Background JIA is the most common chronic inflammatory rheumatic diseases of childhood. Due to their long-term safety and efficacy, biologic disease modifying antirheumatic drugs (DMARD) are commonly necessary for control of pJIA patients (pts). Objectives To evaluate 6-year (y) safety and 2 y effectiveness profile of Adalimumab with or without methotrexate (ADA±MTX) when used in current clinical practice for the treatment of moderately to severely active pJIA. Methods This is a 6 y interim analysis of an ongoing, multicenter, non-interventional, observational registry of pts with moderately to severely active pJIA with up to10 y safety follow-up. Included pts are treated with either ADA±MTX or MTX alone as part of their routine clinical care enrolled in the US, EU, and Australia. MedDRA observational adverse events (AEs) were recorded from the first day in the registry through last contact, irrespective of the duration of registry treatment. Effectiveness was assessed by 27-joint juvenile arthritis disease activity score (JADAS27), based on CRP. Results As of January 2014, enrollment was complete. As of June 1, 2015 cut-off date, 846 pts (543 in ADA±MTX and 303 in MTX groups) were treated in the registry. There were 39 pts who rolled over from the MTX to the ADA±MTX arm. At registry entry mean pJIA disease duration was 1.4 y and 3.7 y for MTX and ADA±MTX arms, respectively. At baseline (BL), mean AJC71 was 5.8 and 5.3 for MTX and ADA±MTX arms, respectively, and Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) was 0.6 for both arms. At data cutoff, the mean duration of study exposure was 1.81 y and 2.15 y for MTX and ADA±MTX arms, respectively. Overall, 206 pts (68%) in the MTX and 216 pts (39.8%) in the ADA±MTX arms discontinued registry drug through 6 y. The main reasons for registry drug discontinuation for the MTX arm: pts required additional therapy (32.3%), other (11.9%), lack of efficacy (10.9%), AEs (8.3%), or pts achieved JIA remission (7.6%), and for ADA±MTX arm: lack of efficacy (16%), lost to follow-up (7.2%), other (5.9%), and AEs (5.3%). Frequencies and rates of treatment-emergent AEs were similar to those reported for observational AEs (Table). There were no reports of deaths, malignancies, opportunistic infections, active TB, oral candidiasis, or CHF. Mean JADAS27 (CRP) improved from 12.2 at BL to 9.7, 5.2, 4.4, 3.5, 2.2 at months 1, 6, and 12, 18, 24 for pts in the MTX and from 11.8 at BL to 7.0, 4.-2, 4.2, 3.6, 3.9 in the ADA±MTX arms, respectively (observed data). Conclusions Overall, ADA±MTX was well-tolerated in these pts with pJIA with no new safety signals. Discontinuations from the registry drug were relatively high through 6 y, but greater in the MTX only arm. Acknowledgement AbbVie sponsored the study & contributed with PRINTO & PRCSG to the analysis, review, and approval of the abstract. Xiaolei Leahy & Ashish Deshmukh of AbbVie contributed to the research. Medical writing support was provided by Gaurav Patki, PhD, of AbbVie. Disclosure of Interest N. Ruperto Grant/research support from: AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfgroupaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, and Wyeth Phgroupaceuticals., Employee of: GASLINI Hospital, Speakers bureau: Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, Janssen Biologics B.V., MedImmune, Roche, and Wyeth/Pfizer, D. J. Lovell Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UBC, Xoma, and Genentech, Speakers bureau: Wyeth Pharmaceuticals, and served on data and safety monitoring boards for Amgen and Forest Research, C. Wallace Grant/research support from: Pfizer and Amgen, Consultant for: Amgen and Novartis., M. Toth: None declared, I. Foeldvari Consultant for: AbbVie and Novartis, J. Bohnsack Consultant for: Novartis, D. Milojevic Consultant for: Genentech and Novartis, E. Rabinovich Grant/research support from: UCB Pharma, Janssen Research & Development, LLC, Hoffmann-La Roche Inc., and AbbVie, D. Kingsbury Grant/research support from: AbbVie, K. Marzan Grant/research support from: AbbVie., P. Quartier Grant/research support from: AbbVie, Novartis, Consultant for: AbbVie, Novartis, K. Minden Grant/research support from: Pfizer and Abbvie, Consultant for: Pfizer, Abbvie, Roche/Chugai, Novartis, Medac and Pharma-Allergan., E. Chalom Speakers bureau: AbbVie, G. Horneff Grant/research support from: AbbVie, Pfizer, and Roche, Speakers bureau: AbbVie, Novartis, Pfizer, and Roche, R. M. Kuester Grant/research support from: AbbVie Inc. and Wyeth/Pfizer, J. Dare Grant/research support from: AbbVie, AstraZeneca, Bristol-Myers Squibb, Horizon Pharma, Medac, Pfizer, Roche, and UCB, M. Heinrich Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, H. Kupper Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, J. Kalabic Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, A. Martini Grant/research support from: AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, and Wyeth Pharmaceuticals, Employee of: GASLINI Hospital, Speakers bureau: Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, and MedImmune., H. I. Brunner Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Boehringer-Ingelheim, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UCB, and Genentech, Speakers bureau: Genentech Pharmaceuticals.

