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Background: The presence of antibodies to CTLA-4, a negative regulator of T-cell activation, was investigated in multiply transfused patients with malignant and non- malignant hematologic diseases. A previous study showed that, in multiply transfused patients, an immune response against nuclear matrix proteins can be induced by WBCs undergoing apoptosis during RBC unit storage. This study evaluated whether the same phenomenon could be involved in the induction of CTLA-4 antibodies in the patients analyzed.Study Design and Methods: Patient sera were tested for binding to the recombinant full-length CTLA-4 beta-galactosidase fusion protein by an ELISA. Immuno-fluorescence stainings were performed to analyze the CTLA-4 epitopes recognized by the antibodies and to detect such epitopes in the apoptotic cells present in the RBC units.Results: CTLA-4 antibodies were found in multiply transfused patients with beta-thalassemia (40%) and with other hemolytic diseases (33%) including leukemias (42%). A higher incidence of CTLA-4 antibodies was found in patients receiving non-WBC-reduced blood (88%) than in those receiving WBC-reduced blood (26%). Immunofluorescence staining showed that WBCs undergoing apoptosis in the RBC unit expressed CTLA-4 epitopes.Conclusions: The apoptotic WBCs present in the RBC units, after cold storage, express CTLA-4 epitopes. These epitopes can be released and induce formation of CTLA-4 antibodies with profound implications in the development of autoimmune disorders and in facilitating tumor dissemination and metastasis. [ABSTRACT FROM AUTHOR]

A letter to the editor about a case of inherited myotonic muscular dystrophy is presented.

Background: The widespread use of ultrasonography has led to an increased number of incidentally detected small non-palpable lesions, with Leydig cell tumours representing the majority of them., Objectives: The ultrasonography, real-time elastography and contrast-enhanced ultrasonography features of a large series of non-palpable testicular lesions were evaluated, focusing on the differences between Leydig cell tumours and other testicular masses., Materials and Methods: Of the 4679 testicular ultrasonography examinations performed at the Authors' Institution between January 2009 and December 2018, 78 patients (1.7%) were incidentally diagnosed with at least one non-palpable lesion and were enrolled. Thirteen patients (16.6%) declined surgery and were thus excluded. The remaining 65 underwent surgical resection with frozen section analysis. The conventional ultrasonography, colour Doppler, real-time elastography and contrast-enhanced ultrasonography were performed by a radiologist having more than 10 years of experience. Demographic and clinical data were collected., Results: Leydig cell tumours were detected in 32 patients, being the most frequent benign tumours (49.2%); of the non-Leydig cell tumours, 25 patients had malignant tumours, five non-neoplastic lesions and three other benign tumours. The Leydig cell tumour group had mostly infertility problems whereas the non-Leydig cell tumour group frequently experienced pain (p < 0.001). Leydig cell tumours were all hypoechoic (32/32, 100%; p = 0.002), more frequently presented with well-defined margins compared to non-Leydig cell tumours (30/32, 93.8% vs. 19/33, 57.6%; p = 0.001) and tended to be smaller than non-Leydig cell tumours (5.3 mm [standard deviation 2.7 mm] vs. 10.6 mm [standard deviation 3.8 mm], respectively; p < 0.001). The vascular pattern characterised by the rapid wash-in followed by the delayed wash-out observed during contrast-enhanced ultrasonography was significantly associated with the Leydig cell tumour histological diagnosis, even at multivariate analysis (odds ratio 480.5, p < 0.001), and yielded a high diagnostic accuracy (area under the receiver operating characteristic curve 0.954, 95% confidence interval 0.903-1)., Discussion: Contrast-enhanced ultrasonography demonstrated high diagnostic accuracy in identifying benign testicular lesions, such as Leydig cell tumours; they are the most common non-palpable tumours detected in infertile men and may benefit from enucleation., (© 2022 American Society of Andrology and European Academy of Andrology.)