuncts for the treatment of sarcoidosis-associated fatigue. Obviously, there is a need for studies evaluating the causes and new therapeutic options of sarcoidosis-associated fatigue. Psychological interventions should also be examined.

Cytokines as Immunological Markers for Follow up of Disease Activity During the Treatment of Pulmonary Tuberculosis

Background : Cytokines play a major role in protection against Mycobacterium tuberculosis infection and regulate the immune responses at a cellular level. Cytokine profile determines clinical outcome of the disease and responses to treatment as well. A T helper 1 (Th1) cytokine interferon gamma (IFN-U) is one of the most important cytokines which activate the macrophages to produce tumor necrosis factor-alpha (TNF-V). Excessive production of TNF-V have been implicated in immunopathogenesis of tuberculosis. A T helper 2 (Th2) response leads to release of IL-4, and IL-10 promoting an anti-inflammatory macrophage response. Interleukin-4(IL-4), has been implicated to down-regulate IFN-U, and thus has a harmful effect on TB patients. IL10 cytokine has the capacity to inhibit Th1 activation and thus terminates cell mediated immune responses. Objective :The objective of the present study was to determine Th1 and Th2 cytokine profile in patients with tuberculosis to identify immunological marker for follow up of the disease activity, and to study the outcome of treatment. Methods : To examine this, blood samples were collected from newly diagnosed HIV negative pulmonary tuberculosis patients and from apparently healthy individuals as controls following an informed consent. Blood samples were as well collected at several intervals during the treatment with anti-tuberculosis drugs. Levels of IFN-U, TNF-V, IL-4 and IL-10 were measured pre and during treatment using commercial available enzyme-linked immune-sorbent assay (ELISA). Data were analyzed using SPSS 20. Receiver Operating Characteristic (ROC) Curve analysis has been carried out to assess their discriminative power and to determine cut-off values. Analysis has been carried out further by calculating other measures of diagnostic test accuracy. Results : The median serum level of IL-4 was 20 and 35 pg/ml higher in new cases (untreated patients) and in patients under treatment with oral anti-tuberculosis, respectively, compared with that of controls (p=001). Levels of TNF- were significantly increased in patients before and after the treatment than those in control (p=0.001). New cases had the highest median level (10pg/ml) followed by those under treatment group (6pg/ml). Levels for IFN-U were not statistically different between patients and controls (p=0.351). Median levels of IL10 were similar in both controls and new cases groups (35pg/ml), but lower in patients under treatment group (20pg/ml). Increase in levels of IL-4 during treatment showed that Th2 immune responses still present and may indicate active disease and thus IL4 cytokine may be a possible marker for the disease activity. Conclusion : serum levels of TNF- in TB patients is useful in the evaluation of the disease activity during therapy, not replacing clinical parameters of disease activity in TB. Similar to TNF-, IL-4 can also be used as marker for TB severity. On the other hand IL-4test can be used to diagnose TB in highly exposed suspects where a positive result is more likely to indicate TB. Keywords : Tuberculosis; Cytokines; Immunological markers.

Disease activity score-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis: data from the GUEPARD trial and ESPOIR cohort

ObjectivesTo compare the efficacy of disease activity score in 28 joints (DAS28ESR)-driven therapy with anti-tumour necrosis factor (patients from the GUEPARD trial) and routine care in patients with recent-onset rheumatoid...

The Correlation between Increased Serum Concentrations of Interleukin-6 Family Cytokines and Disease Activity in Rheumatoid Arthritis Patients

PurposeThis study was performed to determine whether the serum concentrations of interleukin (IL)-6 family cytokines are elevated in patients with rheumatoid arthritis (RA) and to investigate the relationship between IL-6 family cytokine levels and disease activity in RA patients.Materials and MethodsWe obtained serum samples from 40 patients with RA and 40 age- and sex-matched healthy controls, and we assessed the clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP) levels. Serum samples from five patients with high disease activity (DAS28 > 5.1) were also collected at the eighth week of treatment. Serum concentrations of IL-6, IL-11, and leukemia inhibitory factor (LIF) were measured using an enzyme-linked immunosorbent assay (ELISA).ResultsSerum concentrations of IL-6 family cytokines, including IL-6, IL-11, and LIF, were significantly elevated in patients with RA compared to those of healthy controls. Although there was no significant relationship between IL-6 family cytokine levels and DAS28, the IL-6 levels of patients with RA showed a significant correlation with CRP levels. After eight weeks of medical treatment in patients with high disease activity, a decrease in DAS28 was associated with a significant decrease in the serum concentrations of IL-6 and IL-11.ConclusionThe serum concentrations of IL-6 family cytokines were significantly elevated in patients with RA, and they decreased with medical treatment. These findings suggest a possible role for IL-6 family cytokines in the pathogenesis of RA.

