Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis.

OBJECTIVE: A 'mucosal connection' in RA presently attracts increasing attention. We recently described the occurrence of secretory antibodies to citrullinated protein (SC-ACPA) in sera from patients with recent-onset RA. The current study was performed to evaluate possible associations between serum levels of secretory ACPA and signs of lung involvement in patients with early, untreated RA. METHODS: One hundred and forty-two RA patients were included as part of the 'LUng Investigation in newly diagnosed RA' study. One hundred and six patients were examined with high-resolution CT (HRCT) and 20 patients underwent bronchoscopy, where bronchial biopsies and bronchoalveolar lavage fluid (BALF) samples were obtained. SC-ACPA in serum and BALF were detected by an enzyme-linked immunoassay. Antibody levels were related to smoking history, pulmonary function, HRCT, BALF cell counts and findings in bronchial biopsies. RESULTS: SC-ACPA occurred in 16% of the serum samples and in 35% of the BALF samples. SC-ACPA levels in serum correlated with SC-ACPA levels in BALF (σ = 0.50, P = 0.027) and were higher among patients with HRCT parenchymal lung abnormalities (P = 0.022) or bronchiectasis (P = 0.042). Also, ever smoking was more frequent among serum SC-ACPA-positive patients (91% vs 67%, P = 0.023), and the SC-ACPA levels correlated with the number of pack-years (σ=0.20, P = 0.020). CONCLUSION: In early, untreated RA, serum levels of SC-ACPA reflect lung involvement in terms of local ACPA levels, smoking and lung abnormalities on HRCT. These findings strengthen the link between mucosal ACPA responses and the lungs in RA.

Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk.

OBJECTIVES: Considering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain. METHODS: Two prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA. RESULTS: Serum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P < 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P < 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P < 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts. CONCLUSION: Serum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.

Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern.

OBJECTIVE: Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. METHODS: The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. RESULTS: There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (p<0.05).Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (p<0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. CONCLUSION: This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.

28-Joint count disease activity score at 3 months after diagnosis of early rheumatoid arthritis is strongly associated with direct and indirect costs over the following 4 years: the Swedish TIRA project.

OBJECTIVE: To explore possible association between disease activity at 3-month follow-up after RA diagnosis and costs over the following 4 years. METHODS: Three-hundred and twenty patients with early (≤ 1 year) RA were assessed at regular intervals. Clinical and laboratory data were collected and patients reported health-care utilization and number of days lost from work. At 3-month follow-up, patients were divided into two groups according to disease activity, using DAS-28 with a cut-off level at 3.2. Direct and indirect costs and EuroQol-5D over the following 4 years were compared between the groups. Multivariate regression models were used to control for possible covariates. RESULTS: Three months after diagnosis, a DAS-28 level of ≥ 3.2 was associated with high direct and indirect costs over the following 4 years. Patients with DAS-28 ≥ 3.2 at 3-month follow-up had more visits to physician, physiotherapist, occupational therapist and nurse, higher drug costs, more days in hospital and more extensive surgery compared with patients with 3-month DAS-28 < 3.2. Number of days lost from work due to sick leave and permanent work disability was also higher in this group. The effect of disease activity on health-related quality of life was highly significant. In regression models, DAS-28 at 3-month follow-up was significantly associated with costs over the following years. CONCLUSIONS: Three months after diagnosis, DAS-28 is an important prognostic marker regarding health-care utilization and costs. Achieving remission or low disease activity 3 months after diagnosis is likely to decrease morbidity, increase quality of life and save costs for the patient and for society over the following years.

Bone Erosions Detected by Ultrasound Are Prognostic for Clinical Arthritis Development in Patients With ACPA and Musculoskeletal Pain.

