Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes1, with epidemiologic association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment.

Table of contentsP001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP effluxR. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. EllisP002 - Lower serum immunoglobulin G2 level does not predispose to severe flu.J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez GallegoP003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsisF. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. TuzunP004 - Adenosine a1 receptor dysfunction is associated with leukopenia: A possible mechanism for sepsis-induced leukopeniaR. Riff, O. Naamani, A. DouvdevaniP005 - Analysis of neutrophil by hyper spectral imaging - A preliminary reportR. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. ShimazuP006 - Chemiluminescent intensity assessed by eaa predicts the incidence of postoperative infectious complications following gastrointestinal surgeryS. Ono, T. Kubo, S. Suda, T. Ueno, T. IkedaP007 - Serial change of c1 inhibitor in patients with sepsis – A prospective observational studyT. Hirose, H. Ogura, H. Takahashi, M. Ojima, J. Kang, Y. Nakamura, T. Kojima, T. ShimazuP008 - Comparison of bacteremia and sepsis on sepsis related biomarkersT. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. OnoP009 - The changes of procalcitonin levels in critical patients with abdominal septic shock during blood purificationT. Taniguchi, M. OP010 - Validation of a new sensitive point of care device for rapid measurement of procalcitoninC. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. LottP011 - Infection biomarkers in primary care patients with acute respiratory tract infections – Comparison of procalcitonin and C-reactive proteinM. M. Meili, P. S. SchuetzP012 - Do we need a lower procalcitonin cut off?H. Hawa, M. Sharshir, M. Aburageila, N. SalahuddinP013 - The predictive role of C-reactive protein and procalcitonin biomarkers in central nervous system infections with extensively drug resistant bacteriaV. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. MichaloudisP014 - Changes in endotoxin activity assay and procalcitonin levels after direct hemoperfusion with polymyxin-b immobilized fiberA. Kodaira, T. Ikeda, S. Ono, T. Ueno, S. Suda, Y. Izutani, H. ImaizumiP015 - Diagnostic usefullness of combination biomarkers on ICU admissionM. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-AlcantaraP016 - Platelet function analysis utilising the PFA-100 does not predict infection, bacteraemia, sepsis or outcome in critically ill patientsN. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. NeeP017 - Extracellular histone H3 levels are in...

Prostaglandins and their analogues are beneficial as topical agents in vitiligo treatment, yet neither of the previous study addressed their comparative efficiency with conventional topical agents used in vitiligo treatment. In this pilot (24 patients) left-right comparative study we addressed efficiency of prostaglandin F2α analogue latanoprost versus tacrolimus when combined with narrow-band ultraviolet B and microneedling in repigmentation of nonsegmental vitiligo lesions. Our results confirm potency of prostaglandins, in particular, that of latanoprost, in inducing repigmentation, with the efficiency being at least comparable to that of tacrolimus, while contribution of microneedling remains unclear. In summary, results of our study provide further evidences for justified use of prostaglandins, in particular, latanoprost, in vitiligo treatment. In turn, this warrants future studies on the topic aiming to conclusively introduce prostaglandin-based formulations as conventional agents for vitiligo management.

We investigated the expression of butyrophilin in eukaryotic cells with a view to determining the number of mRNA species, the incorporation of the peptide chain into microsomes, and the topology of the processed protein in biological membranes. Butyrophilin is synthesized from a single sized mRNA in both bovine and murine lactating mammary tissue and associates with microsomal membranes with a type I topology (N exo ⅐C cyto ) via a single hydrophobic anchor in the middle of the sequence. Several isoelectric variants of the protein were detected in cellular membranes from lactating bovine mammary tissue and in the milk-fat-globule membrane. We found no evidence for soluble forms of butyrophilin in postmicrosomal supernatants. The 66-kDa protein appears to be subjected to limited proteolysis, giving rise to a 62-kDa fragment lacking the C terminus and to other more minor fragments of lower M r in the milk-fat-globule membrane. Antipeptide antibodies to epitopes within the N-and C-terminal domains were used to show that butyrophilin retains a type I topology in plasma membranes when expressed in insect cells from a baculovirus vector, and in secreted milk-fat globules. These data do not agree with previous suggestions that butyrophilin may exist in cytoplasmic soluble forms, or be reorganized in the plane of the lipid bilayer during secretion in lipid droplets from mammary cells. The results are discussed with reference to the role butyrophilin may play as the principal scaffold for the assembly of a complex with xanthine oxidase and other proteins that functions in the budding and release of milk-fat globules from the apical surface during lactation.Several years ago we cloned a cDNA encoding the major milk-fat-globule membrane (MFGM) 1 protein, butyrophilin (BTN) (1) with a view to understanding the function of this mammary-specific protein in milk-fat secretion (for reviews of this process, see Refs. 2-4). From the derived amino acid sequence we predicted that BTN is an integral protein with a single membrane anchor and a glycosylated exoplasmic N terminus (type I orientation) (1). Subsequent comparisons with more recently cloned cDNAs have established that BTN is a member of the immunoglobulin superfamily (5) with two Nterminal immunoglobulin domains, one of the intermediate type (IgI) (6) toward the N terminus and one of the constant C1 type (7) toward the membrane bilayer (8). A large proportion of the C-terminal region comprises the RFP or B30.2 domain, a sequence which is present in a subfamily of zinc-finger proteins (9, 10), and a group of recently identified BTN-like genes (11, 12). Several workers have proposed that BTN may function as an integral receptor for cytoplasmic fat droplets and that budding of the droplets at the cell surface is initiated by interactions between the cytoplasmic tail of BTN and other proteins, notably the redox enzyme xanthine oxidase (1, 13-16). However, the assumption that BTN behaves as an integral protein in mammary epithelial cells has been confounded by several observati...

Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length-assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26-50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB-UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant-to-treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification.

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