Comparison of a high sensitivity and standard C reactive protein measurement in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis

ObjectiveThis study was aimed at comparing high sensitivity C reactive protein (hsCRP) measurement with routine C reactive protein (CRP) evaluation as disease activity parameters in patients with ankylosing spondylitis (AS)...

Towards a multidimensional patient reported outcome measures assessment: Development and validation of a questionnaire for patients with ankylosing spondylitis/spondyloarthritis

ObjectiveTo assess the validity, reliability and responsiveness to change of a patient self-reported questionnaire that can assess construct outcome measures of patients with ankylosing spondylitis (AS)/spondyloarthritis. MethodsThe questionnaire was developed by integrating information obtained from patients suffering from AS/spondyloarthritis based on the Rasch model. The questionnaire includes assessment of functional disability, quality of life, VAS for spinal pain, joint pain, global status, fatigue, duration of morning stiffness, review of the systems, falls and cardiovascular risks, self-helplessness as well as self-reported joint and soft tissue pain. The questionnaire was completed by 267 consecutive patients with AS (124) and spondyloarthritis (143). ResultsThe PROMs questionnaire was reliable as demonstrated by a high-standardized alpha. The questionnaire items correlated significantly (p<0.01) with clinical parameters of disease activity. Patient reported tender joints and enthesitis scores correlated significantly with the physician's scores (correlation coefficient 0.848 and 0.821 respectively). Changes in functional disability, quality of life as well as self-helplessness scores showed significant (p<0.01) variation with diseases activity status. The PROMs questionnaire showed also a high degree of comprehensibility (9.3). ConclusionThe developed PROMs questionnaire is a reliable and valid instrument for assessment of patients suffering from AS and spondyloarthritis. Being short, rapid and comprehensive, this adds more to its applicability. The data support the value of completion of the simple two pages patient questionnaire, which provides a quantitative written documented record by the patient, at each visit to the rheumatologist.

Effect of etanercept and entecavil in a patient with rheumatoid arthritis who is a hepatitis B carrier: a review of the literature

In this report, we describe a case of a 48-year-old Japanese woman who is a hepatitis B (HB) carrier with rheumatoid arthritis (RA). She had the following antibody profile: HBs Ag(+), HBs Ab(-), HBe Ag(-), HBe Ab (+), HBc Ab(-) and undetectable HBV-DNA level. She was treated with auranofin, salazosulfapyridine, and bucillamine. Finally, she was treated with D: -penicillamine, but her disease activity remained elevated. Prophylactic treatment of entecavir 0.5 mg daily was started in March 2008 and all disease-modifying anti-rheumatic drugs were stopped. After 2 weeks, etanercept monotherapy was started at 25 mg subcutaneously once a week. Significant improvement in clinical parameters of disease activity and well being was observed. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and HB virus viral load did not change significantly. Serum ALT, AST, and HB virus viral load were followed-up at every 3-month intervals, from initiation of therapy up to 24 months after the start of treatment with etanercept. We have also summarized the course of nine RA patients who received etanercept and were HB carriers or had chronic HB according to our literature search. Based on the results of our study, treatment of these patients with etanercept co-administered with lamivudine or entecavir appears to be safe.

Validity of the Developed Arabic Multidimensional Health Assessment Questionnaire for use in standard clinical care of patients with rheumatic diseases

