Predominance of PR3 specific immune response and skewed TH17 vs. T-regulatory milieu in active granulomatosis with polyangiitis.

OBJECTIVE: We compared levels of Th1/Th2/Th17 cytokines and T-regulatory cells in active and remitting granulomatosis with polyangiitis (GPA). METHODOLOGY: Twenty-one cases of GPA in active state as well as in remitting state and 20 healthy controls (HC) were enrolled in the study. Cytokines were detected in culture supernatants of PBMCs after stimulation with proteinase-3 (PR3) and phytohemagglutinin antigen (PHA). Serum IL-17 cytokine was studied by ELISA. T-regulatory cells (Tregs) were analyzed by flow cytometry. Gene expression of FOXP3 and ROR-γt was compared by Real Time PCR. RESULTS: We observed significantly increased level of IL-17 in serum as well in culture supernatants of PBMCs after PR3 stimulation along with ROR-γt gene expression in active disease state of GPA as compared to HC. Importantly, remitting state showed low levels of serum IL-17 with decreased ROR-γt gene expression and increased FOXP3 expression. Using PR3 as an immunostimulant, we could demonstrate the generation of IL-17 and TNF-α secreting effector memory cells during remission. Reduced FOXP3 expression with reduced IL-10 levels in active disease indicated the reduced function of Tregs in active disease. CONCLUSION: We observed Th17 dominant environment in peripheral blood of patients in active state of disease, with "hyporesponsiveness", in, in vitro stimulated PBMC-in their ability to secrete TNF-α and IL-6. Treg numbers were unaltered but function was compromised. Targeting PR3 specific effector memory cells, to prevent relapse, and instituting anti IL-17 therapy, or modulating Tregs could be newer forms of therapy for this serious autoimmune disease.

Primary cutaneous aspergillosis: our experience in 10 years.

We describe nine patients with primary cutaneous aspergillosis who were diagnosed during the 10-year period between 1987 and 1996. All except one were adults. Seven of those nine cases had an immunocompromised state. Among the immunocompromised patients, six had burn wounds and one was a renal transplant recipient. Aspergillus flavus was isolated from seven patients and A. fumigatus from one, and in one other case the species could not be determined. Three patients who had total burn surface area of more than 70% died. The other patients responded well to extensive surgical debridement with or without institution of oral itraconazole.

Brain abscess in renal transplant recipients: report of three cases.

BACKGROUND: Neurologic complications occur in about 30% of renal transplant patients, infections being the most common. We encountered three such patients and present our experience in the management of such cases. CLINICAL MATERIAL: Three cases of brain abscess in renal transplant recipients are reported. These patients presented from 9-60 months after the transplant. One patient had a pyogenic abscess; in the second the organism identified was Nocardia asteroides; in the third, a fungal infection was responsible. In two patients excision of the abscess was done, while in one repeated aspirations with intracavitary antibiotics were used. All received systemic antimicrobial therapy. CONCLUSIONS: Central nervous system (CNS) complications, specifically infections, are quite common in renal transplant recipients, but reports of brain abscesses in these patients are very rare. The treatment options for such patients are discussed.

Therapeutic implication of quantitative pp65 antigen assay in living renal transplant in a high seroendemic population.

Various methods have been used to diagnose cytomegalovirus (CMV) infection/disease; however, pp65 antigenemia assay has emerged as a good marker for CMV disease in a high seroendemic population. We studied the role of quantitative pp65 antigen assay in live related renal transplant recipients in a high seroendemic population. Between November 1998 and May 2003, a total of 350 blood samples from 250 symptomatic patients were tested by quantitative pp65 antigen assay; 14% of the patients tested positive. There were 5 (14%) low-positive and 30 (86%) high-positive patients. All high-positive patients had CMV disease. The response to antiviral therapy monitored by the assay was dramatic, and one low-positive patient responded to reduction in immunosuppression. In conclusion, pp65 antigen assay is a good test for diagnosing CMV disease and monitoring response to antiviral therapy in a high seroendemic population.

Serial measurements of hepatitis C viral load by real-time polymerase chain reaction among recipients of living-donor renal transplants: a short-term follow-up study from a single center.

There is a high prevalence of hepatitis C virus (HCV) infection among immunosuppressed patients including renal transplant recipients. The study investigated serum viral loads for up to 6 months posttransplantation among these patients. Serum viral load was serially monitored using real-time polymerase chain reaction (PCR) in 25 HCV-positive renal transplant recipients pretransplantation as well as day 10 and 6 months posttransplantation. A liver biopsy specimen obtained under vision at the time of transplantation was analyzed for viral load as well as for histological changes. There was increased viremia at day 10 followed by a significant (2 log) reduction at 6 months posttransplantation. Pretransplantation serum and intrahepatic viral load showed significant positive correlations (r = 0.727; P = .001), the latter also reflecting liver fibrosis score (r = 0.423; P = .05). The findings suggested that serum viral load reflects intrahepatic viral load, which in turn correlates with liver fibrosis. At 6 months posttransplantation, the modulatory effects of immunosuppressive drugs and of the host immune response may lead to a reduced viral load.