Allogeneic islet transplantation is limited by adverse effects of chronic immunosuppression used to control rejection. The programmed cell death 1 pathway as an important immune checkpoint has the potential to obviate the need for chronic immunosuppression. We generated an oligomeric form of programmed cell death 1 ligand chimeric with core streptavidin (SA-PDL1) that inhibited the T effector cell response to alloantigens and converted T conventional cells into CD4 + Foxp3 + T regulatory cells. The SA-PDL1 protein was effectively displayed on the surface of biotinylated mouse islets without a negative impact islet viability and insulin secretion. Transplantation of SA-PDL1-engineered islet grafts with a short course of rapamycin regimen resulted in sustained graft survival and function in >90% of allogeneic recipients over a 100-d observation period. Long-term survival was associated with increased levels of intragraft transcripts for innate and adaptive immune regulatory factors, including IDO-1, arginase-1, Foxp3, TGF-b, IL-10, and decreased levels of proinflammatory T-bet, IL-1b, TNF-a, and IFN-g as assessed on day 3 posttransplantation. T cells of long-term graft recipients generated a proliferative response to donor Ags at a similar magnitude to T cells of naive animals, suggestive of the localized nature of tolerance. Immunohistochemical analyses showed intense peri-islet infiltration of T regulatory cells in long-term grafts and systemic depletion of this cell population resulted in prompt rejection. The transient display of SA-PDL1 protein on the surface of islets serves as a practical means of localized immunomodulation that accomplishes sustained graft survival in the absence of chronic immunosuppression with potential clinical implications.
suPAR and IP-10 were able to distinguish between significant and mild fibrosis with good sensitivity and specificity, and may thus represent useful biomarkers for identifying patients with significant fibrosis.
DFS pattern detected by IIF and isolated anti DFS70 antibody positivity detected by IB show high concordance. However IIF results should be confirmed because of the patterns that can be misidentified as DFS pattern. The presence of anti-DFS70 antibodies, which help to exclude SARD, prevent further unnecessary referral demands.
Aim: Tuberculin skin test (TST) is still used in diagnostic algorithms of childhood tuberculosis (TB). QuantiFERON TB Gold In-Tube assay (QFT-GIT) is an alternative test to TST based on the detection of interferon-gamma release upon in vitro induction of peripheral mononuclear cells by TB antigens. In this study, we aimed to determine the diagnostic value and performance of QFT-GIT for active childhood TB. Methods: This retrospective study was conducted between January 2005 and December 2011 in three referral hospitals in Turkey with 124 children who were diagnosed with definite active TB. Sensitivity values of TST and QFT-GIT were determined by accepting the microbiological confirmation as the gold standard of diagnosis of TB. Results: In our study, sensitivity of QFT-GIT and TST was found to be 65 and 66% respectively. However, combined usage of QFT-GIT and TST was found to be more sensitive (85%) than TST or QFT-GIT alone (P < 0.0001). Although negative results of QFT-GIT or TST did not exclude the diagnosis of active TB in children, their positivity supported the diagnosis. Specificity could not be measured as only microbiologically confirmed cases of Mycobacterium tuberculosis disease were enrolled in the study. Conclusion: Although sensitivities of TST and QFT-GIT are too low to exclude active TB, their positivity supports diagnosis of active TB in children concomitant with signs and symptoms. QFT-GIT and TST should be used together to enhance diagnostic sensitivity and could help exclude a diagnosis of TB if the pretest probability is low.
Aralık 2019'da Çin'in Wuhan şehrinde, yeni bir koronavirüs nedeniyle bir salgın başladı ve hızla dünyaya yayıldı. Bu virüs son yirmi yılda iki önemli salgına neden olmuş olan şiddetli akut solunum sendromu (SARS) ve Ortadoğu solunum sendromunun (MERS) etkeni olan beta koronavirüsler ile genomik yapısı, yayılımı, patogenezi açısından benzeyen SARS-CoV-2'dir. Bu derleme, tüm dünyaya yayılmış koronavirüs hastalığı 2019 (COVID-19) salgınına odaklanarak SARS-CoV-2'yi test etmek için mevcut laboratuvar yöntemlerini gözden geçirmektedir. SARS-CoV-2'nin hızlı ve kesin laboratuvar tanısı, karantina önlemlerinin erken alınarak, hastalara tedavileri planlanıp, salgının yayılımını önlemek için gereklidir. Viral pnömoniler pürülan balgam üretimiyle sonuçlanmadığı için, nazofaringeal sürüntü örneği en sık kullanılan yöntemdir. SARS-CoV-2'yi moleküler yöntemlerle test ederken nazofaringeal örnekler bazı vakaları atlayabilir; bu nedenle bronkoskopi ile daha derin bir örnek alınması gerekebilir. Ama bronkoskopi oluşturduğu aerosol nedeniyle sağlık çalışanlarına bulaş açısından daha risklidir. Bunun yerine yinelenen nazofaringeal örnekleme yapılabilir, çünkü zamanla nazofarenkste SARS-CoV-2 bulunma olasılığı artar. Antikor testleri için de örneğin alındığı hastalığın evresi çok önemlidir. Antikor oluşumunun doğası gereği birinci haftadan sonra örneklerin uygun testlerle çalışılması gereklidir. Çapraz reaksiyonları engellemek için farklı antijenleri hedefleyen çeşitli testler kullanılabilir.
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