AbstractObjective: To assess the validity, reliability and comprehensibility of the Developed Arabic Multidimensional Health Assessment Questionnaire (Arabic‐MDHAQ) for use in standard clinical care of patients with rheumatic diseases.Methods: The multidimensional questionnaire was developed on a one‐page sheet. One side includes 10 activities of daily living (Arabic HAQII), four items to assess psychological distress, duration of morning stiffness as well as visual analogue scales for pain, global status, and fatigue. The other side includes review of the systems, falls and cardiovascular risk assessment, the rheumatology attitudes index to assess the psychological construct of helplessness and self‐report of joint counts. The questionnaire was completed by consecutive patients with various rheumatic diseases including 85 with rheumatoid arthritis, 57 with fibromyalgia, 57 with osteoarthritis, 18 with psoriatic arthritis and 11 with ulcerative colitis.Results: The test was reliable as demonstrated by a high standardized alpha‐value and minimal changes recorded in the second from the first test. The Developed Arabic‐MDHAQ correlated significantly with clinical parameters of disease activity as well as inflammatory markers. Changes in both functional and psychological assessment scores showed variation with diseases. The Arabic health assessment questionnaire II (functional disability) was significantly correlated with the original Arabic‐HAQ. The psychological assessment items in the Arabic‐MDHAQ were significantly correlated with depression as well as anxiety scores as demonstrated by Hamilton scales for depression and anxiety (P &lt; 0.001). The Arabic‐MDHAQ showed also a high degree of comprehensibility (92.9%).Conclusion: The Developed Arabic‐MDHAQ is a reliable and valid instrument for assessment of Arabic patients suffering from rheumatic diseases. Being short, rapid and comprehensive, this adds more to its applicability. The data support the value of completion of the simple 2‐page patient questionnaire, which provides a quantitative written documented record by the patient, at each visit to a rheumatologist.

Quantitative assessment of synovitis in juvenile idiopathic arthritis using Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Methods In 22 JIA patients 12 wrists and 10 hips were studied with DCE-MRI. A 3D FFE Dynamic sequence was acquired after contrast injection. Two readers delineated independently a region of interest (ROI) in the area of maximal synovial enhancement. Enhancement curves were obtained plotting pixel intensity against time from the ROIs. Maximum level of synovial enhancement (ME), maximum rate of enhancement (MV) and rate of early enhancement (REE) were obtained from the curves. Correlations with clinical parameters of disease activity and with static MRI synovitis score were investigated.

Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with clinical disease activity measures

The factors that induce remission of RA during pregnancy and the relapse occurring after delivery remain an enigma. In a previous study, we investigated gene-expression profiles of peripheral blood mononuclear cells (PBMC) in patients with RA and healthy women in late pregnancy and postpartum. Profiles of samples from both groups were similar in late pregnancy with elevated monocyte and decreased lymphocyte signatures. Postpartum, in RA PBMC the high level of monocyte transcripts persisted. Further increase was observed in adhesion, migration and signalling processes related to monocytes but also in lymphocytes despite similar clinical activity due to intensified drug treatment. This prompted us to investigate correlations between clinical parameters of disease activity and gene profiles. Transcriptome data were correlated with RADAI, CRP, monocyte and lymphocyte counts. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations, monocytes and lymphocytes signatures were used as reference information. Comparative analysis of PBMC expression profiles from RA patients during and after pregnancy with RADAI and CRP revealed a correlation of these disease activity parameters predominantly with monocyte transcripts. Genes related to cellular programs of adhesion, migration and response to infections were upregulated. Comparing clinically active and not-active RA patients postpartum revealed a cluster of 19 genes that could also identify active disease during pregnancy. The data suggest that an increase of the RADAI and an elevation of CRP is a consequence of molecular activation of monocytes. Furthermore, they indicate that molecular activation of T lymphocytes may remain clinically unrecognized postpartum. It is conceivable that a set of 19 genes may qualify as molecular disease activity marker.

Interferon-Beta-1a subkutan in der Behandlung der Multiplen Sklerose

During the last 10 years recombinant interferon-beta-1a administered subcutaneously has been the subject of several clinical trials in relapsing remitting multiple sclerosis (RRMS), in secondary progressive MS (SPMS), as well as in clinically isolated syndromes. All of them met the criteria of evidence level class I. Consistent evidence for moderate immunomodulatory effects on clinical parameters of disease activity was gained, and even higher efficacy of IFN-beta-1a sc. on MRI activity of multiple sclerosis was proven. Indirect evidence confirmed the hypothesis of a dose-response curve for IFN-beta-1a formulations in MS. The higher efficacy of IFN-beta-1a 44 microg sc. TIW, however, also includes more adverse events such as injection site reactions, flu-like symptoms and a moderate immunogenicity. Current evidence does not allow a recommendation of IFN-beta-1a sc. as most effective first line therapy, because also the individual patient's choice in the route of administration and long-term effects of neutralizing antibodies to IFN-beta-1a sc. must be taken into account. In the long-term, IFN-beta-1a showed a beneficial safety-tolerability profile with 50 % of patients sticking to the initial immunomodulatory treatment. There were no teratogenic effects, IFN-beta-1a sc. did not enhance depressive symptoms. Data on inhibition of the progression of disease, however, remained inconclusive. Probable beneficial effects of IFN-beta-1a sc. on cognitive function or "chronic fatigue" have not been investigated yet.

