To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA—associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.

Data from Slovene national primary immunodeficiency (PID) registry are presented. Besides clinical and genetic data of patients with PID, quality indicators in patient care are included. Data are systematically collected in Department of Allergology, Rheumatology and Clinical Immunology in collaboration with physicians of different specialities. Increasing number and spectrum of PID are recognised in Slovenia. After establishment of Slovene multidisciplinary group in PID care in 2007 thorough immunological and genetic diagnostics, subcutaneous immunoglobulin replacement and treatment of PID with haematopoietic stem cell transplantation were introduced in routine clinical practice in Slovenia. Increased medium age of PID patients reflects improved survival and better recognition of PID in adults. According to the data in comparable registries percentages of patients with predominantly antibody deficiencies and complement deficiencies are low and high, respectively.

Objective To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre-MAS visit and at MAS onset, and the change in values between the two time points. The experts were asked to choose the 5 laboratory tests in which change was most important for the diagnosis of MAS and to rank the 5 selected tests in order of importance. The relevance of change in laboratory parameters was further discussed and ranked by the same experts at a consensus conference. Results Platelet count was the most frequently selected test, followed by ferritin level, aspartate aminotransferase (AST), white cell count, neutrophil count, and fibrinogen and erythrocyte sedimentation rate. Ferritin was most frequently assigned the highest score. At the end of the process, platelet count, ferritin level and AST were the laboratory tests in which the experts found change over time to be most important. Conclusions We identified the laboratory tests in which change over time is most valuable for the early diagnosis of MAS in sJIA. The dynamics of laboratory values during the course of MAS should be further scrutinised in a prospective study in order to establish the optimal cut-off values for their variation.

OBJECTIVES Familial Mediterranean fever (FMF) is an autosomal-recessive disorder caused by mutations in MEFV gene. Eastern Mediterranean populations have the highest number of carriers, whereas western Mediterranean populations are less frequently affected. The aim of this study was to determine the carrier rate and spectrum of MEFV gene mutations in apparently healthy populations and in suspected FMF patients from central and southeastern European (CSEE) countries. METHODS We screened 507 apparently healthy persons from 5 CSEE countries. Exons 2 and 10 of the MEFV gene were PCR amplified and subsequently sequenced with ABI prism310 genetic analyser. Six most common mutations in the MEFV gene were tested: V726A, K695R, M694V, M694I, M680I in exon 10, and E148Q in exon 2. In suspected FMF patients we screened all MEFV exons in selected cases. RESULTS The overall carrier frequency of all MEFV mutations was higher than expected (9.3%). In the whole cohort we did not find any apparently healthy persons with two mutations. Heterozygous mutations were found in apparently healthy subjects from different CSEE countries as follows: Macedonia 16%, Serbia 11%, Bosnia and Herzegovina 8%, Slovenia 6% and Hungary 5%. The most common mutation in healthy controls was K695R, appearing in 40% of mutated alleles. The most common mutation in suspected FMF patients was M694V, followed by K695R. CONCLUSIONS We found a higher than expected carrier rate of MEFV gene mutations in populations from CSEE countries. It is interesting to note that 40% of detected carriers carry the K695R mutation.

The dynamic process of the development of the immune system can in itself result in age-related immune malfunctions. In this study, we analysed lymphocyte subsets in the peripheral blood of 60 healthy donors, divided into groups of children, adolescents, and adults, focusing on effector (Teff) and regulatory (Treg) T lymphocytes and STAT1/STAT5 signalling response in helper T lymphocytes (Th) in adults, using flow cytometry. Our results demonstrate a decrease in the percentage of total Tregs and an increase in the percentage of total Teffs with age and a consequential immense increase in the Teff/Treg ratio. The increase of Teffs was most apparent in Th1, Th1Th17, and Th17CD161− subsets. Significant Th lymphocyte STAT1 expression differences were observed between children and adolescents, which were associated with the decrease in activated Tregs. Higher expression of STAT1 was found in FoxP3hi than in FoxP3low Th lymphocytes, while significant IL-2 induced STAT5 phosphorylation differences were found among the subsets of Th lymphocytes in adults. Our study demonstrates age-related changes in circulating Teff and Treg, as well as significant differences in STAT5/STAT1 signalling among FoxP3+ Th lymphocytes, providing new advances in the understanding of immunosenescence.

