Wegener's Granulomatosis: a Comprehensive Review

Wegener's Granulomatosis (WG) is a systemic multi-organ disease that is specifically characterised by inflammation of small and medium - sized vessels that could lead to tissue damage. Most commonly affected systems are the upper respiratory tract, the pulmonary, renal and ocular systems. Even though no diagnostic criteria have been established, the Chapel Hill Consensus definitions and the American College of Rheumatology classification criteria are widely used in clinical practice to identify WG. Definite diagnosis is confirmed by biopsy of the affected organ. This article reviews the epidemiology, pathophysiology, clinical manifestations, laboratory markers, diagnosis and disease assessment and, finally, the conventional and therapeutic options in WG

Microarray analysis of human leucocyte subsets: the advantages of positive selection and rapid purification.

BACKGROUND: For expression profiling to have a practical impact in the management of immune-related disease it is essential that it can be applied to peripheral blood cells. Early studies have used total peripheral blood mononuclear cells, and as a consequence the majority of the disease-related signatures identified have simply reflected differences in the relative abundance of individual cell types between patients and controls. To identify cell-specific changes in transcription it would be necessary to profile purified leucocyte subsets. RESULTS: We have used sequential rounds of positive selection to isolate CD4 and CD8 T cells, CD19 B cells, CD14 monocytes and CD16 neutrophils for microarray analysis from a single blood sample. We compared gene expression in cells isolated in parallel using either positive or negative selection and demonstrate that there are no significant consistent changes due to positive selection, and that the far inferior results obtained by negative selection are largely due to reduced purity. Finally, we demonstrate that storing cells prior to separation leads to profound changes in expression, predominantly in cells of the myeloid lineage. CONCLUSION: Leukocyte subsets should be prepared for microarray analysis by rapid positive selection.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.

Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity

Polyoma virus BK in renal transplant recipients and its role in chronic allograft dysfunction

