Impact of peripheral immune status on central molecular responses to facial nerve axotomy.

When facial nerve axotomy (FNA) is performed on immunodeficient recombinase activating gene-2 knockout (RAG-2-/-) mice, there is greater facial motoneuron (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2-/- mice with whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS). Immunoreconstitution of RAG-2-/- mice with lymphocytes from the mutant superoxide dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA. The objective of the current study was to characterize the effect of CD4+ T cells on the central molecular response to FNA and then identify if mSOD1 whole splenocytes blocked these regulatory pathways. Gene expression profiles of the axotomized facial motor nucleus were assessed from RAG-2-/- mice immunoreconstituted with either CD4+ T cells or whole splenocytes from WT or mSOD1 donors. The findings indicate that immunodeficient mice have suppressed glial activation after axotomy, and cell transfer of WT CD4+ T cells rescues microenvironment responses. Additionally, mSOD1 whole splenocyte recipients exhibit an increased astrocyte activation response to FNA. In RAG-2-/- + mSOD1 whole splenocyte mice, an elevation of motoneuron-specific Fas cell death pathways is also observed. Altogether, these findings suggest that mSOD1 whole splenocytes do not suppress mSOD1 CD4+ T cell regulation of the microenvironment, and instead, mSOD1 whole splenocytes may promote motoneuron death by either promoting a neurotoxic astrocyte phenotype or inducing Fas-mediated cell death pathways. This study demonstrates that peripheral immune status significantly affects central responses to nerve injury. Future studies will elucidate the mechanisms by which mSOD1 whole splenocytes promote cell death and if inhibiting this mechanism can preserve motoneuron survival in injury and disease.

[Disseminated perinaevic Meyerson phenomenon revealing melanoma]. / Phénomène de Meyerson périnævique disséminé révélateur d'un mélanome.

BACKGROUND: Meyerson phenomenon (MP) consists of an eczematous reaction occurring around a pre-existing dermatologic lesion that is usually melanocytic and generally benign, and which is known as a Meyerson naevus. We report a case of multiple Meyerson naevi revealing melanoma, which itself was surrounded by a halo of eczema. PATIENTS AND METHODS: A 55-year-old man of phototype III with atopic eczema presented for pruritic eczema present for a fortnight, found solely on and around the naevi on his trunk and at roots of his limbs. One of the melanocytic lesions affected by these Meyerson phenomena was clinically atypical and had been active for several years. Excision confirmed the diagnosis of level II extensive superficial melanoma measuring 0.75 mm in thickness and associated with lesional and perilesional eczematous remodelling. After surgery involving a 1-cm excision margin and local corticosteroid therapy of the eczema, the Meyerson phenomenon subsided with complete remission of the melanoma at 1 year. DISCUSSION: Meyerson phenomenon can affect one or more naevi at the same time; it is generally transient, may recur on occasion, and has a favourable outcome either spontaneously or with corticosteroid treatment. When not removed for histological verification, the melanocytic lesion regains its initial appearance following resolution of the phenomenon. MP differs from Sutton phenomenon (SP), which is a perinaevic vitiligo reaction leading to complete or partial regression of the melanocytic lesion, which may be either benign or malignant. CONCLUSION: This case of Meyerson phenomenon revealing melanoma shows that the melanocytic lesions targeted by MP are not necessarily benign.

Kaposi's sarcoma after long-acting steroids: time until remission and drug washout.

Long-acting steroids (LAS) are widely used to treat various inflammatory diseases and allergies. They have many adverse effects including the inhibition of the hypothalamopituitary axis that can last several months. LAS are also strong immunosuppressors and can result in severe opportunistic infections and immunodeficiency-related malignancies. However, the time needed for immune recovery after withdrawal of LAS is unknown. Here we report a case of Kaposi's sarcoma (KS) and severe immunosuppression after a chronic triamcinolone acetonide (TA) treatment. Six months after withdrawal, traces of TA were still detected in the serum by HPLC mass spectrometry. At 8 months, the drug became undetectable, and clinical and biological signs of immune recovery - beginning of KS regression, normalization of IgG levels and CD4 T lymphocyte counts - became noticeable. We then provide a review of the literature on the time until remission of KS after immunosuppression reduction. We also reviewed the cases of KS induced by TA, and the metabolic side effects of TA when compared to standard glucocorticoids.

[The value of radiological follow-up for stage III melanoma]. / Intérêt du suivi radiologique pour les mélanomes au stade III.

INTRODUCTION: The modalities of follow-up (frequency of consultations and interest of repeated radiological examinations) of patients presenting with glandular metastases of melanoma (stage III of the AJCC classification) have not reached a consensus. PATIENTS AND METHODS: Since 1995, we have proposed clinical follow-up every two months and radiological controls with a thoracic-abdominal-pelvic scan every 4 months, to patients at high risk of relapse for the early screening of an infra-clinical relapse. RESULTS: The median follow-up was of 16 months (range: 1 to 82 months). Eight patients out of 24 (33 p. 100) followed-up in this manner, had asymptomatic metastases discovered by the radiological examinations. Among these 8 patients, three presented with a an operable, single, metastatic localization and two patients underwent surgery. One patient relapsed 3 months later, the other was still alive without relapse 24 months later. DISCUSSION: Surgery remains the treatment of choice for all stages of melanoma. In the absence of clearly effective treatment of metastatic melanoma, the early discovery of an infra-clinical metastatic relapse presents two major advantages. The first is the discovery of a single, operable metastasis, as was the case in two of the patients out of 24. The second is to be able to suspend an eventual adjuvant therapy with interferon alpha, as soon as a relapse has been discovered.

Exosomes for immunotherapy of cancer.

Exosomes are 60 to 90 nm membrane vesicles originating from late endosomes and secreted from most hematopoietic and epithelial cells in vitro. B cell derived-exosome antigenicity was first reported in 1996 in MHC class II restricted CD4+ T lymphocytes. In 1998, we reported that dendritic cell derived-exosomes are immunogenic in mice leading to tumor rejection. These findings have renewed the interest in exosomes. The current challenge consists in understanding the mechanisms and the physiological relevance of exosomes that could contribute to the design of the optimal exosome based-vaccination. Here, we will focus on the biological features pertaining to dendritic cell- and tumor cell derived-exosomes and will discuss their potential clinical implementation.

Tumor-derived exosomes: a new source of tumor rejection antigens.

Exosomes are small vesicles released by a broad array of hematopoietic cells. Previous studies showed that exosomes released by antigen loaded dendritic cells induce immune-mediated anti-tumor response in mice. Here, we will describe the biochemical properties of tumor-derived exosomes and, their pre-clinical activity as cancer vaccines.

Successful treatment in two cases of steroid-dependent cutaneous polyarteritis nodosa with low-dose methotrexate.

To the best of our knowledge, only 3 cases of cutaneous polyarteritis nodosa (PAN) treated successfully with methotrexate (MTX) have been reported in the medical literature. We report 2 further cases of steroid-dependent cutaneous PAN treated successfully with low-dose weekly MTX therapy. The clinical and biological tolerance of MTX was excellent. The cutaneous lesions started to regress within 3 weeks. One of the patients reported full recovery which lasted 2 years after stopping the therapy. So, MTX seems to be an interesting therapy in the treatment of PAN because of its relatively low toxicity, its simple use, its quick action and prolonged results after MTX has been stopped.