Background Currently, the classification of APS is based on clinical and laboratory criteria originally published in 1999 (Sapporo classification) [1] and updated in 2006 [2]. Objectives To assess the need for new APS classification criteria. Methods Based on the Task Force (TF) reports of the 14th International Congress on Antiphospholipid Antibodies (aPL) (September 2013, Rio de Janeiro, Brazil), a new Task Force on “APS Diagnostic and Classification Criteria” has been created under the auspices of the 15th International Congress on aPL (September 2016, Istanbul, Turkey). Members were selected based on their roles as chairs of previous TFs or interested scientific planning committee members. The chairs of this new TF designed a 14-question needs-assessment survey, which was emailed to 13 members in August 2014. Responses were analyzed anonymously in a descriptive fashion. Results Survey response rate was 100%. 92% of survey participants reported the need for new ACR classification criteria; 100% agreed that all disease domains are not sampled by current criteria, particularly related to non-criteria APS manifestations; 85% reported scenarios in which current criteria disagree with expert diagnoses; and 62% agreed that other aPL tests should be part of the criteria. Scenarios in which expert diagnoses disagreed with current criteria included: 1) patients with non-criteria manifestations only (with or without positive aPL tests); 2) non-criteria obstetrical findings in patient with positive aPL tests; 3) high suspicion for APS in patients with lack of “persistence” of aPL tests, or negative to low titer aPL tests. Major limitations of the current criteria reported by the responders included: 1) no inclusion of non-criteria clinical manifestations and aPL tests; 2) no evidence based pregnancy morbidity definition; 3) no risk stratification based on aPL-profiles and other co-morbidities; and 4) unclear definition of aPL “persistence”. Conclusions Broad consensus exists among surveyed international APS physician scientists regarding the need for new APS classification criteria. Based on these findings, the Task Force on APS Diagnostic and Classification Criteria is spearheading an effort to prepare new APS Classification Criteria. References Wilson W, Gharavi A, Koike T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309–11. Miyakis S, Lockshin M, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306. Disclosure of Interest M. Barbhaiya: None declared, M. Abreu: None declared, M. Amigo: None declared, T. Avcin: None declared, M. Bertolaccini: None declared, W. Branch: None declared, P. de Groot Grant/research support from: Thrombosestichting, the Netherlands, Consultant for: SynapseBV, Maastricht, the Netherlands, G. de Jesus: None declared, R. Levy: None declared, M. Lockshin: None declared, M. Tektonidou: None declared, D. Wahl: None declared, R. Willis Employee of: Louisville APL DIagnostic Inc., S. Zuily: None declared, K. Costenbader: None declared, D. Erkan: None declared

Background Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Currently just retrospective data exist regarding evolvement of organ involvement. In the previous retrospective studies assessment of the organ involvement was not standardized. Our project is the first one, where data of jSSc patientes were collected prospectively and with a standardized assessment. Objectives To learn about the characteristics and evolvement of organ involvement in jSSc Methods Patients with jSSc were recruited worldwide and were prospectively assessed, using the proposed standardized patient assessment protocol. Data of the juvenile systemic sclerosis inception cohort have been contributed to the DeSScipher project which was funded by a grant of theEuropean Community's Framework Programme 7 under grant agreement N° 305495.” Results 44 centers from 24 countries aggreed to participate on the project. The assent and consent forms were translated into the local native languages. Untill now 39 patients have been enrolled with a mean disease duration of 6.1 years. Thirty (77%) of the 39 patients were females. The mean age of the onset of Raynaud's phenomenon was 9.7 years (2-16 years), the youngest 2 years old. The mean age at the onset of the non-Raynaud presentation of jSSc was 10.3 years (3.0-16.00years). 29 (74%) of the 39 have diffuse subtype. 5 in the diffuse (17%) and 3 in the limited subtype (30%) had an overlap feature. At the time of the inclusion the mean modified Rodnan Skin Score was 16.5. 26/37 had already capillary changes and 22/37 already history of ulcerations, 9/37 had active ulcerations at the time of the inclusion. 26/39 had cardiopulmonary involvement, 11/39 presented with signs of interstitial lung disease on imaging. Two patients had pulmonary hypertension. Three had renal involvement, but no renal crisis. 16/39 had gastrointestinal involvement and 11 of them esophageal involvement. 30/38 had musculoskeletal involvement. ANA positivity occurred in 30/36 and 12/30 of them were anti-Scl 70 positive. 1/23 had anticentromere positivity. Conclusions We present the data on the first 39 patients with jSSc included in our cohort. The current recruitment data confirms that pediatric patients are different from the adult patients, with a higher proportion of diffuse subset patients with 74% and of patients with overlap features. Disclosure of Interest None declared