The discovery of a strong association between hepatitis C virus(HCV) infection and mixed cryoglobulinemia(MC) has led to an increasingly rare diagnosis of idiopathic essential MC(EMC).The incidence of EMC is high in r...The discovery of a strong association between hepatitis C virus(HCV) infection and mixed cryoglobulinemia(MC) has led to an increasingly rare diagnosis of idiopathic essential MC(EMC).The incidence of EMC is high in regions where there is a comparatively low HCV infection burden and low in areas of high infection prevalence,including HCV.The diagnosis of EMC requires an extensive laboratory investigation to exclude all possible causes of cryoglobulin formation.In addition,although cryoglobulin testing is simple,improper testing conditions will result in false negative results.Here,we present a 46-year-old female patient with a case of EMC with dermatological and renal manifestations,highlighting the importance of extensive investigation to reacha proper diagnosis.We review the need for appropriate laboratory testing,which is often neglected in clinical practice and which can result in false negative results.This review also emphasizes the significance of an extended testing repertoire necessary for better patient management.Despite a strong association of MC with HCV infection and other causes that lead to cryoglobulin formation,EMC remains a separate entity.Correct diagnosis requires proper temperature regulation during sample handling,as well as characterization and quantification of the cryoprecipitate.Inclusion of rheumatoid factor activity and complement levels in the cryoglobulin test-panel promotes better patient management and monitoring.Consensus guidelines should be developed and implemented for cryoglobulin detection and the diagnosis of cryoglobulinemic syndrome,which will reduce variability in inter-laboratory reporting.展开更多
Background: An accurate diagnosis of cause of acute renal graft dysfunction is crucial for the optimal management of transplant recipients. Currently available tests are either insensitive or nonspecific, or are invas...Background: An accurate diagnosis of cause of acute renal graft dysfunction is crucial for the optimal management of transplant recipients. Currently available tests are either insensitive or nonspecific, or are invasive, such as allograft biopsy. During last decade, attempts have been made in search of non invasive markers for the evaluation of cause of graft dysfunction. We studied a set of genes expressed on cytotoxic T Lymphocytes and those related to functioning of regulatory or helper T cells. Methods: We obtained 108 urine samples from 108 renal allograft recipients at the time of graft biopsy done for the evaluation of cause of graft dysfunction. RNA was extracted from urinary cells and messenger RNA (mRNA) encoding perforin, granzyme B (GB), FoxP3, CD3?, CXCR3, TGF-?, CTLA4, PI-9, IL-10, TNF?, T-bet and 18SrRNA measured with the use of quantitative real time polymerase chain reaction (RT-PCR). The levels of expression of genes were correlated with the biopsy findings and the results compared among different groups. Renal allograft biopsies at this institution are performed when there is unexplained rise in serum creatinine of >20% from the baseline value and reported according to Banff classification. SPSS v10.0 used for analy-sis.Results: The mRNA copy numbers of GB, Perforin, FoxP3, CD3, CXCR3, TGF-?, CTL A4, PI9, IL-10, TNF?, and T-bet were log transformed and mean (± SD) levels studied. The expression of all studied genes were compared between ‘nonspecific biopsy findings’ and other specific diagnoses. GB, Perforin, FoxP3, TGF-?, CD3?, CTLA4 CXCR3 and T-bet were higher in acute cellular rejection (ACR), whereas, TGF-? was also found higher in infection, and PI-9 in chronic allograft nephropathy (CAN) and borderline rejection group. Conclusion: Measurement of mRNA levels for genes like GB, Perforin, FoxP3, TGF-β, CD3?, CTLA4, CXCR3 and T-bet in urine samples offers a non invasive means of diag-nosing cause of graft dysfunction.展开更多
文摘The discovery of a strong association between hepatitis C virus(HCV) infection and mixed cryoglobulinemia(MC) has led to an increasingly rare diagnosis of idiopathic essential MC(EMC).The incidence of EMC is high in regions where there is a comparatively low HCV infection burden and low in areas of high infection prevalence,including HCV.The diagnosis of EMC requires an extensive laboratory investigation to exclude all possible causes of cryoglobulin formation.In addition,although cryoglobulin testing is simple,improper testing conditions will result in false negative results.Here,we present a 46-year-old female patient with a case of EMC with dermatological and renal manifestations,highlighting the importance of extensive investigation to reacha proper diagnosis.We review the need for appropriate laboratory testing,which is often neglected in clinical practice and which can result in false negative results.This review also emphasizes the significance of an extended testing repertoire necessary for better patient management.Despite a strong association of MC with HCV infection and other causes that lead to cryoglobulin formation,EMC remains a separate entity.Correct diagnosis requires proper temperature regulation during sample handling,as well as characterization and quantification of the cryoprecipitate.Inclusion of rheumatoid factor activity and complement levels in the cryoglobulin test-panel promotes better patient management and monitoring.Consensus guidelines should be developed and implemented for cryoglobulin detection and the diagnosis of cryoglobulinemic syndrome,which will reduce variability in inter-laboratory reporting.
文摘Background: An accurate diagnosis of cause of acute renal graft dysfunction is crucial for the optimal management of transplant recipients. Currently available tests are either insensitive or nonspecific, or are invasive, such as allograft biopsy. During last decade, attempts have been made in search of non invasive markers for the evaluation of cause of graft dysfunction. We studied a set of genes expressed on cytotoxic T Lymphocytes and those related to functioning of regulatory or helper T cells. Methods: We obtained 108 urine samples from 108 renal allograft recipients at the time of graft biopsy done for the evaluation of cause of graft dysfunction. RNA was extracted from urinary cells and messenger RNA (mRNA) encoding perforin, granzyme B (GB), FoxP3, CD3?, CXCR3, TGF-?, CTLA4, PI-9, IL-10, TNF?, T-bet and 18SrRNA measured with the use of quantitative real time polymerase chain reaction (RT-PCR). The levels of expression of genes were correlated with the biopsy findings and the results compared among different groups. Renal allograft biopsies at this institution are performed when there is unexplained rise in serum creatinine of >20% from the baseline value and reported according to Banff classification. SPSS v10.0 used for analy-sis.Results: The mRNA copy numbers of GB, Perforin, FoxP3, CD3, CXCR3, TGF-?, CTL A4, PI9, IL-10, TNF?, and T-bet were log transformed and mean (± SD) levels studied. The expression of all studied genes were compared between ‘nonspecific biopsy findings’ and other specific diagnoses. GB, Perforin, FoxP3, TGF-?, CD3?, CTLA4 CXCR3 and T-bet were higher in acute cellular rejection (ACR), whereas, TGF-? was also found higher in infection, and PI-9 in chronic allograft nephropathy (CAN) and borderline rejection group. Conclusion: Measurement of mRNA levels for genes like GB, Perforin, FoxP3, TGF-β, CD3?, CTLA4, CXCR3 and T-bet in urine samples offers a non invasive means of diag-nosing cause of graft dysfunction.
