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ABSTRACT: Most cases of human immunodeficiency virus (HIV)-associated non-Hodgkin Lymphoma (NHL) are of B-cell origin; T-cell NHLs are rarely reported. Within a single centre prospective cohort of 370 HIV-NHL, 17 (5%) were of T-cell origin (82% male; median age, 39 years). Median CD4+ cell count was 0·194 × 10(9) /l and 41% had undetectable plasma HIV-RNA at lymphoma diagnosis. All patients received combination antiretroviral therapy during chemotherapy. All histological samples were centrally reviewed. The distribution of the histological subtypes differed from the general population with absence of angioimmunoblastic subtype. Lymphoma was disseminated in 14 patients, and seven patients had performance status >2. All patients received full-dose chemotherapy: eight standard and nine intensive regimens. Two patients who received intensive chemotherapy died during therapy. The complete remission rate was 53%; 62·5% with standard therapy and 44% with intensive therapy. After a median follow-up of 7·2 years, the median overall survival was 9·4 months. Most deaths (85%) occurred within the first year following diagnosis, as a consequence of lymphoma progression in 10/13 cases. In this rare but severe complication of HIV infection the use of intensive chemotherapy does not appear to be beneficial for response, with increased toxicity.
British Journal of Haematology 04/2013; · 4.94 Impact Factor
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Jean-Nicolas Boursiquot,
Laurence Gérard,
Marion Malphettes,
Claire Fieschi,
Lionel Galicier,
David Boutboul,
Raphael Borie,
Jean-François Viallard,
Pauline Soulas-Sprauel,
Alice Berezne,
Arnaud Jaccard,
Eric Hachulla,
Julien Haroche,
Nicolas Schleinitz,
Laurent Têtu, Eric Oksenhendler
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ABSTRACT: BACKGROUND: Granulomatous disease (GD) will develop in a subset of patients with common variable immunodeficiency (CVID). Little is known about the efficacy of therapeutic agents used for treating this disorder. OBJECTIVE: To evaluate the efficacy of immunosuppressive drugs with the help of a set of clinical, biological and radiological criteria. METHOD: Clinical and laboratory features of CVID patients were collected from the French DEFI cohort, a prospective study on adults with hypogammaglobulinemia. The medical charts of 55 patients (93 %) of the GD cohort were reviewed. RESULTS: Among 436 subjects with CVID, 59 patients (13.5 %) were diagnosed with GD. Of the 55 patients in whom medical charts were available, 32 patients received treatment for the granulomatous disease. Corticosteroids were the most frequently used drug. Complete response to treatment was infrequent. It was achieved with corticosteroids, cyclophosphamide, hydroxychloroquine, rituximab and methotrexate. Azathioprine, cyclosporine, mycophenolate mofetil, sirolimus, infliximab and thalidomide led to partial or absence of response. Complete and partial responses were observed in lymph nodes, lungs, liver, skin, bone marrow and central nervous system. Absent of response for gastrointestinal tract granulomas was noted in all cases of treatment attempt. CONCLUSION: CVID patients with GD exhibit a particular biological phenotype. Treatment should be considered in any symptomatic patient or if there is evidence of organ dysfunction. Corticosteroids are the drug of choice in most instances but response to treatment is often unsatisfactory.