Purpose: BK virus associated nephropathy (BKVAN) can be diagnosed only with renal graft biopsy. Definitive diagnosis of BKVAN requires demonstration of BKV replication in renal allograft tissues. Non-invasive analysis of urine and blood is considered essential in screening renal transplant recipients. Patients and methods: This study evaluated prospectively the replication of BKV in plasma and urine with qualitative and quantitative real-time polymerase chain reaction (PCR) in 32 de novo (group A) and 34 chronic (group B) renal transplant recipients and the long-term impact on graft function. Further the cytology method was evaluated in diagnosis of BKV replication in renal graft recipients and cytology results were correlated with polymerase chain reaction (PCR) in urine and plasma. Thin-prep methodology was used to prepare cytology slides. Results: In group A, 456 samples (228 plasma - 228 urine) were examined and BK virus was detected in 31 (31/228, 13.6%) samples of plasma and 57 (57/228, 25%) samples of urine in 20 (20/32, 62,5%) and 23 (23/32, 72%) recipients respectively. Incidence of viremia and viruria increased during the first six months presenting a peak the third post-operative month (viremia: 28% and viruria: 31%). Immune suppressive treatment with tacrolimus showed significant relation with viremia. Renal graft function in de novo renal transplant recipients remained stable throughout the follow-up period without influence of BK replication. In group B, incidence of viremia and viruria were 3% (1/34) and 9% (3/34) correspondingly, indicating that after the first post-transplant year the risk of BK virus re-activation is diminished. 190 urine samples were examined with cytology method. Decoy cells, indicative of BKV infection, were detected in 14 samples (14/190, 7.3%) which were derived from eleven recipients. In three cases with positive decoy cells, BK viremia and viruria were simultaneously identified. In a further three cases BKV active replication was confirmed in urine both with cytology and PCR. Conclusions: The highest incidence of BK viremia and viruria is observed the third post-transplantation month, confirming previously published studies in Europe and USA, and long-term follow up shows that BKV replication decreases significantly after the third post-transplant month and even transient viremia or viruria does not have an impact on renal function. Urine cytology is an easy and rapid method of detecting decoy cells in cases where renal biopsy is not possible. However, the low incidence of detection of decoy cells in the present study together with poor correlation with PCR results questions its sensitivity and specificity in diagnosing BKV reactivation.Σκοπός: Ο polyoma ιός ΒΚ έχει ενοχοποιηθεί για την πρόκληση διάμεσης νεφρίτιδας στο νεφρικό μόσχευμα που δυνητικά οδηγεί σε έκπτωση της νεφρικής λειτουργίας και απώλεια του μοσχεύματος. Ασθενείς - Μεθοδολογία: Στην παρούσα προοπτική μελετήθηκε ο ιός ΒΚ σε 32 νέους λήπτες νεφρικού μοσχεύματος, από την πρώτη μετεγχειρητική ημέρα μέχρι και 18 μήνες μετά τη μεταμόσχευση, 34 χρόνιους λήπτες νεφρικού μοσχεύματος και 30 υγιείς ενήλικες. Χρησιμοποιήθηκε η μεθοδολογία της αλυσιδωτής αντίδρασης πολυμεράσης πραγματικού χρόνου (real-time polymerase chain reaction) για την ανίχνευση του ιού ΒΚ και την ποσοτικοποίηση του ιικού φορτίου σε δείγματα πλάσματος και ούρων καθώς και η μέθοδος της κυτταρολογίας για τον εντοπισμό χαρακτηριστικών κυττάρων «εν είδη δολώματος» (decoy cells) σε δείγματα ούρων. Αποτελέσματα: Στην ομάδα των νέων ληπτών νεφρικού μοσχεύματος με τη μέθοδο της PCR εξετάσθηκαν συνολικά 456 δείγματα (228 δείγματα αίματος και 228 δείγματα ούρων) και ανιχνεύθηκαν 31 θετικά δείγματα για τον ιό ΒΚ στο πλάσμα, ποσοστό 13,6% επί του συνόλου των δειγμάτων (31/228, 13,6%) και 57 θετικά δείγματα για τον ιό ΒΚ στα ούρα, που αντιστοιχούν σε ποσοστό 25% των εξετασθέντων δειγμάτων (57/228, 25%). Σημειώθηκε αύξηση τόσο της ιαιμίας όσο και της ιουρίας κατά τη διάρκεια των πρώτων έξι μηνών μετά τη μεταμόσχευση νεφρού με χαρακτηριστική κορυφή τον τρίτο μετεγχειρητικό μήνα. Η λειτουργία του νεφρικού μοσχεύματος παρέμεινε σταθερή κατά την περίοδο παρακολούθησης χωρίς να παρατηρηθεί ότι ο πολλαπλασιασμός του ιού επηρεάζει τη νεφρική λειτουργία. Από την ανάλυση των αποτελεσμάτων διαπιστώθηκε ότι οι λήπτες νεφρικού μοσχεύματος που ελάμβαναν ανοσοκαταστολή με tacrolimus είχαν υψηλότερο ποσοστό επίπτωσης ΒΚ ιαιμίας και ιουρίας συγκριτικά με αυτούς που ελάμβαναν σχήμα με κύριο ανοσοκατασταλτικό την κυκλοσπορίνη. Στην ομάδα των παλαιών μεταμοσχευμένων ασθενών η επίπτωση της ιαιμίας και της ιουρία ήταν αντιστοίχως 3% (1/34) and 9% (3/34), γεγονός που υποδηλώνει ότι μεγαλύτερος κίνδυνος ενεργοποίησης του ιού παρατηρείται κατά τη διάρκεια του πρώτου έτους. Από τον έλεγχο των υγιών ενηλίκων δεν παρατηρήθηκαν θετικά δείγματα για τον ιό ΒΚ. Με τη μέθοδο της κυτταρολογίας εξετάσθηκαν 190 δείγματα ούρων που ελήφθησαν από νέους λήπτες νεφρικού μοσχεύματος. Χαρακτηριστικά κύτταρα decoy εντοπίσθηκαν σε 14 δείγματα ούρων (14/190, 7,3%), τα οποία προέρχονταν από 11 λήπτες. Συμπέρασμα: Συμπερασματικά, τα υψηλά ποσοστά πολλαπλασιασμού του ιού ΒΚ μετά από μεταμόσχευση νεφρού υποδηλώνουν ότι ο ιός ενεργοποιείται χωρίς απαραίτητα να επηρεάζεται η νεφρική λειτουργία. Η χαμηλή επίπτωση ανίχνευσης κυττάρων decoy στα ούρα συγκρινόμενη με τη μέθοδο της PCR συντείνουν ότι μοριακή μέθοδος είναι πιο ευαίσθητη μέθοδος για την ανίχνευση του ιικού γενετικού υλικού συγκριτικά με τον εντοπισμό προσβεβλημένων κυττάρων στο απλό μικροσκόπιο