Background Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases of childhood. Adalimumab (ADA) is approved for use in moderate to severe polyarticular JIA (pJIA) patients (pts) ≥4 years (yrs) in the US, EU, Australia, and Japan, and was recently approved in EU for pts 2 to <4 yrs. Objectives To evaluate long-term safety and effectiveness of ADA in pts with moderately to severely active pJIA who are prescribed and treated with ADA in routine clinical practice. Methods This is an ongoing, multicenter, non-interventional, observational registry of pts diagnosed with moderately to severely active pJIA that are prescribed and treated in a routine clinical setting with either ADA ± ethotrexate (MTX) or MTX alone. Approximately 800 pts (500 in ADA arm/300 in MTX arm) will be enrolled in the US, EU, and Australia. The follow-up observational period is 10 yrs from enrollment into one of the treatment arms. For pts that switch from MTX monotherapy to ADA ± MTX, the 10 yr follow-up period will begin when they enroll into the ADA arm. Observational adverse events (AEs) were recorded from the first day in the registry through last contact, irrespective of treatment duration. Clinical outcomes were assessed by 71-joint juvenile arthritis disease activity score (JADAS71). Results As of June 2013, 765 pts (459 in ADA arm/306 in MTX arm) were enrolled and treated. The mean pJIA disease duration at baseline was 1.3 and 3.8 yrs for MTX and ADA arms, respectively. At baseline, there was a mean AJC of 5.8 and disability index of childhood health assessment questionnaire (DICHAQ) of 0.6 for both groups. Overall, 131 pts (42.8%) in the MTX arm and 81 pts (17.6%) in the ADA arm have discontinued registry drug. Of those, 23 (7.5%) and 25 (5.4%) pts in the MTX and ADA arm, respectively, discontinued due to an AE, and 34 out of the 131 pts in the MTX arm discontinued as they switched to the ADA arm. The observational AEs are summarized in the Table. No deaths, malignancies, or opportunistic infections were reported. 12 (2.6%) pts in the ADA arm had a serious infectious AE (including acute tonsillitis, cellulitis, gastroenteritis, mononucleosis, viral meningitis, pneumonia, pyelonephritis, scarlet fever, subcutaneous abscess, tonsillitis, urinary tract infection, and varicella). Frequencies and rates of treatment-emergent AEs were similar to those reported for observational AEs. Mean JADAS71 improved from 13.1 at baseline to 11.2, 6.4, 5.1 at months 1, 3 and 6 for pts in the MTX arm and from 12.1 at baseline to 8.5, 5.7, 5.4 in the ADA arm, respectively (observed data). Table 1. Overview of Observational Adverse Events (AEs) MTX (N=306) ADA (N=459) Any AE 125 (40.8) 142 (30.9) At least “possibly drug related” per the investigator 63 (20.6) 71 (15.5) Severe AE 12 (3.9) 22 (4.8) Serious AE 16 (5.2) 30 (6.5) AE leading to discontinuation of study drug 23 (7.5) 25 (5.4) Infectious AE 64 (20.9) 80 (17.4) Serious infectious AE 7 (2.3) 12 (2.6) Injection site-related AE 3 (1.0) 20 (4.4) Conclusions Overall, ADA is well-tolerated in these pts with active pJIA. No new safety signals were observed, and based on this analysis, the known safety profile of ADA remains unchanged. Acknowledgements AbbVie sponsored the study (NCT00783510), contributed to the design, and participated in collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final version. Medical writing support was provided by Jessica L. Suboticki, PhD, of AbbVie. Disclosure of Interest G. Horneff Grant/research support: AbbVie, Pfizer, and Roche, Speakers bureau: AbbVie, Novartis, Pfizer, and Roche, N. Ruperto Employee of: GASLINI Hospital, which has received contributions to support the research activities of the network of PRINTO from AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, and Wyeth Pharmaceuticals, Speakers bureau: Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, Janssen Biologics B.V., MedImmune, Roche, and Wyeth/Pfizer, C. Wallace Grant/research support: Pfizer and Amgen, Consultant for: Amgen and Novartis, M. Bereswill Shareholder of: AbbVie, Employee of: AbbVie, A. Cardoso Shareholder of: AbbVie, Employee of: AbbVie, J. Kalabic Shareholder of: AbbVie, Employee of: AbbVie, H. Kupper Shareholder of: AbbVie, Employee of: AbbVie, H. Brunner Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UCB, and Genentech, Speakers bureau: Genentech Pharmaceuticals DOI 10.1136/annrheumdis-2014-eular.1281

