Treat-to-target strategies for the management of familial Mediterranean Fever in children.

BACKGROUND: The objective of this initiative was to develop a treat-to-target (T2T) approach for the management of patients with Familial Mediterranean Fever (FMF), including the definition of a complex treatment target, and establish strategies that improve patient care and long-term outcome. METHODS: An initial set of statements as well as a flow chart visualising the proposed concept was developed. To adapt the preliminary statements to the current state of knowledge, a systematic literature search was performed and the modified statements were subject to a Delphi approach. To ensure the applicability of the statements in daily practice, an online survey was conducted among paediatric rheumatologists in Germany. In addition, data from the national AID-NET registry were analysed with respect to therapeutic response. RESULTS: This T2T initiative yielded a total of 26 statements guiding FMF management with respect to diagnosis, treatment targets, treatment strategies and monitoring. The online survey identified cut-off values for inflammatory markers indicating treatment intensification and appropriate measures in case of colchicine intolerance or non-adherence. The analysis of data derived from the national AID-NET showed that colchicine therapy was successfully terminated in 61% of patients (27 out of 44) with heterozygous MEFV mutations. Multidimensional treatment targets incorporating objective and subjective reported outcome measures were developed. These provide the basis for stratifying patients into the following treatment paths: continue colchicine, persisting attacks / inflammation, colchicine intolerance, persisting arthritis, colchicine reduction and adjustment/reduction of biologics. CONCLUSIONS: The proposed consensus treatment plan for the management of FMF incorporates multidimensional targets allowing transparent treatment decisions, which will promote personalised disease management and increase adherence to therapy.

Early diagnosis and response assessment in chronic recurrent multifocal osteomyelitis: changes in lesion volume and signal intensity assessed by whole-body MRI.

OBJECTIVE: To assess the effectiveness of whole-body MRI (WB-MRI) in early diagnosis of chronic recurrent multifocal osteomyelitis (CRMO) and the prediction of clinical response through quantitative MRI features. METHODS: 20 children (mean age, 10.3 years; range, 5-14 years) with CRMO underwent WB-MRI and were assessed with a clinical score (Jansson) at baseline (median time after first encounter, 8 months) and follow-up (median time after baseline, 11.5 months). Baseline WB-MRI scans were classified as early (within 6 months after first encounter) and late. Clinical responders and non-responders were compared regarding number and localization of bone lesions, lesion volume and T2 signal intensity (SI) ratio (lesion to muscle). RESULTS: Diagnosis of CRMO was made promptly in the early WB-MRI group (n = 10; median, 3 months) compared to the late WB-MRI group (n = 10; 18 months; p = 0.006). Bone lesions were mainly located in the lower extremities (n = 119/223; 53%). No significant difference was detected regarding the number of bone lesions and lesion volume in the subgroups of clinical responders (n = 10) and non-responders (n = 10). Responders showed a higher volume reduction of bone lesions at follow-up compared to non-responders (p = 0.03). Baseline and follow-up SI ratios were lower in responders (5.6 and 5.8 vs 6.1 and 7.2; p = 0.047 and p = 0.005). CONCLUSION: The use of WB-MRI within 6 months of disease suspicion may serve as a benchmark to support early diagnosis of CRMO. T2 SI ratios and the reduction of lesions' volume correlate with clinical outcome. ADVANCES IN KNOWLEDGE: WB-MRI at an early stage of suspected CRMO plays a key role for early diagnosis. This is the first study showing that quantitative MRI features are suitable for response assessment and can be used as prognostic markers for the prediction of clinical response.

BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome activity.

