• Wed. Feb 12th, 2025

Statistical analyses were performed using Stata 10

Byacusticavisual

Jan 28, 2025

Statistical analyses were performed using Stata 10.0 (Stata Corporation, College Station, TX, USA). polymerase I/III. In contrast, nucleolar RNA polymerase III staining was not detected in any of 4 examined tumors in the RNA polymerase antibody-negative group (p=0.048). Conclusions There is a close temporal relationship between onset of cancer and scleroderma in patients with antibodies to RNA polymerase I/III, which is usually distinct from scleroderma patients with other autoantibody specificities. In this study, autoantibody response and tumor antigen expression are associated. We propose that malignancy may initiate the scleroderma-specific immune response and drive disease in a subset of scleroderma patients. Introduction Patients with scleroderma may have an increased risk of malignancy compared to the general population (1C6). A wide array of cancers has been reported in scleroderma, although lung and breast cancers are thought to be the most common (3, 4, 6, 7). Although it is usually controversial whether malignancy risk is truly increased in scleroderma patients, reports detailing a close, PF-04449913 at times concurrent onset of scleroderma and malignancy raise the possibility of malignancy triggering an autoimmune disease process in PF-04449913 a subset of scleroderma patients (8C10). Among scleroderma patients, this tight temporal association is most striking in breast cancer, with the majority of cases developing scleroderma within 18 months of cancer diagnosis PITPNM1 (11C14). In 2 case series reviewing scleroderma patients with breast cancer, it has been estimated that up to 50% of breast cancer cases closely preceded or were diagnosed simultaneously with scleroderma (12, 14). Additionally, it is reported that prompt therapy of a malignancy can abrogate the scleroderma disease process (8, 9, 15), suggesting that in these unique cases the biological response to the malignancy or the malignant process itself may be driving the expression of scleroderma. Despite this reported association between malignancy and scleroderma onset, few studies have evaluated PF-04449913 scleroderma disease characteristics that associate with the presence or risk of malignancy, and little is known about potential mechanisms underlying this connection. We hypothesize that scleroderma-specific autoantibody production in a subset of patients with scleroderma is a manifestation of the immune response to tumor antigens that may associate with or induce the scleroderma disease process. In this study, we evaluated whether clinical characteristics, including the temporal relationship between scleroderma and malignancy onset, differed by autoantibody status among patients with scleroderma and cancer. After demonstrating a temporal clustering between cancer onset and scleroderma in the RNA polymerase antibody-positive group, we investigated the expression of RNA polymerases I and III in cancerous tissue of these scleroderma patients compared to cancers from RNA polymerase antibody-negative patients, as well as noncancerous tissue from controls. Patients and Methods Patients Participants were scleroderma patients followed at the Johns Hopkins Scleroderma Center who had (i) a new or past diagnosis of malignancy, (ii) an available serum sample, and (iii) an existing cancer pathology specimen available for histologic confirmation of cancer diagnosis. Among established patients, subjects were identified as having had a prior diagnosis of malignancy from the Centers research database. Eligibility included informed consent and meeting either American College of Rheumatology criteria for scleroderma (16), having at least 3 of 5 features of the CREST syndrome (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasias), or having definite Raynauds phenomenon, abnormal nailfold capillaries and the presence of a scleroderma-specific autoantibody. For all patients, the closest available serum sample to cancer diagnosis was studied. Demographic data, scleroderma subtype (limited versus diffuse skin disease), disease duration, date of cancer diagnosis, smoking status (never, former, or current), most recent Medsger disease severity scores (17), peak modified Rodnan skin scores (18), medication use prior to cancer diagnosis, autoantibody status, pulmonary function tests, and echocardiogram data were obtained from the Centers database and, when necessary, medical chart review. Patients were classified according to LeRoy et al (19) as having limited cutaneous disease if scleroderma skin changes were noted only on the face and/or distal to the knees and elbows; diffuse cutaneous disease involved the trunk and/or proximal extremities. Disease duration was defined as the period of time from the first non-Raynauds phenomenon symptom to the date of cancer diagnosis. Cancer onset was defined by the date of cancer diagnosis. All forced vital capacity (FVC) and diffusion capacity (DLCO) results were standardized by age, gender and.