Background Juvenile Idiopathic Arthritis (JIA) patients have arthritis onset of unknown cause that lasts >6 weeks in the inflamed joints of children younger than 16 years. JIA is a complex genetic trait with established increased familial risk and robustly replicated genetic associations (e.g. HLA, PTPN2). Multiple single nucleotide polymorphisms (SNPs) in the 22q13.1 locus have reached genome-wide significance in recent genetic association studies using the Immunochip. The 22q13.1 locus contains both IL2RB and RAC2 which are attractive candidates to influence JIA pathology and have respective roles in IL-2 signaling and cell migration. Objectives To identify the statistically, bioinformatically and experimentally most plausible causal SNPs associated with risk of JIA in the 22q13 region. Methods We fine mapped the 22q13.1 locus using data from large scale genotyping projects of a European ancestry cohort of subjects with (3,905) and without JIA (14,388) to predict variants most likely causal at the 22q13.1 locus. Logistic regression conditional analysis was used to define regions of association followed by Bayesian analysis to define variants with large posterior probabilities. Transcription factor binding predictions were used to identify variants for experimental testing by electrophoretic mobility shift assay (EMSA). We limited our investigation to polyarticular RF- and oligoarticular JIA cases to reduce phenotypic heterogeneity. Results Conditional analyses showed independent associations to JIA in both the IL2RB and RAC2 loci. We identified two SNPs that can account for all of the JIA genetic association in this region. Using a Bayesian analysis we identified the SNPs that explained 95% of the posterior probability in the region and are the most likely to be causal. Altered nuclear extract binding was observed with risk and non-risk alleles in the IL2RB locus but not RAC2. These experimental data are consistent with the predicted alteration in transcription factor binding. Conclusions Polymorphic variants in the RAC2 and the nearby IL2RB locus are independent JIA risk loci. Use of the statistical and bioinformatics approach to produce candidates for laboratory validation is an important strategy in defining the function of risk variants in JIA. Disclosure of Interest None declared