Activity of the NLRP3 inflammasome, a critical mediator of inflammation, is controlled by accessory proteins, posttranslational modifications, cellular localization, and oligomerization. How these factors relate is unclear. We show that a well-established drug target, Bruton's tyrosine kinase (BTK), affects several levels of NLRP3 regulation. BTK directly interacts with NLRP3 in immune cells and phosphorylates four conserved tyrosine residues upon inflammasome activation, in vitro and in vivo. Furthermore, BTK promotes NLRP3 relocalization, oligomerization, ASC polymerization, and full inflammasome assembly, probably by charge neutralization, upon modification of a polybasic linker known to direct NLRP3 Golgi association and inflammasome nucleation. As NLRP3 tyrosine modification by BTK also positively regulates IL-1ß release, we propose BTK as a multifunctional positive regulator of NLRP3 regulation and BTK phosphorylation of NLRP3 as a novel and therapeutically tractable step in the control of inflammation.

State of care for patients with systemic autoinflammatory diseases - Results of a tertiary care survey.

BACKGROUND: Systemic autoinflammatory diseases (SAIDs) are rare debilitating disorders of which there is limited awareness and a significant delay in diagnosis. There is no uniform approach in the diagnosis and treatment of these disorders and the real life state of SAID patient care is poorly characterized. The aim of this study was to obtain data on the epidemiology, state of care and the perception of physicians who are involved in the care of SAID patients. METHODS: We performed a questionnaire-based survey and contacted 134 university departments of dermatology, pediatrics, rheumatology and other SAID departments of tertiary care in German-speaking countries. RESULTS: A total of 37 departments participated in the survey. The majority of departments managed both adult and pediatric patients with a variety of monogenic and polygenic/acquired SAIDs. For monogenic SAIDs such as cryopyrin-associated periodic syndromes (CAPS) and familial Mediterranean fever (FMF), the diagnostic and treatment strategies were similar among the departments. The diagnostic work-up included inflammatory markers and genetic testing, the first line treatment interleukin-1 (IL-1) blockers for CAPS and colchicine for FMF. For polygenic/acquired SAIDs, we observed a significant heterogeneity in diagnostic and therapeutic approaches. As a major unmet need, diagnostic delay was identified with a median time to diagnosis of 2 (range 1-5) years. The overall state of care for SAID patients was rated to be excellent or good by only 12% of departments, and to be poor or non-sufficient by 40% of departments. CONCLUSION: This study demonstrates a high need to improve the state of care and to harmonize diagnostic and treatment strategies for SAID patients.

[Autoinflammatory Diseases as a Differential Diagnosis of Fever of Unknown Origin]. / Autoinflammatorische Erkrankungen als Differenzialdiagnose des Fiebers unklarer Genese.

Fever is the most leading symptom of autoinflammatory diseases (AID). Therefore, AID have to be considered in differential diagnosis concerning fever of unknown origin. Unspecific Inflammatory manifestations may lead to misinterpretations that possibly cause irreversible organ damage. Effective treatment options are available and imply profound diagnostics.

Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase.

BACKGROUND: The Nod-like receptor NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK) are protagonists in innate and adaptive immunity, respectively. NLRP3 senses exogenous and endogenous insults, leading to inflammasome activation, which occurs spontaneously in patients with Muckle-Wells syndrome; BTK mutations cause the genetic immunodeficiency X-linked agammaglobulinemia (XLA). However, to date, few proteins that regulate NLRP3 inflammasome activity in human primary immune cells have been identified, and clinically promising pharmacologic targeting strategies remain elusive. OBJECTIVE: We sought to identify novel regulators of the NLRP3 inflammasome in human cells with a view to exploring interference with inflammasome activity at the level of such regulators. METHODS: After proteome-wide phosphoproteomics, the identified novel regulator BTK was studied in human and murine cells by using pharmacologic and genetic BTK ablation. RESULTS: Here we show that BTK is a critical regulator of NLRP3 inflammasome activation: pharmacologic (using the US Food and Drug Administration-approved inhibitor ibrutinib) and genetic (in patients with XLA and Btk knockout mice) BTK ablation in primary immune cells led to reduced IL-1ß processing and secretion in response to nigericin and the Staphylococcus aureus toxin leukocidin AB (LukAB). BTK affected apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and caspase-1 cleavage and interacted with NLRP3 and ASC. S aureus infection control in vivo and IL-1ß release from cells of patients with Muckle-Wells syndrome were impaired by ibrutinib. Notably, IL-1ß processing and release from immune cells isolated from patients with cancer receiving ibrutinib therapy were reduced. CONCLUSION: Our data suggest that XLA might result in part from genetic inflammasome deficiency and that NLRP3 inflammasome-linked inflammation could potentially be targeted pharmacologically through BTK.

Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study.

OBJECTIVES: Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients. METHODS: A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO). RESULTS: Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056). CONCLUSIONS: The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials.

Efficacy and safety of etanercept in patients with the enthesitis-related arthritis category of juvenile idiopathic arthritis: results from a phase III randomized, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of etanercept in patients with enthesitis-related arthritis (ERA) in juvenile idiopathic arthritis (JIA). METHODS: This was a 2-phase study in JIA patients with active, refractory ERA. Phase I was an open-label, uncontrolled 24-week study period in which all patients were administered etanercept. Patients considered to be treatment responders at week 24 according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement in juvenile arthritis entered the second phase, a 24-week randomized, double-blind, placebo-controlled withdrawal study, for an additional 24 weeks, for evaluation of the primary end point, occurrence of a disease flare from week 24 to week 48, based on the ACR preliminary definition of disease flare in juvenile arthritis. RESULTS: Forty-one patients were enrolled. At week 24, treatment with etanercept resulted in response rates of 93%, 93%, 80%, 56%, and 54% based on the ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria, respectively. In addition, a marked decrease in all disease activity measures was observed. The mean number of tender joints, swollen joints, and joints with active arthritis decreased by 91%, 97%, and 94%, respectively. Physician's global assessment of disease activity, parent's assessment of patient's overall well-being, and the Childhood Health Assessment Questionnaire disability index improved by 91%, 80%, and 86%, respectively. The number of tender enthesis sites and total scores for back pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Juvenile Arthritis Disease Activity Score based on 10-joint counts (JADAS10) decreased by 75%, 72%, 81%, 72%, 85%, and 87%, respectively. In phase II, 38 patients were randomly assigned to receive placebo (n = 18) or to continue receiving etanercept (n = 20). Up to week 48, 12 disease flares occurred, in 9 patients receiving placebo and 3 patients receiving etanercept (odds ratio 6.0, P = 0.02). There were no serious infections, malignancies, or deaths. CONCLUSION: In this study of patients with the ERA category of JIA, etanercept proved effective, as indicated by high ACR Pedi response rates and JADAS10 response rates at week 24. Patients who continued treatment with etanercept had significantly fewer flares than those who received placebo, although 50% of patients in the placebo group did not experience a flare. Treatment suspension may be a consideration for patients with the ERA category of JIA who achieve remission.

Localization and functionality of the inflammasome in neutrophils.

Neutrophils represent the major fraction of circulating immune cells and are rapidly recruited to sites of infection and inflammation. The inflammasome is a multiprotein complex that regulates the generation of IL-1 family proteins. The precise subcellular localization and functionality of the inflammasome in human neutrophils are poorly defined. Here we demonstrate that highly purified human neutrophils express key components of the NOD-like receptor family, pyrin domain containing 3 (NLRP3), and absent in melanoma 2 (AIM2) inflammasomes, particularly apoptosis-associated speck-like protein containing a CARD (ASC), AIM2, and caspase-1. Subcellular fractionation and microscopic analyses further showed that inflammasome components were localized in the cytoplasm and also noncanonically in secretory vesicle and tertiary granule compartments. Whereas IL-1ß and IL-18 were expressed at the mRNA level and released as protein, highly purified neutrophils neither expressed nor released IL-1α at baseline or upon stimulation. Upon inflammasome activation, highly purified neutrophils released substantially lower levels of IL-1ß protein compared with partially purified neutrophils. Serine proteases and caspases were differentially involved in IL-1ß release, depending on the stimulus. Spontaneous activation of the NLRP3 inflammasome in neutrophils in vivo affected IL-1ß, but not IL-18 release. In summary, these studies show that human neutrophils express key components of the inflammasome machinery in distinct intracellular compartments and release IL-1ß and IL-18, but not IL-1α or IL-33 protein. Targeting the neutrophil inflammasome may represent a future therapeutic strategy to modulate neutrophilic inflammatory diseases, such as cystic fibrosis, rheumatoid arthritis, or sepsis.

