HLA-NET (a European COST Action) aims at networking researchers working in bone marrow transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human populations, with an expected strong impact on both public health and fundamental research. Such improvements involve finding consensual strategies to characterize human populations and samples and report HLA molecular typings and ambiguities; proposing user-friendly access to databases and computer tools and defining minimal requirements related to ethical aspects. The overall outcome is the provision of population genetic characterizations and comparisons in a standard way by all interested laboratories. This article reports the recommendations of four working groups (WG1-4) of the HLA-NET network at the mid-term of its activities. WG1 (Population definitions and sampling strategies for population genetics’ analyses) recommends avoiding outdated racial classifications and population names (e.g. ‘Caucasian’) and using instead geographic and/or cultural (e.g. linguistic) criteria to describe human populations (e.g. ‘pan-European’). A standard ‘HLA-NET POPULATION DATA QUESTIONNAIRE’ has been finalized and is available for the whole HLA community. WG2 (HLA typing standards for population genetics analyses) recommends retaining maximal information when reporting HLA typing results. Rather than using the National Marrow Donor Program coding system, all ambiguities should be provided by listing all allele pairs required to explain each genotype, according to the formats proposed in ‘HLA-NET GUIDELINES FOR REPORTING HLA TYPINGS’. The group also suggests taking into account a preliminary list of alleles defined by polymorphisms outside the peptide-binding sites that may affect population genetic statistics because of significant frequencies. WG3 (Bioinformatic strategies for HLA population data storage and analysis) recommends the use of programs capable of dealing with ambiguous data, such as the ‘gene[rate]’ computer tools to estimate frequencies, test for Hardy–Weinberg equilibrium and selective neutrality on data containing any number and kind of ambiguities. WG4 (Ethical issues) proposes to adopt thorough general principles for any HLA population study to ensure that it conforms to (inter)national legislation or recommendations/guidelines. All HLA-NET guidelines and tools are available through its website http://hla-net.eu.

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This work was carried out in collaboration between all authors. Author EE performed HLA typing, analysed data, wrote the report. Author EH was involved in collection of date and in revision of manuscript. Author JP planned the study, wrote the protocol, collected and analysed clinical data. Author IG was responsible for study planning, collection and analysing of data, she was involved in practical clinical aspects. Author LE was involved in practical clinical aspects. Authors DG and AS were involved in study planning. All authors read and approved the final manuscript.

Background Juvenile idiopathic arthritis (JIA) is heterogenous group of diseases and it is most common rheumatic disease in children. Inflammatory cytokines and their regulatory gene polymorphisms are important in the pathogenesis of JIA. Interleukin 6 (IL-6) is significant in inflamation [1] whereas IL-10 has anti-inflammatory activity [2]. Protein tyrosine phosphatase non-receptor 22 (PTPN22) has impact on T and B cell regulation and activation [3]. One single nucleotide polymorphisms (SNP) substitution within certain gene can affect cytokine production, T and B cell regulation, inflammatory processes and disease outcome. Objectives To determine the association of IL-6, IL-10 and PTPN22 gene SNP with JIA. Methods All 40 JIA patients (19 seronegative and 5 seropositive polyarthritis, 10 persistent and 6 extended oligoarthritis) and 20 healthy controls were determined for IL-6 gene promoter polymorphisms in –174GG, -174GC and –174CC positions, IL-10 gene promoter SNP in -(1082A), -(819T) and -(592A)positions, as well as the PTPN22 gene C1858T polymorphism for genotypes T/T and T/T + C/T. The sample genetic analysis was performed using real-time polymerase chain reaction (RT-PCR) for DNA tipping technique with TaqMan SNP genotyping probes (QuantiFast Probe RT-PCR Kit Plus Applied Biosystems). Each potential SNP genotype distribution was compared between the different types of JIA and control group using chi-square test and Fisher’s exact test. Results We found significant differences in IL-6 -174GC genotype distribution between JIA patients and controls (OR=2,05; p<0,031). Among JIA subtypes IL-6 SNP in -174GG and -174CC positions has no significant differences (p<0,36), but –174GC position was more common in seronegative polyarthritis JIA patients (OR=0,41, p<0,005). Certain haplotypes GCC, ACC and ATA for three IL-10 promoter SNPswere investigated. JIA patients compared to controls, demonstrated significantly higher IL-10 ATA/GCC and GCC/GCC haplotype distribution (p=0,005 and p=0.02). Comparing IL-10 promoter SNPs between JIA subtypes, no significant differences were found (p=0,36), which is probably due to the small number of patients. The PTPN22 C1858T SNPs for C/T genotype was significantly higher in JIA group (OR=1.36, p<0,035). Comparing PTPN22 C1858T SNPs genotypes between JIA subtypes no significant differences were found. Conclusions 1. IL-6 SNP –174G/C was more common in JIA seronegative polyarthritis. 2. JIA patients demonstrated higher IL-10 ATA/GCC and GCC/GCC haplotypes distribution 3. PTPN22 C1858T C/T genotype was seen more common in JIA. 4. To obtain more accurate data on the regulatory cytokine gene polymorphisms in the pathogenesis of JIA, additional studies are need. References K.Oen et al.: Cytokine genotypes correlate with pain and radiologically defined joint damage in patients with juvenile idiopathic arthritis. Rheumatology 2005 Sep;44(9):1115-21. J.C.Moller et al.: IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA). Clin Exp Rheumat...