Background Juvenile idiopathic arthritis (JIA) is the most common arthritic disease of childhood and is caused by a combination of genes and environment. In the last few years great advances have been made in dissecting the genetic basis of JIA with now 17 confirmed susceptibility loci identified. One of these loci, the MHC region, has been established for many years but the complexity and the broad linkage disequilibrium across the region has rendered fine-mapping associations challenging. Novel imputation strategies can now be utilized to impute HLA classical alleles and amino acids across the region. Objectives The aim of this work was to gain a greater understanding of the associations across the HLA region in all JIA subtypes. Methods Using the dense genotype data obtained from the analysis of the Illumina ImmunoChip in 4574 JIA cases (not including the systemic-onset cases) and 14412 controls, we imputed HLA classical alleles (2-digit and 4-digit resolution) and amino acids across the MHC region (Chr6:29-34Mb) using the SNP2HLA algorithm and a large reference panel. We performed univariate analysis for all markers across the region and tested all amino acids in HLA-DRB1 by performing an omnibus test of amino acid residues for each position. Conditional analysis, including the most significant marker as a covariate, was performed to identify independent effects. Analysis was repeated in the individual subtypes (persistent oligoarthritis (pO) n=1751, extended oligoarthritis (eO) n=658, RF negative polyarthritis (RF-P) n=1525, RF positive polyarthritis (RF+P) n=337, enthesitis related arthritis (ERA) n=183, psoriatic arthritis (jPsA) n=112). Results The omnibus test for all amino acids across HLA-DRB1 showed most significant association at HLA-DRB1 amino acid (AA) 67 and conditioning on all residues at AA 67 found significant association remaining at HLA-DRB1 AA 13 (the glycine residue most associated), suggesting two independent effects in HLA-DRB1. There was evidence for further effects in HLA-DRB1. Conditioning on all alleles of HLA-DRB1 found additional independent effects at HLA-DPB1-0201 and HLA-A AA 95. These associations hold across RF-P and both pO and eO subtypes, HLA-DRB1 AA 13 is most strongly associated in RF+P with the histidine residue driving the association. In the ERA subtype HLA-B27 showed the strongest association. For jPsA no HLA markers reached genome-wide significance. Conclusions Analysis of the MHC region in the largest cohort of JIA cases and controls studied to date has found the strongest association with the HLA-DRB1 region, with additional multiple independent effects. Acknowledgements Juvenile Arthritis Consortium for Immunochip (JACI) Disclosure of Interest None declared

Juvenile idiopathic arthritis (JIA) is the most common arthritic disease of childhood and is caused by a combination of genes and environment. In the last few years great advances have been made in dissecting the genetic basis of JIA with now 17 confirmed susceptibility loci identified. One of these loci, the MHC region, has been established for many years but the complexity and the broad linkage disequilibrium (LD) across the region has rendered fine-mapping associations challenging. Novel imputation strategies can now be utilized to impute HLA classical alleles and amino acids across the region.