A Retrospective Patient Chart Review and Survey in Patients with Cryopyrin-associated Periodic Syndromes Treated with Anakinra.

Background: Cryopyrin-associated periodic syndromes (CAPS) is a group of rare autoinflammatory diseases. Little is known about the burden of disease, patients' views on treatment, and adverse events (AEs) with current therapy. Objectives: The main study objective was to quantify the patients' burden of disease in terms of flares and resource use and to characterize patient symptomatology and tolerability of treatment with anakinra. A secondary objective included comparing chart review and patient recall of symptoms and AEs. Methods: A retrospective medical chart review and concurrent online patient survey was conducted in four European countries. Data 12 months prior to initiation of/during anakinra treatment were entered into web-based case report forms by study groups. Results: Forty-two patients received/were receiving anakinra as primary treatment for at least 12 months. Patients experienced a 79.5% reduction in flares after commencing anakinra treatment. During the past 12 months on anakinra, four of five (80%) patients who recalled experiencing flares reported cancelling social activities and staying home as the most common courses of action. Most common AEs were injection site pain upon treatment initiation and weight gain. According to patient recall, 12 of 21 patients (57.1%) discontinued anakinra to enter another clinical trial; of the 12, eight (38%) specifically discontinued anakinra only for that reason, and four patients cited entering a clinical trial as one of many reasons for discontinuing anakinra. Conclusions: To our knowledge, this is the most comprehensive survey of patient experience with CAPS. Although improved, CAPS treatment remains suboptimal and a significant burden is placed upon patients, caregivers, and the healthcare system. With new agents available, it will be important to compare outcomes in patients using all therapeutic options.

An international registry on autoinflammatory diseases: the Eurofever experience.

OBJECTIVE: To report on the demographic data from the first 18 months of enrollment to an international registry on autoinflammatory diseases in the context of the Eurofever project. METHODS: A web-based registry collecting baseline and clinical information on autoinflammatory diseases and related conditions is available in the member area of the PRINTO web-site. Anonymised data were collected with standardised forms. RESULTS: 1880 (M:F=916:964) individuals from 67 centers in 31 countries have been entered in the Eurofever registry. Most of the patients (1388; 74%), reside in western Europe, 294 (16%) in the eastern and southern Mediterranean region (Turkey, Israel, North Africa), 106 (6%) in eastern Europe, 54 in Asia, 27 in South America and 11 in Australia. In total 1049 patients with a clinical diagnosis of a monogenic autoinflammatory diseases have been enrolled; genetic analysis was performed in 993 patients (95%): 703 patients have genetically confirmed disease and 197 patients are heterozygous carriers of mutations in genes that are mutated in patients with recessively inherited autoinflammatory diseases. The median diagnosis delay was 7.3 years (range 0.3-76), with a clear reduction in patients born after the identification of the first gene associated with autoinflammatory diseases in 1997. CONCLUSIONS: A shared online registry for patients with autoinflammatory diseases is available and enrollment is ongoing. Currently, there are data available for analysis on clinical presentation, disease course, and response to treatment, and to perform large scale comparative studies between different conditions.

Localized scleroderma: MR findings and clinical features.