Journal of Clinical Immunology 09/2012; · 3.08 Impact Factor
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JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2012; 60(5):e121-2. · 4.43 Impact Factor
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Marie-Olivia Chandesris,
Isabelle Melki,
Angels Natividad,
Anne Puel,
Claire Fieschi,
Ling Yun,
Caroline Thumerelle, Eric Oksenhendler,
David Boutboul,
Caroline Thomas, [......],
Monique Forveille,
Marie-Alexandra Alyanakian,
Anne Durandy,
Christine Bodemer,
Felipe Suarez,
Olivier Hermine,
Olivier Lortholary,
Jean-Laurent Casanova,
Alain Fischer,
Capucine Picard
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ABSTRACT: Autosomal dominant deficiency of signal transducer and activator of transcription 3 (STAT3) is the main genetic etiology of hyper-immunoglobulin (Ig) E syndrome. We documented the molecular, cellular, and clinical features of 60 patients with heterozygous STAT3 mutations from 47 kindreds followed in France. We identified 11 known and 13 new mutations of STAT3. Low levels of interleukin (IL)-6-dependent phosphorylation and nuclear translocation (or accumulation) of STAT3 were observed in Epstein-Barr virus-transformed B lymphocytes (EBV-B cells) from all STAT3-deficient patients tested. The immunologic phenotype was characterized by high serum IgE levels (96% of the patients), memory B-cell lymphopenia (94.5%), and hypereosinophilia (80%). A low proportion of IL-17A-producing circulating T cells was found in 14 of the 15 patients tested. Mucocutaneous infections were the most frequent, typically caused by Staphylococcus aureus (all patients) and Candida albicans (85%). Up to 90% of the patients had pneumonia, mostly caused by Staph. aureus (31%) or Streptococcus pneumoniae (30%). Recurrent pneumonia was associated with secondary bronchiectasis and pneumatocele (67%), as well as secondary aspergillosis (22%). Up to 92% of the patients had dermatitis and connective tissue abnormalities, with facial dysmorphism (95%), retention of decidual teeth (65%), osteopenia (50%), and hyperextensibility (50%). Four patients developed non-Hodgkin lymphoma. The clinical outcome was favorable, with 56 patients, including 43 adults, still alive at the end of study (mean age, 21 yr; range, 1 mo to 46 yr). Only 4 patients died, 3 from severe bacterial infection (aged 1, 15, and 29 yr, respectively). Antibiotic prophylaxis (90% of patients), antifungal prophylaxis (50%), and IgG infusions (53%) improved patient health, as demonstrated by the large decrease in pneumonia recurrence. Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic measures, including IgG infusions, are implemented.
Medicine 06/2012; 91(4):e1-19. · 4.35 Impact Factor
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Laurence Gérard,
Jean-Marie Michot,
Sara Burcheri,
Claire Fieschi,
Pacale Longuet,
Véronique Delcey,
Véronique Meignin,
Felix Agbalika,
Sylvie Chevret, Eric Oksenhendler,
Lionel Galicier
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ABSTRACT: HIV-associated multicentric Castleman disease (MCD) is associated with a high risk of developing non-Hodgkin lymphoma (NHL). Rituximab is effective in HIV-MCD, but its impact on NHL incidence remains unknown. From a single-center prospective cohort, 113 patients were identified with a diagnosis of HIV-MCD for the present study. To compare the incidence of NHL between patients who had received a rituximab-based treatment (R+ group) and those who had not (R- group), data were analyzed before and after matching on propensity scores and after multiple imputation. The mean follow-up was 4.2 years. In the R- group (n = 65), 17 patients developed NHL (incidence, 69.6 of 1000 person years). In the R+ group (n = 48), only 1 patient developed NHL (incidence, 4.2 of 1000 person years). Based on the propensity score-matching method, a significant decrease in the incidence of NHL was observed in patients who had been treated with rituximab (hazard ratio, 0.09; 95% confidence interval, 0.01-0.70). Ten Kaposi sarcoma (KS) exacerbations and 1 newly diagnosed KS were observed in 9 patients after rituximab therapy. Rituximab was associated with an 11-fold lower risk of developing lymphoma. KS exacerbation was the most challenging adverse event after rituximab therapy.
Blood 03/2012; 119(10):2228-33. · 9.90 Impact Factor
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Claire Rivoisy,
Laurence Gérard,
David Boutboul,
Marion Malphettes,
Claire Fieschi,
Isabelle Durieu,
François Tron,
Agathe Masseau,
Pierre Bordigoni,
Laurent Alric,
Julien Haroche,
Cyrille Hoarau,
Alice Bérézné,
Maryvonnick Carmagnat,
Gael Mouillot, Eric Oksenhendler
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ABSTRACT: The DEFI study has collected clinical data and biological specimens from kindreds with CVID. Patients with demonstrated parental consanguinity (cCVID group) were compared to patients without parental consanguinity (ncCVID). A total of 24 of the 436 patients with CVID had consanguineous parents. Age at first symptoms and age at diagnosis were comparable in the two groups. Some complications were more frequent in cCVID patients: splenomegaly (62.5% vs. 29%; p = 0.001), granulomatous disease (29% vs. 12%; p = 0.02), and bronchiectasis (58% vs. 29%; p = 0.003). A high incidence of opportunistic infections was also observed in this population (29% vs. 5%; p < 0.001). Distribution of B-cell subsets were similar in the two groups. Naïve CD4+ T cells were decreased in cCVID patients (15% vs. 28%; p < 0.001), while activated CD4 + CD95+ (88% vs. 74%; p = 0.002) and CD8 + HLA-DR + T cells (47% vs. 31%; p < 0.001) were increased in these patients when compared to ncCVID patients. Parental consanguinity is associated with an increased risk of developing severe clinical complications in patients with CVID. Most of these patients presented with severe T-cell abnormalities and should be considered with a diagnosis of late-onset combined immune deficiency (LOCID). Systematic investigation for parental consanguinity in patients with CVID provides useful information for specific clinical care and genetic screening.
