Hepatitis C virus infection and kidney transplantation in 2014: what's new?

Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.

No evidence of skin infection with Chlamydia pneumoniae in patients with cutaneous T cell lymphoma.

Recently, Chlamydia pneumoniae-specific DNA and antigens were reported in the skin of patients with Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphomas. In order to revalidate these data we analyzed skin sections of patients with MF for the expression of three different chlamydial antigens and C. pneumoniae DNA by immunohistochemistry and PCR according to previously described protocolls. Neither C. pneumoniae-specific DNA sequences nor antigens were detected in any of the skin biopses from 24 MF patients tested, suggesting that further studies are needed to establish any pathogenetic relevance of C. pneumoniae in MF.

Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma? First experiences.

BACKGROUND: A standard therapy for advanced cutaneous T-cell lymphomas has not yet been defined. Bexarotene is a new retinoid x receptor-specific retinoid that has been approved for systemic second-line therapy for cutaneous T-cell lymphomas in the USA and Europe. In order to evaluate the efficacy of bexarotene in cutaneous T-cell lymphomas, a pilot trial was initiated. PATIENTS AND METHODS: In a pilot project 10 patients with advanced cutaneous T-cell lymphomas, who had received a variety of previous treatments, were treated with bexarotene at the departments of dermatology in Münster, Minden and Charité Berlin, Germany. The patients received bexarotene at a dose of 300 mg/m2 body surface daily. According to the percentage of tumour reduction and affected body surface, the response rates were divided in complete and partial remission, stable disease and progressive disease. Laboratory parameters i.e. cholesterol, triglycerides transaminases, T3, T4, and TSH were screened regularly. RESULTS: In 2 patients a short partial remission was achieved; however, after a few weeks progression followed. In 4 patients a lasting stabilisation was obtained. The other 4 patients showed a progressive disease during therapy. 6 patients developed hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in 3 patients because of these adverse drug events. CONCLUSION: Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.

Primary cutaneous follicle center cell lymphomas and large B cell lymphomas of the leg descend from germinal center cells. A single cell polymerase chain reaction analysis.

Primary cutaneous B cell lymphomas are defined as non-Hodgkin lymphomas that occur in the skin without extracutaneous involvement for 6 mo after diagnosis. They are characterized by a less aggressive course and better prognosis than their nodal counterparts. According to the European Organization for Research and Treatment of Cancer classification, the major subentities of primary cutaneous B cell lymphoma are follicle center cell lymphomas, immunocytomas, and large B cell lymphomas of the leg, which differ considerably regarding their clinical behavior, the former two being indolent, the latter being of intermediate malignancy. In this study, we applied a single cell polymerase chain reaction approach to analyze immunoglobulin V(H)/V(L) genes in 532 individual B lymphocytes from histologic sections of four follicle center cell lymphomas localized on the head and trunk, and four large B cell lymphomas on the leg. We found: (i) in six of eight patients a clonal heavy chain, and in seven of eight patients a clonal light chain rearrangement, all being potentially productive; (ii) no bias in VH gene usage, in four of seven light chain rearrangements the V kappa germline gene IGVK3-20*1 was used; (iii) no biallelic rearrangements; (iv) all V(H)/V(L) genes are extensively mutated (mutation rate 5.4-16.3%); (v) intraclonal diversity in six of eight cases (three of each group); and (vi) low replacement vs silent mutation ratios in framework regions indicating preservation of antigen-receptor structure, as in normal B cells selected for antibody expression. Our data indicate a germinal center cell origin of primary cutaneous follicle center cell lymphomas and large B cell lymphomas independent of those belonging to one of these subentities.

[Detection of monoclonal T-cells with TCR gamma PCR in mycosis fungoides]. / Nachweis von monoklonalen T-Zellen mittels TCR gamma-PCR bei Mycosis Fungoides (MF).

The monoclonal dominant malignant T cells in mycosis fungoides (MF) carry identical TCR gamma rearrangements. Their detection is a useful diagnostic tool. Thus, in routine diagnosis we investigated the occurrence of monoclonal T cells in skin biopsy samples of MF-patients by TCR gamma-PCR, followed by temperature gradient gel electrophoresis (TGGE). In 188 out of 208 MF patients, at least one skin sample with sufficient DNA quality for PCR analysis was obtained. Applying a consensus PCR for the TCR gamma genes V gamma I and J gamma 1/2, we detected monoclonal T cells in 122 cases (65%). In the remaining 66 cases, we performed two multiplex-PCRs, covering rearrangements of the other TCR gamma genes. Here we found in 11 cases (6%) predominant clonal rearrangements of V gamma II-IV and J gamma 1/2 and in 2 (1%) those of V gamma I-IV and J gamma P 1/2. In patients with MF, detecting rearrangements of only V gamma I and J gamma 1/2 is sufficient for PCR screening analysis. In 53 of the patients (28%) the applied methods revealed no monoclonal T cells. This may be due to a low cell number, oligoclonal nature, chromosomal abberations or remaining of TCR in germline configuration.

Hypocomplementaemic urticarial vasculitis: successful treatment with cyclophosphamide-dexamethasone pulse therapy.

Systemic hypocomplementaemic urticarial vasculitis unresponsive to several immunosuppressive and immunomodulatory drugs was seen in two women aged 43 and 45 years. Cyclophosphamide-dexamethasone pulse therapy was started in both patients and resulted in significant clinical improvement. The pulse treatment was well tolerated in both patients and no major adverse effects occurred. These cases indicate that cyclophosphamide-dexamethasone pulse therapy is efficient in the treatment of hypocomplementaemic urticarial vasculitis.

Nucleotide sequence comparison of the IgE constant region in patients with atopic dermatitis and non-atopic individuals.

In order to answer the question whether the Fc portion of the IgE molecule in patients with atopic dermatitis is altered by somatic replacement mutations, we amplified and sequenced the respective C epsilon 2 and C epsilon 3 domain genes. Five patients with atopic dermatitis and 6 non-atopic individuals were studied. Neither within the C epsilon 2 nor the C epsilon 3 domain could any common nucleotide substitutions be detected. Therefore, the conclusion can be drawn that, in patients with atopic dermatitis, there are no protein sequence differences within the Fc part of the IgE which could be responsible for distinct functional features with regard to Fc epsilon-receptor binding and signal transduction or could account for the frequent occurrence of anti-IgE autoantibodies in these individuals.