Is Osteoporosis Generalized or Localized to Central Skeleton in Ankylosing Spondylitis?

Osteoporosis at the lumbar spine and at the femur is a well-established complication in ankylosing spondylitis (AS), but the exact mechanism and the distribution of osteoporosis are not known absolutely. To determine whether the osteoporosis is generalized or localized to central skeleton and to examine the relation between bone mineral density (BMD) and disease activity and radiologic progression in patients with AS. In this study, 26 patients with AS and 33 healthy controls matched for age and sex were recruited to the study. Hip and forearm BMD were measured by dual energy X-ray absorptiometry (DEXA). Laboratory and clinical disease activity parameters were documented, and anteroposterior sacroiliac radiographs were taken to determine the radiologic progression. The urine deoxypyridinoline levels of the patients with AS were statistically significantly higher (P = 0.02) and the serum osteocalcin levels were significantly lower with respect to controls (P = 0.03). The femoral neck and femur BMD values and T scores were significantly lower in patients with AS compared with the controls (P = 0.019, 0.003, 0.01, and 0.01, respectively). The differences in BMD values and T scores of the distal 1/3 radius between 2 groups were not statistically significant. The relation between BMD and disease activity, and radiologic progression in patients with AS could not detected. Sparing of distal regions such as the as radius suggests that osteoporosis might be due to localized effects of inflammatory activity or immobility rather than a systemic effect. Both increased resorption and decreased formation might be involved in the pathogenesis of osteoporosis. Radius BMD may not be appropriate to evaluate bone loss in patients with AS.

Serum hyaluronan levels in patients with knee osteoarthritis

We examined the association between clinical parameters of disease activity and serum hyaluronic acid (HA) level in patients with knee osteoarthritis (OA). Fifty-eight patients with knee OA and 40 healthy individuals were included in this study. Demographic data were noted. The radiological evaluation was done according to Kellgren/Lawrence Grading System. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used in evaluating the clinical disability caused by OA. Erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level were determined in laboratory evaluations. Serum HA levels (in nanogram per milliliter) of both groups were measured by enzyme-linked immunosorbent assay. The mean ages of patients in OA group and control group were 57.58 (9.55) and 43.3(10.2) years, respectively. There was a significant difference between HA levels of both groups (p=0.02). Also, there was a significant correlation between HA level and disease duration (p=0.04), ESR (p=0.001), and CRP level (p<0.001). However, there was no significant correlation between HA levels with WOMAC and radiological grade (p>0.05). There is no satisfactory amount of data regarding HA level in OA. In our study, we demonstrated that HA was in high levels in the serum of patients with OA. We suggest that serum HA levels may be used as a marker to determine the disease activity.

Rapid improvement in rheumatoid arthritis patients on combination of methotrexate and infliximab: clinical and magnetic resonance imaging evaluation

The objectives of this study was to assess, using clinical and magnetic resonance imaging (MRI) criteria, the efficacy of combination infliximab therapy in patients with active rheumatoid arthritis (RA) refractory to methotrexate (MTX) treatment and to ascertain whether the changes in MRI parameters correlate with the clinical response. Four infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and 14 were added to a stable background dose of MTX in 19 patients with active disease. Clinical parameters were assessed before each infusion and at week 14. Dynamic contrast-enhanced MRI examination of the most severely affected wrist was performed at baseline and week 14. Synovitis severity, volume of synovitis, and synovial perfusion indices were evaluated. Significant improvement in all clinical disease activity parameters was seen at week 14 with reduction in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and DAS28. Sixty-eight percent of patients achieved ACR20. MRI disease activity parameters also significantly decreased after treatment with reduction in grading of synovitis, volume of active synovitis, and perfusion enhancement slope. Significant positive correlations were seen between the baseline volume of synovitis and the pain score (r=0.65), patient global score (r=0.68), and health assessment questionnaire (HAQ) score (r=0.46). In conclusion, addition of infliximab to methotrexate rapidly reduces inflammation in longstanding patients with RA. Assessment of enhancing synovial volume and perfusion indices on serial MRI examination was helpful in documenting the effect of treatment over this short period.