Anti-citrullinated protein antibodies (ACPA) often precede onset of rheumatoid arthritis (RA) by years, and there is an urgent clinical need for predictors of arthritis development among such at-risk patients. This study assesses the prognostic value of ultrasound for arthritis development among ACPA-positive patients with musculoskeletal pain. We prospectively followed 82 ACPA-positive patients without clinical signs of arthritis at baseline. Ultrasound at baseline assessed synovial hypertrophy, inflammatory activity by power Doppler, and erosions in small joints of hands and feet. We applied Cox regression analyses to examine associations with clinical arthritis development during follow-up (median, 69 months; range, 24-90 months). We also compared the ultrasound findings among the patients to a control group of 100 blood donors without musculoskeletal pain. Clinical arthritis developed in 39/82 patients (48%) after a median of 6 months (range, 1-71 months). One or more ultrasound erosions occurred in 13/82 patients (16%), with none in control subjects (p < 0.001). Clinical arthritis development was more common among patients with baseline ultrasound erosions than those without (77 vs. 42%, p = 0.032), and remained significant in a multivariable Cox regression analysis that included previously described prognostic factors (HR 3.9, 95% CI 1.6-9.4, p = 0.003). Ultrasound-detected tenosynovitis was more frequent among the patients and associated with clinical arthritis development in a univariable analysis (HR 2.5, 95% CI 1.1-5.7, p = 0.031), but did not remain statistically significant in multivariable analysis. Thus, bone erosions detected by ultrasound are independent predictors of clinical arthritis development in an ACPA-positive at-risk population. Trial Registration: Regional Ethics Committee in Linköping, Sweden, Dnr M220-09. Registered 16 December 2009, https://etikprovningsmyndigheten.se/.

Designed surface with tunable IgG density as an in vitro model for immune complex mediated stimulation of leukocytes.

We present the design of an in vitro model for immune-complex-mediated stimulation of leukocytes and its functional characteristics with respect to monocyte adhesion. The model was based on the orientation-controlled immobilization of a humanized IgG1 monoclonal antibody (rituximab) via its interaction with a biotinylated peptide epitope derived from the CD20 marker. The peptide was linked to neutravidin covalently attached to a mixed self-assembled monolayer of carboxyl- and methoxy-terminated oligo(ethylene glycol) alkane thiolates on gold. The surface adhesion propensity of human monocytes (cell line U937) was highly dependent on the lateral IgG density and indicated that there exists a distance between IgG-Fc on the surface where interactions with Fc gamma receptors are optimal. This well-defined platform allows for a careful control of the size and orientation of artificial IgG immune complexes, it is easily made compatible with, for example, cellular imaging, and it will become useful for in vitro studies on the importance of Fc gamma receptor interactions in chronic immune-mediated diseases.

Orofacial pain in juvenile idiopathic arthritis is associated with stress as well as psychosocial and functional limitations.

BACKGROUND: The aim of this study was to investigate relations between psychosocial factors, signs and symptoms of orofacial pain and jaw dysfunction in patients with juvenile idiopathic arthritis (JIA). METHODS: Forty-five patients with JIA (median age 12 years) and 16 healthy matched controls (median age 13 years) were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered the DC/TMD questionnaires regarding psychosocial factors (pain intensity, pain-related disability, depression, stress, catastrophizing, pain locations and jaw function). RESULTS: JIA patients with orofacial pain had higher degree of stress, depression, catastrophizing and jaw dysfunction compared to subjects without. In turn, these factors were associated with orofacial pain intensity. Also, patients with orofacial pain had higher systemic inflammatory activity. CONCLUSIONS: Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction and loss of daily living activities. Pain intensity seems to be the major pain aspect related to these factors. In addition, systemic inflammatory activity appears to be an important factor contributing to orofacial pain in JIA.

Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies.

OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. METHODS: Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. RESULTS: Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. CONCLUSION: These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort.

OBJECTIVE: In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. METHODS: We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. RESULTS: Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). CONCLUSION: The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

A simple method for heuristic modeling of expert knowledge in chronic disease: identification of prognostic subgroups in rheumatology.

Identification of prognostic subgroups is of key clinical interest at the early stages of chronic disease. The aim of this study is to examine whether representation of physicians' expert knowledge in a simple heuristic model can improve data mining methods in prognostic assessments of patients with rheumatoid arthritis (RA). Five rheumatology consultants' experiences of clinical data patterns among RA patients, as distinguished from healthy reference populations, were formally represented in a simple heuristic model. The model was used in K-mean-clustering to determine prognostic subgroups. Cross-sectional validation using physician's global assessment scores indicated that the simple heuristic model performed better than crude data made in identification of prognostic subgroups of RA patients. A simple heuristic model of experts' knowledge was found useful for semi-automatic data mining in the chronic disease setting. Further studies using categorical baseline data and prospective outcome variables are warranted and will be examined in the Swedish TIRA-program.

Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE.

OBJECTIVE: The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE. METHODS: Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual. RESULTS: Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of <12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p<0.0001), especially in the renal (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels. CONCLUSIONS: In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.

Decrease in bone mineral density during three months after diagnosis of early rheumatoid arthritis measured by digital X-ray radiogrammetry predicts radiographic joint damage after one year.

BACKGROUND: Periarticular osteopenia is an early sign of incipient joint injury in rheumatoid arthritis (RA), but cannot be accurately quantified using conventional radiography. Digital X-ray radiogrammetry (DXR) is a computerized technique to estimate bone mineral density (BMD) from hand radiographs. The aim of this study was to evaluate whether decrease in BMD of the hands (BMD loss), as determined by DXR 3 months after diagnosis, predicts radiographic joint damage after 1 and 2 years in patients with early RA. METHODS: Patients (n = 176) with early RA (<12 months after onset of symptoms) from three different Swedish rheumatology centers were consecutively included in the study, and 167 of these patients were included in the analysis. Medication was given in accordance with Swedish guidelines, and the patients were followed for 2 years. Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP) were measured at baseline, and 28-joint Disease Activity Score (DAS28) was assessed at each visit. Radiographs of the hands and feet were obtained at baseline, 3 months (hands only) and 1 and 2 years. Baseline and 1-year and 2-year radiographs were evaluated by the Larsen score. Radiographic progression was defined as a difference in Larsen score above the smallest detectable change. DXR-BMD was measured at baseline and after 3 months. BMD loss was defined as moderate when the decrease in BMD was between 0.25 and 2.5 mg/cm2/month and as severe when the decrease was greater than 2.5 mg/cm2/month. Multivariate regression was applied to test the association between DXR-BMD loss and radiographic damage, including adjustments for possible confounders. RESULTS: DXR-BMD loss during the initial 3 months occurred in 59% of the patients (44% moderate, 15% severe): 32 patients (19%) had radiographic progression at 1 year and 45 (35%) at 2 years. In multiple regression analyses, the magnitude of DXR-BMD loss was significantly associated with increase in Larsen score between baseline and 1 year (p = 0.033, adjusted R-squared = 0.069). CONCLUSION: DXR-BMD loss during the initial 3 months independently predicted radiographic joint damage at 1 year in patients with early RA. Thus, DXR-BMD may be a useful tool to detect ongoing joint damage and thereby to improve individualization of therapy in early RA.

Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage.

Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.

Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking.

BACKGROUND: A possible association between mucosal immunization and inflammation, as well as the initiation and propagation of rheumatoid arthritis (RA), is attracting renewed interest. The aim of this study was to evaluate the possible occurrence and clinical correlations of circulating secretory immunoglobulin A (SIgA) antibodies against the second-generation cyclic citrullinated peptides (CCP) among patients with recent-onset RA followed prospectively over 3 years. METHODS: Baseline serum samples from 636 patients with recent-onset RA were analyzed for SIgA anti-CCP antibodies by using an enzyme-linked immunosorbent assay with a secondary antibody directed against secretory component. SIgA anti-CCP status at baseline was analyzed in relation to smoking, HLA-DRB1/shared epitope (SE), and the disease course over 3 years. Significant findings were evaluated in regression analysis that included age, sex, smoking, and SE. RESULTS: Seventeen percent of the patients tested positive for circulating SIgA anti-CCP, and the occurrence was confirmed by detection of secretory component in an affinity-purified IgA anti-CCP fraction. SIgA anti-CCP positivity at baseline was associated with slightly higher baseline erythrocyte sedimentation rate (ESR) (mean 38 vs. 31 mm/first hour, p = 0.004) and C-reactive protein (CRP) (mean 30 vs. 23 mg/L, p = 0.047). During follow-up, SIgA anti-CCP-positive patients had a higher mean AUC regarding ESR (adjusted p = 0.003), although there were no significant differences regarding CRP, tender and swollen joint counts, or radiological joint damage (median Larsen progression 1.0 vs. 1.0, p = 0.22). SIgA anti-CCP was associated significantly with smoking (79 % ever smokers among SIgA anti-CCP-positive patients vs. 59 % in SIgA anti-CCP-negative patients, adjusted OR 2.19, 95 % CI 1.01-4.37, p = 0.027) but not with carriage of the SE (80 % vs. 73 %, p = 0.62). CONCLUSIONS: Circulating SIgA anti-CCP, which is present in a subgroup of patients with early RA, is not related to SE, but it is environmentally linked to cigarette smoking. This finding strengthens the hypothesis that immunization against citrullinated peptides and/or proteins may occur at mucosal surfaces of the airways. Analysis of SIgA antibodies in serum may be a convenient and more versatile means to investigate the "mucosal connection" in RA compared with analyses in mucosal fluid samples.

Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.

BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data. METHODS: Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available. RESULTS: There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients. CONCLUSIONS: In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis.

Dynamic Response Genes in CD4+ T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

Recent-onset rheumatoid arthritis: a 1-year observational study of correlations between health-related quality of life and clinical/laboratory data.

OBJECTIVE: To analyse correlations within and between clinical/laboratory assessments and health-related quality of life variables for recent-onset rheumatoid arthritis at the time of diagnosis and 12 months later. METHODS: A total of 297 patients with recent-onset (< or =12 months) rheumatoid arthritis were included at diagnosis and followed up for 12 months. Clinical/laboratory assessment was performed by erythrocyte sedimentation rate, C-reactive protein, 28-joint count of tender/swollen joints, physician's global assessment, grip force, grip ability, functional impairment and walking speed. The self-reported health-related quality of life included symptoms (pain, morning stiffness), patients estimated general health, Health Assessment Questionnaire and SF-36. RESULTS: All tested variables improved within 6 months of diagnosis and then remained stable but still affected at the 12-month follow-up. Multivariate correlations between clinical/laboratory variables and health-related quality of life were weak. At inclusion, clinical/laboratory assessments explained 18% of health-related quality of life at the same time-point and predicted 7% of the variation in health-related quality of life after 12 months. CONCLUSION: The time-course followed similar patterns for most variables, but only a small part of the variation in health-related quality of life was explained or predicted by the clinical/laboratory variables. This implies that health-related quality of life adds important information to clinical/laboratory assessments in clinical practice and should be considered in goal setting together with clinical/laboratory assessment in order to optimize healthcare and outcome.

Application of the 2012 Systemic Lupus International Collaborating Clinics classification criteria to patients in a regional Swedish systemic lupus erythematosus register.

INTRODUCTION: In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) network presented a new set of criteria (SLICC-12) to classify systemic lupus erythematosus (SLE). The present study is the first to evaluate the performance of SLICC-12 in an adult European study population. Thus, SLICC-12 criteria were applied to confirmed SLE cases in our regional SLE register as well as to individuals with a fair suspicion of systemic autoimmune disease who were referred to rheumatology specialists at our unit. METHODS: We included 243 confirmed SLE patients who met the 1982 American College of Rheumatology (ACR-82) classification criteria and/or the Fries 'diagnostic principle' (presence of antinuclear antibodies on at least one occasion plus involvement of at least two defined organ systems) and 55 controls with possible systemic autoimmune disease, including the presence of any SLE-related autoantibody. RESULTS: SLICC-12 showed a diagnostic sensitivity of 94% (95% confidence interval (CI), 0.90 to 0.96) compared with 90% (95% CI, 0.85 to 0.93) for the updated set of ACR criteria from 1997 (ACR-97), whereas ACR-82 failed to identify every fifth true SLE case. However, the disease specificity of SLICC-12 reached only 74% (95% CI, 0.60 to 0.84) and did not change much when involvement of at least two different organs was required as an indicator of systemic disease. In addition, SLICC-12 misclassified more of the controls compared to ACR-82, ACR-97 and Fries. CONCLUSIONS: Establishing a standard definition of SLE continues to challenge lupus researchers and clinicians. We confirm that SLICC-12 has advantages with regard to diagnostic sensitivity, whereas we found the diagnostic specificity to be surprisingly low. To accomplish increased sensitivity and specificity figures, a combination of criteria sets for clinical SLE studies should be considered.