PTPN22 R620W polymorphism in the ANCA-associated vasculitides

Objectives. PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism ( SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. Methods. PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. Results. The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, chi(2) = 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, chi(2) = 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, chi(2) = 7.258, OR = 1.98), lung involvement (P = 0.0060, chi(2) = 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, chi(2) = 16.567, OR = 3.73). Conclusion. The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset

The crystal structure of dissakisite-(La) and structural variations after annealing of radiation damage

The crystal chemistry of the new mineral dissakisite-(La), the Mg-analogue of allanite-(La) with ideal formula CaLaAl2MgSi3O12(OH), was studied by single-crystal X-ray diffraction and Mossbauer spectroscopy. Diffraction data indicated that it has a partially metamict state with expanded cell parameters a = 8.959, b = 5.7226, and c = 10.232 angstrom, beta = 115.19 degrees, and V = 474.7 angstrom(3). The crystal structure was refined to R(I/sigma(I) > 4) of 3.45% and wR2 of 8.52% (S.G. P2(1)/m). The displacement parameters are unusually large as consistent with positional disorder. Ca and REE are partitioned between the A1 and the A2 sites, Fe2+ between the M3 and the Al sites, and Fe3+ between the M3 and the M2 sites. Th is confined to A1. The Mossbauer spectrum implies the presence of five different iron sites, three Kof which are attributed to Fe2+ at the M3 site, one to Fe2+ at the A1 site, and one to Fe3+ at a rather distorted octahedral site. Annealing at 700 degrees C caused contraction of cell edges (b and c shrank by 0.5%, a by 0.3%, beta only slightly decreased; similar to 1% in V) and of bond distances, with a consequent overall increase in bond valences. Displacement parameters decreased by about 30%, leading to a significant increase from 1495 to 1627 in the number of reflections with I/sigma(I) > 4. Structure rearrangement was achieved by means of flexible points such as the two-coordinated oxygen atoms 08 and 09, and by greater volume decreases in M3, A1, A2, and Si3 polyhedra. Si tetrahedra behaved non-rigidly, at variance with what was observed for isomorphous substitution and thermal expansion. Despite the high Th content and the age of the mineral, the crystal structure is well preserved. The above paradox could be explained by a thermal event after formation of the mineral that reversed previous damage, or by a prolonged period under relatively high-temperature conditions

Fatal exacerbation of systemic lupus erythematosus after induction of ovulation.

It is well known that sex hormones can regulate the course of systemic lupus erythematosus (SLE). We describe a young woman who had a fatal exacerbation of SLE after controlled ovarian hyperstimulation for induction of ovulation. We recommend careful attention to the immunological status of the infertile women before starting any ovulation inducing treatment for assisted reproduction

[The Reynolds syndrome. Clinical case and review of the literature. Analogy with graft-versus-host disease]

The Reynolds syndrome. Clinical case and review of the literature