PRF1 mutation alters immune system activation, inflammation, and risk of autoimmunity.

Defective alleles within the PRF1 gene, encoding the pore-forming protein perforin, in combination with environmental factors, cause familial type 2 hemophagocytic lymphohistiocytosis (FHL2), a rare, severe autosomal recessive childhood disorder characterized by massive release of cytokines-cytokine storm. The aim of this study was to determine the function of hypomorph PRF1:p.A91V g.72360387 G > A on multiple sclerosis (MS) and type 1 diabetes (T1D). We cross-compare the association data for PRF1:p.A91V mutation derived from GWAS on adult MS and pediatric T1D in Sardinians. The novel association with T1D was replicated in metanalysis in 12,584 cases and 17,692 controls from Sardinia, the United Kingdom, and Scotland. To dissect this mutation function, we searched through the coincident association immunophenotypes in additional set of general population Sardinians. We report that PRF1:p.A91V, is associated with increase of lymphocyte levels, especially within the cytotoxic memory T-cells, at general population level with reduced interleukin 7 receptor expression on these cells. The minor allele increased risk of MS, in 2903 cases and 2880 controls from Sardinia p = 2.06 × 10 <sup>-4</sup> , odds ratio OR = 1.29, replicating a previous finding, whereas it protects from T1D p = 1.04 × 10 <sup>-5</sup> , OR = 0.82. Our results indicate opposing contributions of the cytotoxic T-cell compartment to MS and T1D pathogenesis

Meson spectroscopy with the OBELIX apparatus

The main features of the coupled channel analysis and some physical results of the annihilation reaction at rest pp -+ 1("+1("-1("0, K+K-1("° and K±K~1("'F at three different target densities are discussed

Measurement of the anti-p p annihilation cross-sections at very low energies

The annihilation cross-sections at 66.4-68.9-71.4 MeV/c have been measured using the presently instrumented part of the OBELIX spectrometer. The results have been obtained at energies ( ≃ 2.5 MeV) by one order of magnitude smaller than in any existing experiment concerning the in-flight antiproton-proton annihilation. The average value obtained over the total interval 65.1-72.5 MeV/c, βσanT = 33.2 ± 1.7 (stat.) ±1.8 (syst.) mb, in agreement with a specific calculation, would favour for the spin-averaged S-wave scattering length the value (−0.7 + i0.8) fm. The branching ratios for the annihilations in two, four and six charged mesons turn out to be quite similar to those for annihilation at rest in liquid hydroge