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International audience; In this review, we present for the first time an integrated version of the Gene[rate] computer tools which have been developed during the last 5 years to analyse human leukocyte antigen (HLA) data in human populations, as well as the results of their application to a large dataset of 145 HLA-typed population samples from Europe and its two neighbouring areas, North Africa and West Asia, now forming part of the Gene[va] database. All these computer tools and genetic data are, from now, publicly available through a newly designed bioinformatics platform, HLA-net, here presented as a main achievement of the HLA-NET scientific programme. The Gene[rate] pipeline offers user-friendly computer tools to estimate allele and haplotype frequencies, to test Hardy-Weinberg equilibrium (HWE), selective neutrality and linkage disequilibrium, to recode HLA data, to convert file formats, to display population frequencies of chosen alleles and haplotypes in selected geographic regions, and to perform genetic comparisons among chosen sets of population samples, including new data provided by the user. Both numerical and graphical outputs are generated, the latter being highly explicit and of publication quality. All these analyses can be performed on the pipeline after scrupulous validation of the population sample's characterisation and HLA typing reporting according to HLA-NET recommendations. The Gene[va] database offers direct access to the HLA-A, -B, -C, -DQA1, -DQB1, -DRB1 and -DPB1 frequencies and summary statistics of 145 population samples having successfully passed these HLA-NET 'filters', and representing three European subregions (South-East, North-East and Central-West Europe) and two neighbouring areas (North Africa, as far as Sudan, and West Asia, as far as South India). The analysis of these data, summarized in this review, shows a substantial genetic variation at the regional level in this continental area. These results have main implications for population genetics, transplantation and epidemiological studies.

Sequence-based typing procedure (SBT) procedure permitted us to identify a new human leukocyte antigen-A allele in a patient attending hematopoietic stem cell transplantation.

Breve descrizione del prodotto: Studio di due marcatori genetici (BDNF e HLA-DR) in un gruppo di bambini affetti da malattie neuropsichiatriche (ADHD e ritardo mentale) allo scopo di evidenziare una eventuale correlazione tra alcuni genotipi e la predisposizione/protezione verso la patologia.

Anthropology/Human HLA Genetic Diversity Population Reports. Population: Metalsa from Morocco.

Anthropology/Human Genetic Diversity Population Reports. Population: Chaouya from Morocco.

We analysed the specific effects of IL-1beta immunoneutralization on the expression of IL-6 in different pure cultures of neurones and glia after both experimental subliminal hypoxia and recovery. Whereas the IL-1beta-deprivation signal induced a decrease in IL-6 expression and release of normoxic neurones, it provoked an increase in IL-6 protein in hypoxic neurones. Moreover, the direct correlation between IL-1beta and IL-6, observed in normal and recovering neuronal cultures, was reversed in hypoxic conditions. These reversals were not observed in glial cells, in which IL-1beta immunosuppression led to a decrease in IL-6 under all conditions considered. In conclusion, the IL-1beta modulates IL-6 in different ways according to the ambient physiological or pathological conditions, and also acts via different mechanisms, depending on the cellular phenotype.

To examine the genetic diversity in Morocco, the polymorphism at the HLA-DRB1 locus was investigated in two populations: the Metalsa group consisting of Berbers from north Morocco (who speak the Tarifit language and live in the Nador area), and the Chaouya group who are Arabic-speaking people from west Morocco (Atlantic coast) living in the Settat area. The DRB1 alleles of 197 healthy unrelated individuals were identified by direct DNA sequencing of exon 2 using fluorescently-labeled primers. A total of 28 and 29 alleles at DRB1 locus were identified in the Metalsa and Chaouya groups, respectively. The most frequent alleles in the Metalsa group are DRB1*03011 (20.2%), DRB1*0701 (12.12%), and DRB1*1302 (11.11%). In the Chaouya group, DRB1*0701 (16.33%), DRB1*15011 (12.76%), and DRB1*03011 (11.73%) are most common. Each population exhibits some specific variants and some uncommon alleles. The frequency of the DRB1*03011 allele differs significantly between the two populations (p = 0.0311). The DRB1 frequency distributions in the two groups suggest the effects of balancing selection. The interpopulation analysis highlighted a strong relatedness, based on genetic distances, between the two Moroccan groups and the other north Africans (the Moroccans from El Jadida area, Moroccan Souss Berbers, Algerians, and Tunisians), and to a lesser extent with the Iberians, French, and Ethiopians.

