Summary Background & aims Healthcare-associated infections HAI are common in elderly individuals and may be related to both nutritional deficiencies and immunosenescence. Here, we assessed whether ...overall malnutrition and/or specific nutrient deficiencies were associated with HAI via alterations in immune parameters. Methods Prospective observational cohort study in patients aged ≥70 years admitted to the geriatric rehabilitation unit of a teaching hospital in France between July 2006 and November 2008. Clinical and laboratory parameters reflecting nutritional status and immune function were collected at baseline. Flow cytometry was used to assess blood lymphocyte subsets including the naive CD4 T-cell count, naive and memory CD8 T-cell counts, effector CD8 T-cell count, and CD4/CD8 ratio. Patients were monitored for HAI for 3 months or until discharge from the geriatric unit or death. Results Of 252 consecutive in-patients aged ≥70 years mean age, 85 ± 6.2 years, 181 72% met French National Authority for Health criteria for malnutrition and 97 38% experienced one or more HAI. Patients who subsequently experienced HAI had significantly lower baseline values for energy intake odds ratio (OR), 0.76; 95% confidence interval (95%CI), 0.59–0.99, serum albumin OR, 0.43; 95%CI, 0.32–0.58, serum zinc OR, 0.77; 95%CI, 0.62–0.97, selenium OR, 0.76; 95%CI, 0.61–0.95, and vitamin C OR, 0.71; 95%CI, 0.54–0.93. Associations linking these five variables to HAI were not significantly changed by adjusting for flow cytometry T-cell subset values. Conclusion Our results suggest a direct effect of nutritional parameters on HAI rather than an indirect effect mediated by immune parameters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
1 Etablissement Français du Sang, Ile de France, Hôpital Henri Mondor, Créteil;
2 Centre de Référence des Cytopénies Auto-Immunes, Hôpital Henri Mondor, Créteil;
3 Service des Maladies Génétiques du ...Globule Rouge, Hôpital Henri Mondor Créteil;
4 Service de Médecine Interne, Hôpital Henri Mondor, Créteil;
5 Laboratoire dImmunologie, Hôpital Henri Mondor, Créteil;
6 Université de Poitiers, EA 3806, CHU de Poitiers
Correspondence: France Noizat-Pirenne, MD, PhD, Etablissement Français du Sang dIle de France, 51 Avenue du Maréchal de Lattre de Tassigny, 94000, Créteil, France. Tel: 331 56 72 76 37; Fax: 331 56 72 76 01, E-mail: france.noizat-pirenne{at}efs.sante.fr
Delayed hemolytic transfusion reaction (DHTR), a life-threatening transfusion complication in sickle cell disease (SCD), is characterized by a marked hemoglobin drop with destruction of both transfused and autologous red blood cells (RBCs) and exacerbation of SCD symptoms. One mechanism of RBCs destruction is auto-antibody production secondary to transfusion. As rituximab specifically targets circulating B cells, we thought that it could be beneficial in preventing this immune-mediated transfusion complication. We report the case of a SCD patient who previously experienced DHTR with auto-antibodies and who needed a new transfusion. DHTR recurrence was successfully prevented by rituximab administration prior transfusion, supporting the safe use of rituximab to prevent DHTR in SCD patients as a second line approach when other measures failed.
Key words: Sickle cell disease, rituximab, transfusion, auto-antibodies.
Central nervous system (CNS) relapse is an uncommon but dramatic complication of diffuse large B-cell lymphoma (DLBCL). Several studies have demonstrated the superiority of cerebrospinal fluid (CSF) ...flow cytometry (FCM), as compared with conventional cytology (CC), in detecting occult leptomeningeal disease. The clinical relevance of a positive FCM still has to be clarified.
We analyzed CSF from 114 DLBCL patients at diagnosis (n = 95) or at relapse (n = 19) by FCM and CC. Most patients received meningeal prophylaxis. FCM results did not influence treatment strategies.
Fourteen samples were FCM+, versus one CC+ (also FCM+). Within all patients without neurological symptoms (n = 101), four (4%) relapsed in the CNS, with a median time to relapse of 5.2 months. Only one-fourth (25%) was FCM+ before relapse. More than one extranodal disease site and elevated lactate dehydrogenase levels were associated with an increased risk of CNS relapse.