Journal of Clinical Immunology 02/2012; 32(1):98-105. · 3.08 Impact Factor
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Sandrine Leroy,
Despina Moshous,
Olivier Cassar,
Yves Reguerre,
Minji Byun,
Vincent Pedergnana,
Danielle Canioni,
Antoine Gessain, Eric Oksenhendler,
Claire Fieschi,
Nizar Mahlaoui,
Jean-Pierre Rivière,
Rose-Marie Herbigneaux,
Matthias Muszlak,
Jean-Pierre Arnaud,
Alain Fischer,
Capucine Picard,
Stéphane Blanche,
Sabine Plancoulaine,
Jean-Laurent Casanova
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ABSTRACT: Childhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection.
PEDIATRICS 12/2011; 129(1):e199-203. · 4.47 Impact Factor
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Romain Micol,
Samer Kayal,
Nizar Mahlaoui,
Julien Beauté,
Pauline Brosselin,
Yasmine Dudoit,
Gaëlle Obenga,
Vincent Barlogis,
Nathalie Aladjidi,
Kamila Kebaili, [......],
Marie-Alexandra Alyanakian,
Capucine Picard,
Stéphane Blanche,
Olivier Hermine,
Felipe Suarez,
Marianne Debré,
Marc Lecuit,
Olivier Lortholary,
Anne Durandy,
Alain Fischer
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ABSTRACT: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]).
This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome.
A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured.
When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections.
IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.
The Journal of allergy and clinical immunology 12/2011; 129(3):770-7. · 9.17 Impact Factor
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ABSTRACT: Enteropathy-associated T-cell lymphoma is a rare form of T-cell lymphoma associated with a poor prognosis and the relative ineffectiveness of standard chemotherapy. The occurrence of haemophagocytic lymphohistiocytosis has been reported only once with this entity.
A retrospective study of 15 patients with enteropathy-associated T-cell lymphoma (type 1 in 12), followed-up in our units, since 1985. Two patients died before starting chemotherapy. The remaining 13 patients were treated with standard chemotherapy (n=7) and purine nucleotide analogues (n=6).
Median follow-up was 8.7 (1-97) months. Surgery was required in 10 patients (66%) for intestinal complications (n=7) or elective small bowel resection (n=3). Survival probability was 40% and 20% at 1 and 5 years, respectively (Kaplan-Meier method). Survival was not significantly different between the two chemotherapy regimens. However, a slight decrease of febrile neutropenia was observed in the purine nucleotide analogues group (p=0.06). Haemophagocytic lymphohistiocytosis occurred in 6/15 (40%) cases. In these six patients, haemophagocytic lymphohistiocytosis was always fatal within 3 months.
Enteropathy-associated T-cell lymphoma is associated with a poor outcome, independently of the chemotherapy regimens administered and frequent occurrence of haemophagocytic lymphohistiocytosis. The latter complication should be considered for urgent rescue therapy.
