BackgroundOsteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography.ResultsWe identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples.ConclusionsWe present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis.
BackgroundRheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis.ResultsWe have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ≥3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis.ConclusionsWe report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis.Sartaj Ahmad and Raja Sekhar Nirujogi contributed equally to this article.
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a drug reaction commonly occurring in association with aromatic anticonvulsants and allopurinol. It is characterized by triad of fever, skin eruption, and systemic involvement. DRESS is rare with beta-lactam antibiotics and even rarer with ceftriaxone. We describe a case of pneumonia who developed ceftriaxone-induced rash, bicytopenia, eosinophilia, transaminitis and was eventually diagnosed and managed successfully as a case of DRESS.
Background:Infectious disorders are a major cause of concern in renal transplant recipients (RTRs) leading to considerable morbidity and mortality. We studied the profile and outcomes of infectious disorders in a cohort of RTR.Materials and Methods:In this prospective, observational study, we evaluated all RTR who presented with the features of infection. We also included asymptomatic patients with microbiological evidence of infection. We excluded patients with acute rejection, drug toxicity, and malignancy. Descriptive statistics were used to analyze the results.Results:The study population (n = 45, 35 male and 10 female) had a mean age of 35.5 ± 10.4 years and follow-up after transplant was 2.1 ± 1.7 years. Urinary tract infection (UTI, n = 15) is the most common infection followed by tuberculosis (TB, n = 8), cytomegalovirus (n = 6), candidiasis (n = 7), and hepatitis (n = 11). Miscellaneous infections such as cryptosporidiosis and pneumocystis were seen in 10 patients. Simultaneous infections with two organisms were seen in 7 patients. Four patients succumbed to multiorgan dysfunction following sepsis, another 4 patients developed chronic graft dysfunction, while the remaining 35 RTR had a good graft function.Conclusion:Infectious complications are very common in the posttransplant period including UTI and TB. Further large scale studies are required to identify the potential risk factors leading to infections in RTR.
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