This report presents a novel allele, HLA-B*4427, which was identified in a bone marrow donor of Caucasian origin, and a confirmatory sequence (B*44022). Sequence analysis revealed the new allele differs from B*44021 by a single nucleotide exchange at position 668 (C®T), which is located in exon 4. At the protein level, it is the only B*44 variant to produce an Ala in place of a Val at codon 199. Its structure suggests that it may have originated from a point mutation in B*44021 or by gene conversion with a variety of HLA-B alleles. Cloning and sequencing of the allele B*44022 revealed a sequence identical to B*44021 and B*44 exon 4, with the codon GTC (Val) in position 199.

Investigation at high resolution of the polymorphism of the HLA-A and B loci in two populations from Morocco, named Metalsa and Chaouya.

In order to study the effector and regulatory functions of lymphocytes in mood disorders, bipolar type, the production of Interleukin 2 (IL-2), soluble receptor of IL-2 (IL-2R), Interleukin 6 (IL-6) and Tumor Necrosis Factor (TNF) were assayed in serum of bipolars, schizophrenics and healthy subjects. The study failed to find out any difference regarding lymphokine production in mental disorders.

Immunological evaluations on cancer patients provide informations to understand the disregulations which allow the tumor to locate and progress in the host. In colon cancer patients and controls we examined the serum levels of various cytokines and the proliferative response of PBMC to IL-2, IL-4, anti-CD3mAb. Our results show that in patients there was a significant serum increase of IFN?, IL-4, IL-6, whereas IL-2 significantly decreases. This situation is indicative for the functional presence of inflammatory CD4+TH2 cells. In patients it is possible to note a negative correlation between the proliferative response to IL-2 and stage of the disease (*P = 0.0024), which changes into positive when anti-CD3 is added (*P = 0.007) (indicative for a functional increase of CD4+TH2 cells with the disease progression). Moreover in patients the proliferative response to IL-2 + anti-CD3 was comparable to controls (§P = 0.42), whereas in the former there wasa significant reduction after IL-4 addition (§P = 0.005). This effect of IL-4 on IL-2 + anti-CD3 starts at stage II, whereas at stage I the response is still comparable to controls and there is a greater response to IL-2 alone (§P = 0.0035). Analysing our data, it seems that the start of the immunological response in patients is of inflammatory type and it degenerates because IL-4, which raises with the disease progression, interferes with IL-2 mechanisms.

Soluble interleukin-2 receptor (sIL-2R) levels have been found to be elevated in several clinical conditions, including disseminated solid neoplasms, whereas they are generally within the normal range in patients with locally limited neoplastic disease. The aim of the present study was to examine this in our colon cancer patients, and to assess if this situation can affect the in vitro activation of peripheral blood mononuclear cells (PBMC) examining the proliferative response to IL-2 and anti-CD3 monoclonal antibody, the IL-2 serum levels and the PBMC phenotype. The results show that sIL-2R levels were significantly correlated with the stage of the disease, showing an increase from stage I to stage IV; moreover, it is worth noting that the proliferative response to IL-2 plus anti-CD3 is significantly higher than to IL-2 alone in stage IV, without significant alteration in the numerical presence of T and natural killer cells. So it seems that in the peripheral blood of patients, connected with the disease progression, are present cellular populations showing a different response to activation, and that T cells acquire a better response condition than NK. Thus, since the T cellular population includes the tumour-specific cytotoxic precursor cells, this should be helpful for its tumour regressive activity, but it is conceivable that this population cannot perform its functions, owing to a deficiency in responsiveness of the specific ThCD4+ subpopulation. © 1994 Springer-Verlag.

In immunotherapeutic treatments it is not clear why their effectiveness is only limited to treatment of some neoplasms and patient kind. For the potential development of effective methods of cancer immunotherapy is important understanding the interaction with the immune system. In colon cancer we examined the sIL-2R, IL-2, IL-6 and TNF serum levels; the phenotype of PBMC and Tumor-draining limph node lymphocytes (LML); the proliferative response of PBMC to IL-2, and IL-2+anti-CD3 monoclonal antibody. The correlations with sIL-2R and stage were evaluated. The results are an explanation of the variable clinical response to immunotherapy: 1) if the disease progression is related to alterations in cellular responsive condition it is necessary to value that in every patient to choose the right treatment; moreover 2) because there is also a better condition of T activation response than NK cells, the therapeutic treatments can be successful only when adressed to potentiation of T cellular population and can exclude the immunosuppression effect which can prevent triggering and expansion of T lymphocytes in patients.

Risposta delle colture linfocitarie mista mono-bidirezionali e compatibilità degli antigeni HLA in coppie correlate donatore ricevente trapianto di midollo.