Digestive and Liver Disease 11/2011; 44(4):343-9. · 3.05 Impact Factor
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Bénédicte Neven,
Aude Magerus-Chatinet,
Benoit Florkin,
Delphine Gobert,
Olivier Lambotte,
Lien De Somer,
Nina Lanzarotti,
Marie-Claude Stolzenberg,
Brigitte Bader-Meunier,
Nathalie Aladjidi, [......],
Eric Jeziorski,
Guy Leverger,
Gérard Michel,
Felipe Suarez, Eric Oksenhendler,
Olivier Hermine,
Stéphane Blanche,
Capucine Picard,
Alain Fischer,
Frédéric Rieux-Laucat
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ABSTRACT: Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder characterized by early-onset, chronic, nonmalignant lymphoproliferation, autoimmune manifestations, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline (ALPS-FAS) or somatic mutations (ALPS-sFAS) of the TNFRSF6 gene coding for FAS. Although the clinical features of ALPS have been described previously, long-term follow-up data on morbidity and mortality are scarce. We performed a retrospective analysis of clinical and genetic features of 90 ALPS-FAS and ALPS-sFAS patients monitored over a median period of 20.5 years. Heterozygous germline mutations of TNFRSF6 were identified in 83% of probands. Somatic TNFRSF6 mutations were found in 17% of index cases (all located within the intracellular domain of FAS). Sixty percent of the ALPS-FAS patients with mutations in the extracellular domain had a somatic mutation affecting the second allele of TNFRSF6; age at onset was later in these patients. No other genotype-phenotype correlations could be found. Long-term analysis confirmed a trend toward spontaneous remission of lymphoproliferation in adulthood but mixed outcomes for autoimmune manifestations. We observed significant and potentially life-threatening disease and treatment-related morbidity, including a high risk of sepsis after splenectomy that calls for careful long-term monitoring of ALPS patients. We also noted a significantly greater occurrence of disease-related symptoms in male than in female patients.
Blood 09/2011; 118(18):4798-807. · 9.90 Impact Factor
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Raphael Szalat,
Bertrand Arnulf,
Lionel Karlin,
Michel Rybojad,
Bouchra Asli,
Marion Malphettes,
Lionel Galicier,
Marie-Dominique Vignon-Pennamen,
Stéphanie Harel,
Florence Cordoliani,
Jean Gabriel Fuzibet, Eric Oksenhendler,
Jean-Pierre Clauvel,
Jean-Claude Brouet,
Jean-Paul Fermand
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ABSTRACT: Xanthomas are a common manifestation of lipid metabolism disorders. They include hyperlipemic xanthoma, normolipemic xanthoma, and a related condition, necrobiotic xanthogranuloma (NXG). All 3 forms can be associated with monoclonal immunoglobulin (MIg). In an attempt to improve diagnosis, understanding, and treatment of this association, we retrospectively analyzed a personal series of 24 patients (2 hyperlipemic xanthoma, 11 normolipemic xanthoma, and 11 NXG) and 230 well-documented reports from the literature. With the exception of the nodules and plaques featured in NXG, the clinical presentation of xanthomatous lesions usually resembled that seen in common hyperlipidemic forms and could not be used to suspect MIg-associated xanthomas. Extracutaneous sites were not rare. The MIg was an IgG in 80% of cases. Myeloma was diagnosed in 35%. Hypocomplementemia with low C4 fraction was present in 80% of studied patients. Low C1 inhibitor serum levels were found in 53%. Cryoglobulinemia was detected in 27%. These abnormalities suggest immune complex formation because of interactions between the MIg and lipoproteins and argue in favor of a causal link between MIg and xanthomas. Monoclonal gammopathy therapy could thus be an option. Indeed, among the patients who received chemotherapy, hematologic remission was accompanied by improvement in xanthoma lesions in several cases.