PURPOSE: To describe musculoskeletal manifestations seen at magnetic resonance (MR) imaging in patients with localized scleroderma (LS) and to examine the relationship of MR findings to clinical subtypes and clinically suspected musculoskeletal features. MATERIALS AND METHODS: Institutional review board approval was obtained. Forty-three patients (30 female, 13 male; mean age, 42 years) with LS underwent MR imaging with a 1.5-T MR imager between November 2005 and June 2010. Findings were classified into clinical subtypes according to recently published consensus criteria. Images were evaluated for morphologic changes and signal abnormalities of subcutaneous fat septa, muscle fasciae, intramuscular septa, joint and/or tendon sheath synovia, entheses, and bone marrow. Clinically suspicious features of musculoskeletal manifestations-such as articular or periarticular pain, joint contractures, swelling, and increased warmth of the joints or extremities-were recorded. RESULTS: Musculoskeletal involvement was detected with MR imaging in 32 (74%) of 43 patients. It was detected with MR imaging in 26 (96%) of 27 patients in whom it was clinically suspected and in six (38%) of 16 patients in whom it was not clinically suspected. We found fascial thickening (26 [60%] of 43 patients), increased fascial enhancement (23 [53%] of 43 patients), articular synovitis (17 [40%] of 43 patients), tenosynovitis (nine [21%] of 43 patients), perifascial enhancement (seven [16%] of 43 patients), myositis (six [14%] of 43 patients), enthesitis (three [7%] of 43 patients), bone marrow involvement (two [5%] of 43 patients), and subcutaneous septal thickening (28 [65%] of 43 patients). The highest prevalence of musculoskeletal involvement was seen in patients with pansclerotic morphea. CONCLUSION: MR imaging reveals musculoskeletal involvement in patients with localized scleroderma.

MRI findings in psoriatic arthritis of the hands.

OBJECTIVE: The purpose of this essay is to provide a practical review of the spectrum of morphologic and functional MRI findings in psoriatic arthritis of the hand joints. CONCLUSION: The MRI findings of psoriatic arthritis include enthesitis, bone marrow edema, and periostitis accompanying articular or flexor tendon sheath synovitis in the early stage accompanied by destructive and proliferative bony changes, subluxation, and ankylosis in the late stage.

Risk factors for severe Muckle-Wells syndrome.

OBJECTIVE: Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease resulting in excessive interleukin-1 release. It is unknown whether demographic, clinical, or laboratory characteristics at the time of diagnosis may identify patients who are at high risk for severe disease activity. This study was undertaken to analyze clinical and laboratory features of MWS, compare genetically defined subcohorts, and identify risk factors for severe MWS. METHODS: A multicenter cohort study of consecutive MWS patients was performed. Parameters assessed included clinical features, MWS Disease Activity Score (MWS-DAS), inflammation markers, and cytokine levels. E311K mutation-positive patients were compared with E311K mutation-negative patients. Putative risk factors for severe MWS (defined as an MWS-DAS score of ≥10) were assessed in univariate analyses, and significant predictors were entered into a multivariate model. RESULTS: Thirty-two patients (15 male and 17 female) were studied. The most frequent organ manifestations were musculoskeletal symptoms and eye and skin disorders. Renal disease and hearing loss were seen in >50% of the patients. Genetically defined subcohorts had distinct phenotypes. Severe disease activity was documented in 19 patients (59%). Predictors of severe MWS identified at the time of diagnosis were female sex, hearing loss, musculoskeletal disease, increased erythrocyte sedimentation rate, and low hemoglobin level. Female sex and hearing loss remained significant after adjustment for age in a multivariate model (relative risk 1.8 and 2.6, respectively). CONCLUSION: MWS patients at high risk for severe disease can be identified at the time of diagnosis. Female patients presenting with hearing loss have the highest likelihood of manifesting severe MWS and should be considered a high-risk group.

Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis.

