Presence of Chlamydophila pneumoniae DNA in blood cells is a frequent event in patients with the late stage of primary cutaneous lymphomas and with atopic dermatitis

Introduction: Microbial infection and associated super antigens have been implicated in the pathogenesis of cutaneous T-cell lymphoma (CTCL), and many patients die from complicating bacterial infections. It has been postulated that Chlamydophila pneumoniae (C. pneumoniae) infection may be involved in the pathogenesis of Mycosis fungoides (MF) but published data are limited and controversial. Aim: To analyze the frequency of (C. pneumoniae) DNA presence in blood samples of lymphoma cases. Material and methods: Using Q-PCR method we analyzed the presence of DNA in the blood samples obtained from 57 patients with CTCL (55 - mycosis fungoides (MF)/Sezary syndrome (SS), one primary cutaneous anaplastic large cell lymphoma (CD30+) and one NKT cell lymphoma) and 3 patients with cutaneous B-cell lymphomas, and 120 individuals from control groups (40 patients with psoriasis, 40 patients with atopic dermatitis and 40 healthy controls). Results: Chlamydophila pneumoniae DNA was identified in 13 of 55 cases in the MF/SS group (23.6%), in 1 patient with CD30+ large cell lymphoma and in 1 of 3 patients with B-cell lymphoma. The presence of C. pneumoniae was confirmed in 1 of 40 psoriatic patients (2.5%), in 5 of 40 patients with atopic dermatitis (12.5%) and in none of 40 healthy individuals. Presence of C. pneumoniae DNA in MF patients was strongly associated with disease progression; rs = 0.756; p = 0.0123 for groups IA -> IVB, and was noted more frequently in advanced (III + IV) stages than in early (I-II) stages (p = 0.0139). There are no differences in the mean age of MF/SS patients with and without infection. Conclusions: The presence of C. pneumoniae DNA in the blood cells is a frequent event in late stages of MF/SS and may be explained by Th2 shift and suppression of the immune system during the course of the disease.Peer reviewe

Expression of Human Endogenous Retrovirus-W Including Syncytin-1 in Cutaneous T-Cell Lymphoma

Peer reviewe

Chromosomally Clonal T Cells in the Skin, Blood, or Lymph Nodes of Two Sezary Syndrome Patients Express CD45RA, CD45RO, CDw150, and Interleukin-4, but no Interleukin-2 or Interferon-γ

Cutaneous T cell lymphomas are considered to represent a clonal malignancy of mature T lymphocytes of the T helper memory subtype. A method enabling the direct identification of clonal malignant cells in tissue and, at the same time, identification of the surface molecules they express has not been available, however. We have developed an application of the FICTION technique (simultaneous fluorescence immunophenotyping and interphase cytogenetics) to be used on fresh blood, skin, and lymph node samples. A prerequisite for this method is the characterization of a moleculocytogenetic clone in order to select the proper probes. With this method, we demonstrate that the true malignant cells express CD3, CD4, and CD45RO in the blood, skin, and lymph nodes of two Sezary syndrome patients. The majority of these cells express also CD45RA (albeit of varying intensity) and CDw150. The cytokine expression pattern of the clonal cells in skin and lymph nodes was interleukin-2 and interferon-γ negative and interleukin-4 positive. Interleukin-10 expression varied. The malignant cells did not express granzyme B, thus indicating that they do not have cytotoxic properties. Clonal cells with the same constant phenotype could be found even in lymph nodes with not yet morphologically identifiable malignant cells. This is the first report of the FICTION method applied directly on skin tissue. With this method we demonstrated that the chromosomally clonal cells in these two cases of Sezary syndrome could be intermediate forms between naïve CD45RA+ and CD45RO+ Th2 cells

Clinicopathological Characterization and Genomic Aberrations in Subcutaneous Panniculitis-Like T-Cell Lymphoma

Subcutaneous panniculitis-like T-cell lymphomas (SPTLs) represent a rare, difficult-to-diagnose, and poorly characterized subtype of cutaneous T-cell lymphomas (CTCLs) affecting younger people more than the other CTCL forms. We performed a thorough clinical, immunohistological, and molecular analysis of nine Finnish SPTL patients. Specifically, we performed single-cell comparative genomic hybridization (CGH) from laser microdissected, morphologically malignant SPTL cells, as well as loss of heterozygosity (LOH) and fluorescence in situ hybridization (FISH) analysis for the NAV3 (neuron navigator 3) gene. CGH revealed large numbers of DNA copy number changes, the most common of which were losses of chromosomes 1pter, 2pter, 10qter, 11qter, 12qter, 16, 19, 20, and 22 and gains of chromosomes 2q and 4q. Some of the DNA copy number aberrations in SPTL, such as loss of 10q, 17p, and chromosome 19, overlap with those characteristic of common forms of CTCL (mycosis fungoides (MF) and Sezary syndrome (SS)), whereas 5q and 13q gains characterize SPTL. Allelic NAV3 aberrations (LOH or deletion by FISH), previously found in MF and SS, were identified in 44% of the SPTL samples. This study demonstrates that SPTL is also moleculocytogenetically a uniform entity of CTCL and supports the current World Health Organization–European Organization for Research and Treatment of Cancer (WHO–EORTC) classification defining SPTL as a subgroup of its own

Relative quantification of specific HERV-W transcript levels.

<p>Lesion (A) and non-malignant (B) cDNAs from each patient (patients 1-8, 12, representing stages III, IA, IVA, fMF, fMF, IB, IA, IB, IB, in respective order) were amplified using HERV-W specific primers (targeting a region within the <i>pol</i> gene) and normalized with housekeeping gene RNA polymerase II. Lesion samples are depicted by dark grey bars, non-malignant intact skin samples by light gray bars. No data in patient1B and patient 2B means there was no detectable transcription. Relative mRNA expression levels are given as mean ±SD. Statistical significance is presented as *p<0.05, **p>0.02, and ***p<0.01. Concordance between the microarray and qRT-PCR data is not complete due to the differences in primer specificities (see Methods). fMF= folliculotrophic MF.</p