Blood 07/2011; 118(14):3777-84. · 9.90 Impact Factor
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Nicolas Vince,
David Boutboul,
Gael Mouillot,
Nicolas Just,
Maria Peralta,
Jean-Laurent Casanova,
Mary Ellen Conley,
Jean-Christophe Bories, Eric Oksenhendler,
Marion Malphettes,
Claire Fieschi
The Journal of allergy and clinical immunology 02/2011; 127(2):538-541.e1-5. · 9.17 Impact Factor
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Emilie Lanoy,
Jean-Philippe Spano,
Fabrice Bonnet,
Marguerite Guiguet,
François Boué,
Jacques Cadranel,
Guislaine Carcelain,
Louis-Jean Couderc,
Pierre Frange,
Pierre-Marie Girard, Eric Oksenhendler,
Isabelle Poizot-Martin,
Caroline Semaille,
Henri Agut,
Christine Katlama,
Dominique Costagliola
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ABSTRACT: Since no large descriptive studies of incident cancers in HIV-infected patients are available in France, the nationwide cross-sectional ONCOVIH study aimed to prospectively report new malignancies diagnosed in HIV-infected patients in cancer centers and HIV/AIDS centers. We estimated the number of cancers in France for the year 2006 using the capture-recapture methods with two sources: ONCOVIH and the FHDH ANRS-CO4 cohort, as well as the completeness of the sources. Incidence and relative risks (RR) to the general population were estimated. In 2006, 672 new malignancies in 668 patients were reported in ONCOVIH; the most common were non Hodgkin's lymphoma (NHL, 21.5%), Kaposi's sarcoma (KS, 16.0%), lung cancer (9.4%), anal cancer (8.2%), Hodgkin's lymphoma (7.6%), skin cancers excluding melanoma (6.8%), and liver cancer (5.6%). Based on the capture-recapture approach, the estimated number of malignancies was 1320 and non-AIDS-defining malignancies (NADM) represented 68% of cases. The overall ascertainment of malignancies were 53%, and 59%, in the ONCOVIH study, and the FHDH ANRS-CO4 cohort, respectively. The estimated incidence of cancer among HIV-infected patients was 14 per 1000 person-years. Compared with the general population, the estimated RR in HIV-infected patients was 3.5 (95%CI 3.3-3.8) in men and 3.6 (95%CI 3.2-4.0) in women, and was particularly elevated in younger patients. Even in the era of combined antiretroviral therapy, the incidence of cancer is higher in HIV-infected persons than in the general population. A large variety of malignancies were diagnosed, and the majority were NADM.
International Journal of Cancer 01/2011; 129(2):467-75. · 5.44 Impact Factor
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ABSTRACT: Common variable immunodeficiency (CVID) is the most frequent clinically expressed primary immunodeficiency in adults and is characterized by primary defective immunoglobulin production. Besides recurrent infectious manifestations, up to 20% of CVID patients develop autoimmune complications. In this study, we took advantages of the French DEFI database to investigate possible correlations between peripheral lymphocyte subpopulations and autoimmune clinical expression in CVID adult patients. In order to analyse homogeneous populations of patients with precise clinical phenotypes, we first focused on patients with autoimmune cytopenia because they represent prototypic autoantibody mediated diseases. In a secondary analysis, we have tested our conclusions including all "autoimmune" CVID patients. We describe one of the largest European studies with 311 CVID patients, including 55 patients with autoimmune cytopenia and 61 patients with clinical or serologic autoimmune expression, excluding autoimmune cytopenia. We clarify previous reports and we confirm a very significant correlation between an increased proportion of CD21(low) B cells and CVID associated autoimmune cytopenia, but independently of the presence of other autoimmune disorders or of splenomegaly. Moreover, in CVID associated autoimmune cytopenia, T cells display an activated phenotype with an increase of HLA-DR and CD95 expression and a decrease in the naïve T cell numbers. Patients with other autoimmune manifestations do not harbour this "T and B cells phenotypic picture". In view of recent findings on CD21(low) B cells in CVID and RA, we suggest that both a restricted subset of B cells and a T cell help are required for a breakdown of B cell tolerance against membrane auto antigens in CVID.
Journal of Autoimmunity 11/2010; 36(1):25-32. · 7.37 Impact Factor
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Jagadeesh Bayry,
Emilie M Fournier,
Mohan S Maddur,
Janakiraman Vani,
Bharath Wootla,
Sophie Sibéril,
Jordan D Dimitrov,
Sébastien Lacroix-Desmazes,
Mikael Berdah,
Yoann Crabol, Eric Oksenhendler,
Yves Lévy,
Luc Mouthon,
Catherine Sautès-Fridman,
Olivier Hermine,
Srini V Kaveri
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ABSTRACT: Common variable immunodeficiency (CVID) is associated with low serum immunoglobulin concentrations and an increased susceptibility to infections and autoimmune diseases. The treatment of choice for CVID patients is replacement intravenous immunoglobulin (IVIg) therapy. IVIg has been beneficial in preventing or alleviating the severity of infections and autoimmune and inflammatory process in majority of CVID patients. Although the mechanisms of action of IVIg given as 'therapeutic high dose' in patients with autoimmune diseases are well studied, the underlying mechanisms of beneficial effects of IVIg in primary immunodeficiencies are not completely understood. Therefore we investigated the effect of 'replacement dose' of IVIg by probing its action on B cells from CVID patients. We demonstrate that IVIg at low doses induces proliferation and immunoglobulin synthesis from B cells of CVID patients. Interestingly, B cell stimulation by IVIg is not associated with induction of B cell effector cytokine IFN-γ and of transcription factor T-bet. Together, our results indicate that in some CVID patients, IVIg rectifies the defective signaling of B cells normally provided by T cells and delivers T-independent signaling for B cells to proliferate. IVIg 'replacement therapy' in primary immunodeficiencies is therefore not a merepassive transfer of antibodies to prevent exclusively the recurrent infections; rather it has an active role in regulating autoimmune and inflammatory responses through modulating B cell functions and thus imposing dynamic equilibrium of the immune system.
