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We report the case of an 83-year-old French woman with multiple melanomas showing a severe DNA repair deficiency, corrected after transfection by XPC cDNA. Two biallelic mutations in the XPC gene are reported: an inactivating frameshift mutation in exon 15 (c.2544delG, p.W848X) and a missense mutation in exon 11 (c.2108 C>T, P703L). We demonstrate that these new mutations are involved in the DNA repair deficiency and confirm the diagnosis of xeroderma pigmentosum from complementation group C (XP-C). We speculate that the coexistence of a MC1R variant may be involved in the phenotype of multiple melanomas and that the unusual long-term survival may be related to a lower ultraviolet radiation exposure and to a regular clinical follow-up. This patient appears to be the first French Caucasian XP-C case and one of the oldest living patients with XP reported worldwide.

Background: Kaposi sarcoma (KS) occurs mainly in immunocompromised patients and is strongly associated with infection with human herpesvirus 8 (HHV-8; also known as "KS-associated herpesvirus"). We hypothesized that KS is linked to deficiencies in specific anti-HHV-8 T cell immunity., Methods: We studied asymptomatic HHV-8 carriers coinfected with human immunodeficiency virus (HIV; n = 23) and patients with HIV-related or classic KS (n = 29). We used an interferon- gamma enzyme-linked immunospot assay with 56 specific peptides distributed on 6 HHV-8 proteins (glycoprotein [gp] B, gpH, gp35/37, latent nuclear antigen 1 [LANA-1], K12, and K15) to detect HHV-8-specific T cell responses., Results: We found that patients with KS responded to these peptides less often and had much lower HHV-8-specific T cells counts than did asymptomatic HHV-8 carriers (P = .001 and P = .0004, respectively), regardless of CD4 T cell count or HHV-8 load. The frequency of Epstein-Barr virus-specific T cells was similar in both groups., Conclusions: Our results suggest that HIV-related and classic KS are associated with a lack of HHV-8-specific T cells. Also, we have described 8 new HHV-8 T cell epitopes in LANA-1, K12, and K15, including 2 CD4 T cell epitopes. These data provide new insight into HHV-8 cellular immunity.

To assess the clinical and biological benefit of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma (KS), 13 patients with AIDS-associated Kaposi's sarcoma (five pulmonary KS and eight cutaneous KS) were prospectively followed for a mean duration of 12 months. Six patients were treated with specific anti-KS chemotherapy before or simultaneously with the introduction of antiretroviral therapy. Clinical response was assessed according to the AIDS Clinical Trial Group (ACTG) criteria. CD4 cell counts, plasma HIV-1 RNA and human herpesvirus 8 (HHV-8) viraemia were measured at baseline and at different points. Among patients with pulmonary KS, we observed three complete responses (CR), one partial response (PR) and one progression. The median survival time after the diagnosis of pulmonary KS was 15 months with a median duration of the response after the discontinuation of specific chemotherapy for KS of 8 months. Among patients with cutaneous KS, we observed four CR, three PR and one stable response. A complete response was significantly associated with a reversal in HHV-8 viraemia (five of six vs. one of six; P = 0.02, Mann-Whitney test).

Human herpesvirus 8 (HHV-8) is a new virus which has been reported in Kaposi's sarcoma and some lymphoproliferative disorders such as Castleman's disease and body-cavity-based lymphoma. Because HHV-8 shares homology with Epstein-Barr virus (EBV), we searched for the presence of HHV-8 DNA sequences in various cutaneous T- and B-cell lymphoma by the polymerase chain reaction (PCR). Forty-seven HIV-negative patients with cutaneous lymphoma or large plaque parapsoriasis were enrolled in the study. For the detection of HHV-8 DNA sequences we used PCR followed by a hybridization with a digoxigenin-labelled probe and nested-PCR. HHV-8 DNA sequences could only be detected in a patient with large plaque parapsoriasis. Our study does not suggest any direct implication of HHV-8 in the pathogenesis of most cutaneous lymphoma. Serological studies will be helpful to appreciate if there is an epidemiological link between HHV-8 and cutaneous lymphomas.

The epidemiologic link between multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) and the high frequency of KS herpesvirus (KSHV) detection in both diseases raise the question of a role of this new virus in the pathogenesis of MCD. To explore this hypothesis, the KSHV DNA load was investigated in peripheral blood mononuclear cells of 3 human immunodeficiency virus (HIV)-infected patients with MCD at different points during the clinical course. Clinical parameters, such as fever and the presence of lymphadenopathy, were systematically assessed. Hemogram and C-reactive protein level determinations were performed as standard procedures. KSHV DNA load was investigated by means of semiquantitative polymerase chain reaction assay using peripheral blood mononuclear cells of the patients. A correlation between the variation in clinical and biologic parameters related to MCD and KSHV DNA load was found, suggesting a close relationship between KSHV and MCD in HIV-1-infected patients.