OBJECTIVES: Etanercept, a recombinant TNF receptor fusion protein, has been approved for the treatment of resistant polyarticular course juvenile idiopathic arthritis at a dosage of 0.4 mg/kg twice weekly in children older than 4 years. In adult patients, efficacy and safety of etanercept 25 mg twice weekly was comparable with 50 mg once weekly. Therefore, safety and efficacy of etanercept once weekly 0.8 mg/kg up to 50 mg s.c. was evaluated in a 3 month open label trial. METHODS: Twenty patients 4 to 17 years old received 0.8 mg of etanercept per kilogram of body weight subcutaneously once weekly for 3 months in an open multicentre trial. Active polyarticular disease was defined by the presence of five or more active joints with swelling, alternatively with pain or tenderness combined with limitation of motion. Safety assessments were based on adverse events (AEs) reports. Efficacy was assessed using the PedACR30/50/70 criteria. RESULTS: At the start of treatment the patients showed high disease activity. A rapid reduction of all disease activity parameters was observed. A PedACR30/50/70 response was reached by 75%/35%/10% of patients after 4 weeks, 90%/75%/35% after 8 weeks and 95%/75%/75% after 12 weeks of treatment. There were 37 AEs, none of them serious, with injection site reactions and minor infections being the most frequent. There was no drop out. Long-term follow-up of the patients will be carried out in the German JIA Registry. CONCLUSION: Treatment with etanercept once weekly using a double dosage leads to a significant improvement of disease activity in patients with active polyarticular course juvenile idiopathic arthritis and is well tolerated.

Tumor necrosis factor-alpha blocker in treatment of juvenile idiopathic arthritis-associated uveitis refractory to second-line agents: results of a multinational survey.

OBJECTIVE: Uveitis occurs in 10%-15% of patients with juvenile idiopathic arthritis (JIA). If topical treatment fails, second-line agents are used to control the disease. However, some patients need the addition of tumor necrosis factor-alpha (TNF-alpha) antagonist (anti-TNF). We organized a cross-sectional cohort to investigate use and efficacy of anti-TNF treatment in patients with JIA-associated uveitis. METHODS: The international pediatric rheumatology community was queried about the use and efficacy of anti-TNF in treatment of JIA-associated uveitis using an E-mail survey. RESULTS: Of the 33 responding centers following 884 patients with uveitis, only 15 centers, following 404 patients, were using anti-TNF for this indication. A total of 47 patients with JIA-related uveitis treated with anti-TNF because of an insufficient response to previous therapy were reported. The mean age of the patients was 12.5 years. The mean duration from onset of uveitis to start of anti-TNF treatment was 45.1 months. Three different anti-TNF agents were used: etanercept in 34 cases, infliximab in 25 cases, and adalimumab in 3 cases. In 12 of the 34 patients etanercept was inefficacious and patients were switched to infliximab. The final response was rated according to a composite index as 53%/12%/32%, and according to physician rating as 47%/12%/38% representing good, moderate, and poor, respectively, in the etanercept group; and 70%/30%/0% and 68%/24%/0% in the infliximab group. All 3 patients taking adalimumab were responders. Infliximab was statistically significantly more efficacious for the treatment of JIA-associated uveitis than etanercept (chi-square p = 0.004). CONCLUSION: Anti-TNF seems to be an effective treatment for refractory JIA-associated uveitis. In this cohort infliximab was more efficacious than etanercept.

Autoantibodies in juvenile idiopathic arthritis: glucose-6-phosphate isomerase is not a specific target.

OBJECTIVE: Antibodies recognizing the ubiquitous cytosolic enzyme glucose-6-phosphate isomerase (GPI) cause arthritis in the K/BxN mouse model. Studies have shown that these antibodies are not specific for rheumatoid arthritis (RA) in humans. We evaluated GPI as a target of autoantibodies in juvenile idiopathic arthritis (JIA). METHODS: We studied 324 serum and 48 synovial fluid (SF) samples from 103 patients with JIA, 36 with RA, and 8 with arthralgia and 11 controls. Anti-GPI antibodies were assessed by densitometrically evaluating immunoblots and ELISA using native and recombinant GPI. We determined the GPI activity of the soluble antigen in serum and SF. RESULTS: Although several samples contained anti-GPI-IgG antibodies, this was not specific for JIA or its subgroups, or for RA. Other proteins in the GPI preparation were also frequently recognized by antibodies. Additionally, we observed increased GPI activity in patients with the systemic manifestation of JIA, but not in other patients. Neither anti-GPI concentrations nor GPI activity were associated with disease activity. CONCLUSION: In addition to the findings in RA, our results indicate that GPI is not a general target of autoantibodies in JIA.