Background Genome wide association studies (GWAS) have been hugely successful in identifying susceptibility loci for autoimmune diseases. One interesting outcome of GWAS is the observation that many of the loci are shared across these diseases. The regions identified now require more detailed fine-mapping to localize the association signal and identify putative functional variants. The Immunochip consortium was established to pool confirmed loci from 12 diseases onto a custom genotyping chip investigating ∼200 established autoimmune susceptibility loci. For each locus, all known genetic variation from multiple sources was included. Juvenile idiopathic arthritis (JIA) is the most common arthritic disease of childhood. Candidate gene studies have identified a number of common autoimmune genes that confer susceptibility to JIA, however JIA has been less well studied using large-scale approaches. Objectives To use the Immunochip to fine-map previously associated regions and to identifying novel loci for JIA. Methods Genotyping was performed using the Immunochip, in a large cohort from the UK, US and Germany comprising 1749 JIA oligoarthritis and RF negative polyarthritis cases and 8854 controls. All raw genotyping data was combined for clustering and QC. SNPs failed QC based on a call rate <98% and/or cluster separation score <0.4. Samples failed QC based on a call rate <98%. Outliers of mean heterozygosity, related individuals and ancestral outliers were removed. Final sample size after QC was 1609 cases and 7153 controls. Analysis was performed using logistic regression adjusting for the top 5 principal components in PLINK 1.07. Results Initial analysis has not only confirmed previously associated JIA loci (HLA, PTPN22, IL2, STAT4, PTPN2 and SH2B3/ATXN2) but has strengthened their association, such that all now reach genome-wide significance. A number of novel loci have been identified, some of which showed weak evidence previously, such as IL2RA, IL7R and IRF1, and others which have never been associated with JIA, such as RUNX1, FAS and ANKRD55. These will require validation in independent cohorts. Conclusions The Immunochip project enables cost-effective fine-mapping of autoimmune loci in diseases such as JIA. This preliminary analysis has confirmed and strengthened the association of a number of previously associated genes as well as the identification of novel susceptibility loci for JIA. Further analysis of this data will help characterize all associated variants and identify the likely causal variants for future functional studies. Acknowledgements:Childhood Arthritis Prospective Study (CAPS), Childhood Arthritis Response to Medication Study (SPARKS-CHARMS), BSPAR study group, UK JIA Genetics Consortium (UKJIAGC), Cincinnati Registry for Juvenile Arthritis Genetics (CRJAG), Consortium for Juvenile Arthritis Genetics (CJAG), and USA-Juvenile Arthritis Genetics Cohort (USA-JAGC). Disclosure of Interest None Declared

Objective: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune arthropathy. Beta 2-adrenergic receptors are a link between the sympathetic nervous system and the immune system. Associations between variants in the gene encoding the beta 2-adrenergic receptor (ADRB2) and autoimmune disorders such as rheumatoid arthritis (RA) have been demonstrated. We aimed to investigate ADRB2 variants for association with JIA. Methods: Genotypes and haplotypes of two ADRB2 variants (G16R and Q27E) were determined in 348 children with JIA and 448 healthy controls by direct molecular haplotyping using melting-curve analysis of a fluorescently labelled loci-spanning probe. Case-control analysis was performed to investigate whether ADRB2 variants were associated with JIA. Results: No association was found between JIA and alleles, genotypes, or haplotypes of ADRB2. Specifically, the haplotype that demonstrated a strong association with RA (R16/Q27) was not associated with JIA. None of the variants demonstrated association after stratification by JIA subtypes or gender. Conclusions: Our results indicate that ADRB2 variants are not associated with JIA or any of the major JIA subtypes. These observations suggest that, although they share several clinical and pathological features, JIA and RA have unique genetic associations.

To control symptoms and prevent increasing disability in children with active polyarticular Juvenile Idiopathic Arthritis (JIA), long-term, effective treatment that controls all aspects of the disease is necessary. Individual ACR Pedi response criteria were analyzed for the 128 patients who entered the open-label extension (OLE) of the Phase III study of adalimumab in the treatment of polyarticular JIA. Measurements of disease activity were performed at each visit, including active joint count (AJC), number of joints with limitation of passive motion (LOM), parent's or patient's assessment of patient's pain (PaP), disability index of the Children's Health Assessment Questionnaire (CHAQ DI), and physician's global assessment of disease activity (PhDA). Observed data were examined for those patients who had been treated with adalimumab throughout the study and reached more than 1 year in the OLE (Week 56; 75% of entering patients had data available). Patients entering the study had active polyarticular JIA, with clinically significant joint involvement, limitation of motion, pain, and disability in performing daily living activities. Long-term treatment with adalimumab provided marked improvements in disease activity (Table ​(Table1).1). The established safety profile for adalimumab remained consistent. Table 1 Improvements in JIA with adalimumab therapy Long-term treatment with adalimumab substantially improves multiple aspects of polyarticular JIA.