Fournier′s gangrene due to perioperative iatrogenic colon perforation in a renal transplant recipient

Fournier′s gangrene is not a common cause of morbidity in renal transplant recipients, but, if it occurs, it is difficult to treat because of the immunosuppression and associated increased mortality rate. We describe the case of a male patient who underwent renal transplantation with complicated post-operative course, resulting in cecum perforation (thermal injury due to cautery use during transplantation) requiring exploratory laparotomy and cecostomy. A few days later, he developed Fournier′s gangrene and urgent radical surgical debridement of the scrotum was performed, along with aggressive antibiotic regimen and the immunosuppressive treatment was modified. Subsequently, the patient underwent scheduled cecostomy closure (right hemicolectomy), while the scrotum trauma healed with tertiary intention. Epidemiologic characteristics, clinical presentation, diagnostic workup, therapeutic options and morbidity-mortality rates of Fournier′s gangrene are reviewed, emphasizing the role of immunosuppression in renal transplant recipients to disease development

Increased Prevalence and Severity of Coronary Artery Calcification in Patients with Chronic Kidney Disease Stage III and IV

Background: Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). The pathophysiology of coronary artery disease in CKD is multifactorial including, in addition to traditional risk factors (hypertension, hyperlipidemia, diabetes mellitus), parameters related to uremia. Methods: The study consisted of measuring coronary artery calcification (CAC) score in patients with CKD stage III and IV without history of CVD and in a group of controls with normal renal function matched for age, gender and risk factors using multi-detector computed tomography. Results: The study included 49 patients and 49 controls. CAC was present in 79.6% in the CKD group versus 59.2% in the control group (p = 0.028). The median CAC score value in CKD patients was 139 (interquartile range (IQR): 23–321) versus 61 (IQR: 6–205) in controls (p = 0.007). CAC was associated with traditional risk factors such as older age, hypertension and baseline cardiovascular risk score, while CKD patients with severe calcification had marginally lower estimated glomerular filtration rate and increased levels of parathormone. Conclusions: CAC is more frequent and severe in patients with CKD stage III and IV compared to matched controls with normal renal function, even though kidney disease-related parameters are not directly correlated with intensity of calcification

Neutrophil Gelatinase-Associated Lipocalin as a Biomarker of Acute Kidney Injury in Patients with Morbid Obesity Who Underwent Bariatric Surgery

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a biomarker of acute kidney injury (AKI) that could contribute to early diagnosis and effective management of AKI. The purpose of this study was to evaluate NGAL as a predictive marker of AKI in patients with clinically severe obesity (BMI >50) who underwent biliopancreatic diversion surgery. Patients and Methods: We prospectively studied 23 patients with clinically severe obesity who underwent biliopancreatic bypass surgery. NGAL was measured using chemiluminescent microparticle immunoassay in three urine samples collected from each patient before surgery (first sample), 2-6 h after surgery (second sample) and on the first postoperative day (third sample). Results: Renal function was evaluated using serum creatinine values, which were 0.91 ± 0.26 mg/dl before surgery, 0.87 ± 0.31 mg/dl immediately after surgery and 0.92 ± 0.62 mg/dl on the fifth postoperative day. During the immediate postoperative period, AKI was observed in 2 patients, one of whom required renal replacement therapy with hemodialysis. In both patients, urine NGAL increased within the first postoperative hours before the values of serum creatinine increased. Conclusion: Urine NGAL in patients with clinically severe obesity, which was surgically treated, might be a potential biomarker of early AKI detection. Further research is required in order to confirm these results observed in a small number of patients who developed postoperative AKI and make recommendations for predictive NGAL values in patients who underwent bariatric surgery

Fulminant pancytopenia due to cytomegalovirus infection in an immunocompetent adult

AbstractA case of severe and irreversible pancytopenia secondary to acute primary cytomegalovirus infection in an immunocompetent woman is described. The patient presented with thrombocytopenia, lymphopenia, anemia, and abnormal liver function tests. Treatment with corticosteroids and intravenous immunoglobulin was ineffective in reconstituting hemopoiesis. The patient developed severe sepsis and eventually expired

A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.

Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity