ABSTRACT
OBJECTIVES: To characterize the splicing machinery (SM) of leukocytes from primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome with lupus (APS + SLE) patients, and to assess its clinical involvement. METHODS: Monocytes, lymphocytes and neutrophils from 80 patients (22 APS, 35 SLE and 23 APS + SLE) and 50 HD were purified, and 45 selected SM components were evaluated by qPCR-microfluidic array. Relationship with clinical features and underlying regulatory mechanisms were assessed. RESULTS: APS, SLE and APS + SLE leukocytes displayed significant and specific alterations in SM-components (SMC), associated with clinical features [autoimmune profiles, disease activity, lupus nephritis (LN), and CV-risk markers]. A remarkable relationship among dysregulated SMC in monocytes and the presence of LN in SLE was highlighted, revealing a novel pathological mechanism, which was further explored. Immunohistology analysis of renal biopsies highlighted the pathological role of the myeloid compartment in LN. Transcriptomic analysis of monocytes from SLE-LN(+) vs SLE-LN(-) identified 271 genes differentially expressed, mainly involved in inflammation and IFN-signaling. Levels of IFN-related genes correlated with those of SMC in SLE-LN(+). These results were validated in two external SLE-LN(+) datasets of whole-blood and kidney biopsies. In vitro, SLE-LN(+)-serum promoted a concomitant dysregulation of both, the IFN signature and several SMC, further reversed by JAKinibs treatment. Interestingly, IFNs, key inflammatory cytokines in SLE pathology, also altered SMC. Lastly, the over/down-expression of selected SMC in SLE-monocytes reduced the release of inflammatory cytokines and their adhesion capacity. CONCLUSION: Overall, we have identified, for the first time, a specific alteration of SMC in leukocytes from APS, SLE and APS + SLE patients that would be responsible for the development of distinctive clinical profiles.
Subject(s)
Antiphospholipid Syndrome , Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Inflammation , CytokinesABSTRACT
El tumor miofibroblástico inflamatorio es un tumor raro. Su localización más habitual es el pulmón. Se han descrito otras localizaciones extrapulmonares, siendo el mesenterio y el retroperitoneo las más frecuentes. Presentamos un caso de una niña de 8 años con un tumor miofibroblástico inflamatorio en una localización inusual. La paciente fue derivada a nuestro centro por sospecha de un proceso apendicular complicado. Se realizó una ecografía abdominal en la que se detectó una invaginación de íleon terminal, con una tumoración en su extremo distal. En la intervención urgente se confirmó una invaginación de íleon distal, secundaria a una tumoración intraluminal. El resultado anatomopatológico final fue de tumor miofibroblástico inflamatorio. El tumor miofibroblástico inflamatorio es un tumor mesenquimal raro, que afecta con mayor frecuencia a niños. Cuando se localiza en el abdomen, puede simular lesiones malignas, como linfoma, sarcoma o metástasis. Su etiología y pronóstico son inciertos (AU)
Inflammatory myofibroblastic tumor is a rare lesion that is usually located in the lung. The most commonly reported extrapulmonary locations are the mesentery and the retroperitoneum. We report the case of an 8-year-old girl with an inflammatory myofibroblastic tumor in an unusual location. The patient was referred to our center for suspected complicated appendicitis. Abdominal ultrasonography detected ileoileal intussusception with a mass in the distal portion. Emergency laparotomy confirmed ileoileal intussusception secondary to an intraluminal tumor. Histologic study revealed the mass was an inflammatory myofibroblastic tumor. Inflammatory myofibroblastic tumors are rare mesenchymal masses usually found in children. When located in the abdomen, they can mimic malignant lesions like lymphomas, sarcomas, or metastases. The cause and prognosis of inflammatory myofibroblastic tumors are unknown (AU)
Subject(s)
Humans , Female , Child , Intussusception/complications , Intussusception/diagnosis , Neoplasms, Muscle Tissue/complications , Neoplasms, Muscle Tissue/diagnosis , Intestinal Obstruction/complications , Intestinal Obstruction , Immunohistochemistry/methods , Intussusception/physiopathology , Intussusception , Neoplasms, Muscle Tissue , Abdomen , Anastomosis, Surgical/methodsABSTRACT
Inflammatory myofibroblastic tumor is a rare lesion that is usually located in the lung. The most commonly reported extrapulmonary locations are the mesentery and the retroperitoneum. We report the case of an 8-year-old girl with an inflammatory myofibroblastic tumor in an unusual location. The patient was referred to our center for suspected complicated appendicitis. Abdominal ultrasonography detected ileoileal intussusception with a mass in the distal portion. Emergency laparotomy confirmed ileoileal intussusception secondary to an intraluminal tumor. Histologic study revealed the mass was an inflammatory myofibroblastic tumor. Inflammatory myofibroblastic tumors are rare mesenchymal masses usually found in children. When located in the abdomen, they can mimic malignant lesions like lymphomas, sarcomas, or metastases. The cause and prognosis of inflammatory myofibroblastic tumors are unknown.