Quantitative morphometry of lupus nephritis: The significance of collagen, tubular space, and inflammatory infiltrate

Lupus nephritis encompasses a wide range of parenchymal injuries and severity. Better predictors of outcome are needed for patients newly diagnosed with lupus nephritis, so that an appropriate management strategy may be selected. A single-center cohort of first renal biopsies for lupus nephritis was chosen. Histologic sections of whole biopsy cores were stained with picro-Sirius red, and light microscopic images (x100) were digitally captured. Using a simple, freely available software package, the cortex of each biopsy was evaluated for four different parameters: area occupied by nuclei, intratubular space, fibrillary collagen, and collagenous matrix. Clinical and laboratory data were collected retrospectively from the time of biopsy and throughout follow-up. A high nuclear index at initial biopsy correlated with clinical parameters of disease activity, at the time of biopsy. High collagen matrix index predicted both relapse and progression to end-stage renal disease (ESRD). The fibrillary collagen index predicted progressive disease as assessed by doubling of serum creatinine, and relapse. Increased tubular space also predicted progressive disease as determined by doubling of creatinine and renal death. A simple automated system for objectively scoring biopsies of lupus nephritis predicts renal survival and may provide a useful adjunct to guide patient management.

関節リウマチ患者における血清マトリックスメタロプロテイナーゼ‐３（ＭＭＰ‐３）の臨床的意義

Matrix metalloproteinase-3 (MMP-3) is a proteolytic enzyme produced by synovial cells, participating in the joint destruction.To investigate the clinical significance of serum MMP-3 level in patients with rheumatoid arthritis (RA), we compared MMP-3 level with other clinical parameters of disease activity in 99 patients with RA. Sixty-two patients were positive for MMP-3. Both serum level of C-reactive protein (CRP) and the Lansbury articular index were significantly higher in the group of patients positive for MMP-3 compared to that of patients negative for MMP-3. Serum MMP-3 level was shown to be correlated with serum level of CRP and the Lansbury articular index, but not with tender joint count nor swollen joint count. Thus, our results strongly support the idea that serum MMP-3 level is a useful indicator of arthritic activity in patients with RA.

Anti-Saccharomyces cerevisiaeantibody titers are stable over time in Crohn’s patients and are not inducible in murine models of colitis

To investigate ASCA production over time in CD and murine colitis in order to further our understanding of their etiology. Sixty-six CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA positivity as well as change in titers over a period of up to 3 years (Delta IgG/A) was correlated with clinical parameters such as CD activity index (CDAI) and C-reactive protein levels (CRP). Moreover, two murine models of colitis (DSS and IL-10 knock out) were compared to control animals with respect to ASCA titers after oral yeast exposure. ASCA IgG and IgA titers are stable over time in CD and non-CD patients. Fistular disease was associated with a higher rate of ASCA IgA positivity (P = 0.014). Ileal disease was found to have a significant influence on the Delta IgG of ASCA (P = 0.032). There was no correlation found between ASCA positivity or Delta IgG/A and clinical parameters of CD: CDAI and CRP. In mice, neither healthy animals nor animals with DSS-induced or spontaneous colitis exhibited a marked increase in ASCA titers after high-dose yeast exposure. On the other hand, mice immunized intraperitoneally with mannan plus adjuvant showed a marked and significant increase in ASCA titers compared to adjuvant-only immunized controls (P = 0.014). The propensity to produce ASCA in a subgroup of CD patients is largely genetically predetermined as evidenced by their stability and lack of correlation with clinical disease activity parameters. Furthermore, in animal models of colitis, mere oral exposure of mice to yeast does not lead to the induction of marked ASCA titers irrespective of concomitant colonic inflammation. Hence, environment may play only a minor role in inducing ASCA.

Increased levels of interleukin-10 in saliva of Sjögren’s syndrome patients. Correlation with disease activity

The aim of the study was to determine the levels of interleukin (IL)-10, IL-2, IL-4, and interferon-gamma in the saliva of patients with Sjögren's syndrome and to correlate them with laboratory and clinical parameters of disease activity. The levels of IL-2, IL-4, IL-10, and interferon-gamma were measured in salivary samples, obtained directly from the Stenone duct of 14 Sjögren's syndrome patients and 26 healthy controls by ELISA. A significant elevation of IL-10 was found in salivary fluids of Sjögren's syndrome patients compared with healthy controls (P=0.007). Elevated interferon-gamma levels were found in some patients. IL-2 and IL-4 were undetectable in all saliva samples. In patients, IL-10 levels significantly correlated with the degree of xerophthalmia and xerostomia (P=0.02 and P=0.01, respectively) and with the erythrocyte sedimentation rate (P=0.006). Our data suggest that elevated IL-10 levels are detectable in the saliva of Sjögren's syndrome patients and correlate with the severity of the disease.