Sézary T-Cell Activating Factor Is aChlamydia pneumoniae-Associated Protein

Abstract

We previously identified a protein that was stimulatory for malignant Sézary T cells, termed Sézary T-cell activating factor (SAF). However, the identity of this protein has not been fully elucidated, nor has it’s role been determined in the pathogenesis of cutaneous T-cell lymphoma (CTCL). The basis for epidermotropism and proliferation of malignant cells in the skin of patients with CTCL is unknown. Using a monoclonal antibody inhibitory for SAF activity, we demonstrated that SAF is present in the skin of 16 of 27 samples from patients with mycosis fungoides, the predominant form of CTCL. In this report, the SAF determinant is demonstrated to be associated withChlamydia pneumoniae bacteria by immunohistochemistry, immunoelectron microscopy, and culture analysis. Reactivity of antibodies against an outer membrane protein of C. pneumoniae or against the lipopolysaccharide ofChlamydiae spp. demonstrated that these determinants are coexpressed in 90% of the SAF-positive samples. We confirmed the presence of C. pneumoniae DNA and RNA in the skin by PCR and reverse transcription-PCR and by sequence analysis of the PCR products. The expression of the C. pneumoniae antigens and SAF appears to be associated with active disease in that C. pneumoniae antigens were absent or greatly diminished in the skin of three patients examined after Psoralen and long-wave UVA radiation treatment. Our results suggest that SAF is aChlamydia-associated protein and that further investigation is warranted to determine whether SAF and C. pneumoniaeplay a role in the pathogenesis of CTCL.

Cutaneous malignant lymphomas: Update 2006

“…In Europa [19,20] , jedoch nicht in den USA [21], scheinen einige Fälle niedrigmaligner kutaner B-Zell-Lymphome (CBCL) mit Borrelia burgdorferi assoziiert zu sein. Der Sézary-T-Zell-aktivierende-Faktor (SAF) wurde als Chlamydien-assoziiertes Protein nachgewiesen, das möglicherweise eine Rolle in der Pathogenese der CTCL spielt, vor allem bei Formen mit Erythrodermie [22], ein Befund , der jedoch von anderen Arbeitsguppen nicht bestätigt werden konnte [23]. [26].…”

Association between Sézary T Cell‐activating Factor, Chlamydia pneumoniae, and Cutaneous T Cell Lymphoma

“…One of these antibody clones was found to inhibit PBMC and cell line-derived SAF while leaving PHA as well as PMA and ionomycin stimulation unaffected, supporting specificity in the inhibition. 19 This monoclonal antibody (mAb), as well as pools of inhibitory antibodies, was used in a series of screening procedures to identify a positive cDNA clone. The procedures included both blotting and bioassay expression systems.…”

“…23 Anti-SAF reactivity was tested on a section of brain tissue adjacent to another section confirmed to contain C. pneumoniae organisms and was found positive for SAF. 19 We then tested the staining pattern of anti-C. pneumoniae outer membrane protein (OMP) (FIG. 2B) and LPS (FIG.…”

“…Using the same primers on DNA isolated from skin samples of patients suffering from mycosis fungoides, we detected C. pneumoniae DNA in 5 of 5 samples tested. 19 Using a nested PCR primer pair, we amplified the appropriate-size PCR product using mRNA extracted from lymph nodes obtained from 3 of 5 patient samples. 19 All mRNA samples were subjected to DNase treatment prior to the addition of reverse transcriptase, and the no-reverse transcriptase controls were always negative.…”

“…19 Using a nested PCR primer pair, we amplified the appropriate-size PCR product using mRNA extracted from lymph nodes obtained from 3 of 5 patient samples. 19 All mRNA samples were subjected to DNase treatment prior to the addition of reverse transcriptase, and the no-reverse transcriptase controls were always negative. PCR products were sequenced and found to be identical (one base mismatch) to the TW-183 sequence.…”