Journal of Autoimmunity 10/2010; 36(1):9-15. · 7.37 Impact Factor
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Emilie Sbidian,
Maxime Battistella,
Jacqueline Rivet,
Béatrice Flageul,
Jean-Michel Molina,
Pascal Joly,
Eric Caumes,
Guy Gorochov,
Jean-Michel Cayuela,
Claire Rabian,
Nicolas Dupin,
Céleste Lebbé,
Anne Janin,
Michel Janier, Eric Oksenhendler,
Hervé Bachelez
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ABSTRACT: A CD8 cutaneous lymphoinfiltrative disease has been described in human immunodeficiency virus (HIV)-infected patients presenting with a severe erythroderma. The true nature of this severe skin infiltrative disorder is still elusive. Although some clinical features of this syndrome have raised the hypothesis of its malignant nature in initial observations, several studies have provided stronger support to the hypothesis that it is a reactive pseudotumoral process.
From 1995 through 2008, 8 HIV type 1 (HIV-1)-infected patients presenting with a chronic skin eruption, diagnosed as CD8 T cell infiltration of the skin, were studied.
All patients showed diffuse infiltrated skin with superficial lymphadenopathy. A profound CD4(+) lymphocytopenia and eosinophilia were other major features. Histological and immunostaining analysis revealed a predominant dermal and epidermal infiltration by CD8(+) T cells belonging to the cytotoxic lineage, without evidence for a monoclonal status by polymerase chain reaction-based molecular analysis of lesional skin. A remission of skin symptoms occurred in all cases following highly active antiretroviral therapy, which paralleled the decrease of HIV-1 RNA load and the increase of CD4(+) peripheral blood absolute count.
Altogether, these results emphasize the reactive, nonmalignant nature of this syndrome and strongly support the coupling between HIV-induced immune deficiency and uncontrolled CD8 activation.
Clinical Infectious Diseases 09/2010; 51(6):741-8. · 9.15 Impact Factor
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Sylvain Thépot,
Marion Malphettes,
Anaëlle Gardeur,
Lionel Galicier,
Bouchra Asli,
Lionel Karlin,
Laurence Gérard,
Richard Laumont,
Marie-Laure Doize,
Bertrand Arnulf,
Claire Fieschi,
Djaouïda Bengoufa, Eric Oksenhendler
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ABSTRACT: The impact of reducing immunoglobulin dosage while switching from intravenous to subcutaneous replacement therapy was evaluated.
Sixty-five patients with primary hypogammaglobulinemia on stable intravenous replacement therapy were included in a monocentric longitudinal trial. IgG trough levels were measured at baseline and during 1 year following the switch to the subcutaneous route.
Mean IgG trough level after 12 months of subcutaneous therapy was increased by 5.4 percent (8.37-8.82 g/l, p=0.3), while immunoglobulin dosage had been reduced by 28.3% (151-108 mg/kg/week, p<0.0001). For the patients with the lowest serum IgG level upon intravenous infusions, serum IgG level rose by 37 percent (5.33-7.33 g/l, p=0.003), while mean immunoglobulin dosage was reduced by 36 percent (170-109 mg/kg/week, p=0.04).
The present study shows that sustained serum IgG levels can be achieved after switching towards subcutaneous replacement despite using reduced immunoglobulin doses.