OBJECTIVE:To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care.METHODS:An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease.RESULTS:A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation.CONCLUSION:This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.

Adenosine deaminase (ADA)-deficient Severe Combined Immunodeficiency (ADA-deficient SCID) is characterized by impaired lymphocyte development and function resulting from the adenosine metabolism defect. Enzyme replacement therapy with polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) minimizes infectious complications of ADA-deficient patients who have not received bone marrow transplantation. In PEG-ADA therapy, enzymatically active ADA continuously circulates to act as a metabolic sink, detoxifying the adenosine and deoxyadenosine metabolites that accumulate to high levels in the absence of ADA. Studies have shown that upon the initiation of PEG-ADA therapy, the absolute numbers of circulating T and B lymphocytes and NK cells increase and protective immune function develops. However, the long-term efficacy is unknown. This retrospective study was designed to assess the long-term effectiveness of PEG-ADA treatment, based on evaluation of the immune function of nine ADA-deficient SCID patients (age 5–15) treated over the past decade. The results showed that the lymphocyte counts of all of the PEG-ADA treated patients were below the normal range at all times, despite initial improvements. A gradual decline of mitogenic proliferative responses occurred after a few years of treatment and normal antigenic response occurred less than expected. To this date, these low numbers and functions of lymphocytes had been adequate to provide protective immunity. These patients should be followed closely to detect a premature decline in immune function with aging in future decades of PEG-ADA therapy.

OBJECTIVE:To estimate the degree of familial aggregation of juvenile idiopathic arthritis (JIA), determine whether the aggregation of JIA and the aggregation of type 1 diabetes mellitus (type 1 DM) overlap, and identify multiplex JIA pedigrees.METHODS:Records of individuals with JIA or type 1 DM were probabilistically linked with records in the Utah Population Database (UPDB), a large computerized family history database. For each case of JIA or type 1 DM, 10 matched controls or 5 matched controls, respectively, were selected. All familial relationships among cases of JIA or type 1 DM were established. A familial risk score was calculated for each subject. For various levels of familial exposure to JIA or type 1 DM, one's risk (odds ratio [OR]) of developing JIA or type 1 DM was established (cases compared with controls). Recurrence risks for JIA were computed for relatives of JIA cases compared with relatives of controls. Extended JIA families were identified from a list of common ancestors.RESULTS:Records of a total of 443 patients were linked with the UPDB. Of these, 381 (86.0%) met criteria for JIA. An increased risk for JIA was observed among relatives of probands with JIA. The prevalence of type 1 DM among JIA cases was higher than the US prevalence of type 1 DM (P < 0.003). The recurrence risk for JIA was significantly elevated among first-degree relatives of cases with JIA (OR 30.4). The overall prevalence of JIA was 28/100,000. Four extended JIA pedigrees were identified.CONCLUSION:There is familial aggregation of JIA in the Intermountain West region of the US. We have demonstrated that multiplex JIA pedigrees can be identified using a genealogic database.

The Caribbean reef-building corals Acropora palmata and Acropora cervicornis have undergone widespread declines in the past two decades, leading to their designation as candidates for listing under the United States Endangered Species Act. Whole-reef censuses in 1983 and 2000 at Looe Key National Marine Sanctuary in the Florida Keys provide estimates of areal loss of live Acropora spp. cover. Area (square meters) of live coral cover was quantified from depiction on scaled base maps of extent of coral cover observed by a snorkeler on each reef spur at each census. Certain thickets appear to have been persistent (though none expanded), but the total area of live A. palmata at Looe Key is estimated to have declined by 93% and A. cervicornis by 98% during this 17-year interval. It is likely that acroporid populations may have already undergone substantial decline prior to our initial census in 1983.