Mutations affecting the actin regulator WD repeat–containing protein 1 lead to aberrant lymphoid immunity

Background: The actin-interacting protein WD repeat–containing protein 1 (WDR1) promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have been identified recently in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells. Objective: Given the pleiotropic expression of WDR1, here we investigated to what extent it might control the lymphoid arm of the immune system in human subjects. Methods: Histologic and detailed immunologic analyses were performed to elucidate the role of WDR1 in the development and function of B and T lymphocytes. Results: Here we identified novel homozygous and compound heterozygous WDR1 missense mutations in 6 patients belonging to 3 kindreds who presented with respiratory tract infections, skin ulceration, and stomatitis. In addition to defective adhesion and motility of neutrophils and monocytes, WDR1 deficiency was associated with aberrant T-cell activation and B-cell development. T lymphocytes appeared to develop normally in the patients, except for the follicular helper T-cell subset. However, peripheral T cells from the patients accumulated atypical actin structures at the immunologic synapse and displayed reduced calcium flux and mildly impaired proliferation on T-cell receptor stimulation. WDR1 deficiency was associated with even more severe abnormalities of the B-cell compartment, including peripheral B-cell lymphopenia, paucity of B-cell progenitors in the bone marrow, lack of switched memory B cells, reduced clonal diversity, abnormal B-cell spreading, and increased apoptosis on B-cell receptor/Toll-like receptor stimulation. Conclusion: Our study identifies a novel role for WDR1 in adaptive immunity, highlighting WDR1 as a central regulator of actin turnover during formation of the B-cell and T-cell immunologic synapses

Konjenital akral melanositik nevüslerin dermoskopik özelliklerinin edinsel akral melanositik nevüsler ile karşılaştırılması

Bu tezin, veri tabanı üzerinden yayınlanma izni bulunmamaktadır. Yayınlanma izni olmayan tezlerin basılı kopyalarına Üniversite kütüphaneniz aracılığıyla (TÜBESS üzerinden) erişebilirsiniz.[Abstarct Not Available

Pityriasis Lichenoides et Varioliformis Acuta Due to Infection: A Case Report

A nine-year old girl admitted to our clinic with two months history of itchy skin eruption, initially started on the arms and then disseminated to all the body including the face. Dermatological examination revealed extensive papulosquamous lesions covered with hemorrhagic crust and central necrosis. Clinically the diagnosis was thought to be pityriasis lichenoides et varioliformis acuta (PLEVA) and a skin biopsy was performed from a lesion which revealed exocytosis and spongiosis in epidermis, edema and exocytosis of erythrocytes in papillary dermis, perivascular lymphocytic infiltration in dermis. In laboratory evaluation, oropharyngeal culture was positive for Streptococcus pyogenes. The analysis of urine sample revealed leucocyturia and Escherichia coli grew on urine culture. Therapy with erythromycin, which was found to be sensitive against both pathogens, and also the main therapeutic agent for PLEVA started 250mg tb 4x1 orally, since the histopathological findings were also compatible with PLEVA. A rapid response was achieved and more than half of the lesions were found to be regressed in ten days. In this report, a child of PLEVA with a rapid and dramatic response to erythromycin therapy is described with a brief literature review

POEMS sendromu: Olgu sunumu

Presented with characteristic polyneuropathy and multisystemic manifestations, POEMS syndrome is a rare plasma cell disorder. Vascular endothelial growth factor, secreted by plasmacytoma, is considered responsible for these symptoms. The first symptoms in this patient were arthralgia, distal sensory impairment ascending proximally and motor impairment of distal lower extremities. By immunoelectrophoresis, M protein in serum and urine was detected. In addition to polyneuropathy and monoclonal gammopathy, the patient presented with organomegaly, endocrine dysfunction and skin changes, and was diagnosed as POEMS syndrome. This rare syndrome should be included in the differential diagnosis of acquired neuropathies associated with multisystemic manifestations.POEMS sendromu, polinöropati ve multisistemik tutulum ile seyreden oldukça ender görülen bir plazma hücre diskrazisidir. Semptomlardan plazmasitom tarafından salgılanan vasküler endotelyal büyüme faktörü sorumlu tutulmaktadır. Distal simetrik sensörimotor polinöropati kliniği ile başvuran, yanı sıra organomegali, endokrin bozukluk ve deri değişiklikleri de olan olgunun immünelektroforezinde serum ve idrarda M proteini saptanması nedeniyle POEMS sendromu düşünülmüştür. Edinsel nöropatilerin ayırıcı tanısında akla gelmesi gereken bu sendrom ender görülmesi nedeniyle sunulmuştur