Journal of Clinical Immunology 07/2010; 30(4):602-6. · 3.08 Impact Factor
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Gaël Mouillot,
Maryvonnick Carmagnat,
Laurence Gérard,
Jean-Luc Garnier,
Claire Fieschi,
Nicolas Vince,
Lionel Karlin,
Jean-François Viallard,
Roland Jaussaud,
Julien Boileau, [......],
Eric Hachulla,
Karen Delavigne,
Martine Morisset,
Serge Jacquot,
Nicolas Just,
Lionel Galicier,
Dominique Charron,
Patrice Debré, Eric Oksenhendler,
Claire Rabian
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ABSTRACT: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent infections and defective immunoglobulin production.
The DEFI French national prospective study investigated peripheral T-cell and B-cell compartments in 313 CVID patients grouped according to their clinical phenotype, using flow cytometry.
In patients developing infection only (IO), the main B-cell or T-cell abnormalities were a defect in switched memory B cells and a decrease in naive CD4(+) T cells associated with an increase in CD4(+)CD95(+) cells. These abnormalities were more pronounced in patients developing lymphoproliferation (LP), autoimmune cytopenia (AC), or chronic enteropathy (CE). Moreover, LP and AC patients presented an increase in CD21(low) B cells and CD4(+)HLA-DR(+) T cells and a decrease in regulatory T cells.
In these large series of CVID patients, the major abnormalities of the B-cell and T-cell compartments, although a hallmark of CVID, were only observed in half of the IO patients and were more frequent and severe in patients with additional lymphoproliferative, autoimmune, and digestive complications.
Journal of Clinical Immunology 05/2010; 30(5):746-55. · 3.08 Impact Factor
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Marion Malphettes,
Laurence Gérard,
Maryvonnick Carmagnat,
Gaël Mouillot,
Nicolas Vince,
David Boutboul,
Alice Bérezné,
Raphaële Nove-Josserand,
Vincent Lemoing,
Laurent Tetu,
Jean-François Viallard,
Bernard Bonnotte,
Michel Pavic,
Julien Haroche,
Claire Larroche,
Jean-Claude Brouet,
Jean-Paul Fermand,
Claire Rabian,
Claire Fieschi, Eric Oksenhendler
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ABSTRACT: Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs).
The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs.
Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count <200 x 10(6) cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P = .004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4(+) T cell counts (158 x 10(6) vs 604 x 10(6) cells/L; P < .001) and a severe defect in naive CD45RA(+)CCR7(+)CD4(+) T cell counts (<20% of total CD4(+) T cells in 71% of patients with LOCID vs 37% of patients with CVID; P = .001). The CD19(+) B cell compartment was also significantly decreased (20 x 10(6) vs 102 x 10(6) cells/L; P < .001).
LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis.
Clinical Infectious Diseases 11/2009; 49(9):1329-38. · 9.15 Impact Factor
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ABSTRACT: Despite effective treatment of HIV infection, some patients still develop non-Hodgkin lymphoma (NHL). We analysed patients with HIV-associated NHL and undetectable plasma HIV-RNA, according to the duration of HIV suppression.
Out of 388 patients included in a prospective cohort of HIV-associated NHL from 1996 to 2008, 128 (33%) had a plasma HIV-RNA below 500 copies/ml and were included in the study. Patients with long-term HIV suppression (>18 months) were compared with patients with recent HIV suppression (< or = 18 months).
All patients but three were treated with combination antiretroviral therapy, with a median duration of 2.2 years. The median duration of HIV suppression was 10.1 months. Most cases (65%) occurred within 18 months following HIV suppression. In the more than 18 months group, patients developed NHL at a higher CD4 cell count than patients with 18 months or less of HIV suppression (359 versus 270 cells/microl, P = 0.02). None of the NHL characteristics were different between the two groups. Outcome was similar in the two groups (complete remission, 64 versus 72.5%; P = 0.35 and 3-year survival, 46 versus 56%; P = 0.08). In addition, 52% of the tumours were Epstein-Barr virus or human herpesvirus 8 associated, without any difference in the proportion of virus-associated tumours according to the duration of HIV suppression.
In patients with undetectable HIV-RNA, NHL occurred mainly within the first 18 months following HIV suppression. In patients developing NHL after long-term HIV suppression, the level of CD4 cell count was higher, but the association with Epstein-Barr virus or human herpesvirus 8 and the prognosis were similar to that observed in patients with recent HIV suppression.
AIDS (London, England) 09/2009; 23(17):2301-8. · 4.91 Impact Factor