FCM gives far more positive results than CC. However, a positive FCM result did not translate into a significant increase in CNS relapse rate in this histologically uniform population receiving CNS prophylaxis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Lymphocytopenia is a prognostic factor in Hodgkin's disease. In diffuse large B-cell lymphoma (DLBCL), data are much less established, in spite of numerous reports on immune ...system–lymphoma interactions. This study addresses the prognostic value of blood lymphocyte subsets at diagnosis in DLBCL. Patients and methods: Absolute values of blood lymphocyte subsets and monocytes were prospectively determined by flow cytometry in 140 patients with 2 or 3 adverse age-adjusted International Prognostic Index (aaIPI) factors included in a Groupe d'Etude des Lymphomes de l'Adulte protocol (LNH98B3). Absolute cell counts at diagnosis and aaIPI were evaluated with regard to clinical outcome. Results: Low median cell counts of 337, 211, and 104/μl were evidenced for the CD4+, CD8+ T, and natural killer (NK) cells, respectively. In univariate analysis, only NK cell count odds ratio (OR) = 1.81 (1.27, 2.57), P = 0.001 and aaIPI OR = 2.29 (0.95, 5.45), P = 0.06 were associated with induction treatment response. Low NK cell count Hazard ratio (HR) = 1.27 (1.06, 1.52), P = 0.01 and aaIPI 3 HR = 1.95 (1.20, 3.16), P = 0.01 were also associated with a shorter event free survival (EFS). In multivariate analysis, NK cell count was associated with response OR = 1.77 (1.24, 2.54), P = 0.002 and EFS HR = 1.25 (1.04, 1.50) P = 0.02 independently of aaIPI. Conclusions: This study shows an association between circulating NK cell number and clinical outcome in DLBCL, possibly important in the context of the broadening use of rituximab, a likely NK-dependant therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nosocomial infections are extremely common in the elderly and may be related to ageing of the immune system. The Immune Risk Phenotype (IRP), which predicts shorter survival in elderly patients, has ...not been evaluated as a possible risk factor for nosocomial infection. Our aim was to assess the prevalence of nosocomial infections in elderly in-patients and to investigate potential relationships between nosocomial infections and the immunophenotype, including IRP parameters.
We included 252 consecutive in-patients aged 70 years or over (mean age, 85 ± 6.2 years), between 2006 and 2008. Among them, 97 experienced nosocomial infections, yielding a prevalence rate of 38.5% (95% confidence interval, 32.5-44.5). The main infection sites were the respiratory tract (21%) and urinary tract (17.1%) When we compared immunological parameters including cell counts determined by flow cytometry in the groups with and without nosocomial infections, we found that the group with nosocomial infections had significantly lower values for the CD4/CD8 ratio and naive CD8 and CD4 T-cell counts and higher counts of memory CD8 T-cells with a significant increase in CD28-negative CD8-T cells. Neither cytomegalovirus status (positive in 193/246 patients) nor presence of the IRP was associated with nosocomial infections. However, nosocomial pneumonia was significantly more common among IRP-positive patients than IRP-negative patients (17/60 versus 28/180; p = 0.036).
Immunological parameters that are easy to determine in everyday practice and known to be associated with immune system ageing and shorter survival in the elderly are also associated with an elevated risk of nosocomial pneumonia in the relatively short term.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Infiltration of activated lymphocytes and monocytes is a key phenomenon in the pathogenesis of Guillain–Barré syndrome (GBS) and experimental autoimmune neuritis (EAN). To investigate the role of ...chemokines, we determined the blood and nerve tissue expression of monocyte chemoattractant protein 1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, and its receptor CCR2 in GBS and EAN. MCP-1 circulating levels (ng/ml) in GBS were increased at the time of progression, peaked at the time of plateau and normalized with recovery. MCP-1 circulating levels were the highest in the most disabled patients. The number of circulating CCR2 positive cells was lower in patients with GBS than in healthy subjects (
p<0.004). In GBS, MCP-1 expression was observed in epineurial and endoneurial vessels, on infiltrating cells, Schwann cells and in the endoneurial extracellular matrix. Some CCR2 positive cells were observed in nerve biopsies of GBS patients. In EAN, a slight positivity for MCP-1 was observed in the sciatic nerve. There was no circulating CCR2 positive cells. However, at the time of plateau, a conspicuous infiltration of CCR2 positive cells was observed in the sciatic nerve that was no longer observed at the time of recovery. These results suggest that MCP-1 and CCR2 may participate to the recruitment of circulating mononuclear cells in nerve tissue in EAN and GBS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Skin lesions are frequent in monoclonal cryoglobulinaemia and may be the first sign of B-cell lymphoma, especially multiple myeloma, Waldenström's macroglobulinaemia and B-cell chronic lymphocytic ...leukaemia.
A 74-year-old woman with no prior medical history presented with necrotic leg ulcer. Skin biopsy showed dermal angiomatosis with numerous PAS+ thromboses, associated with monoclonal intravascular deposits of IgM kappa, indicating monoclonal cryoglobulin, which was confirmed by laboratory tests. Subsequent blood immunophenotyping revealed an inconspicuous circulating monoclonal CD5(+) B-cell population and small B-cell clusters in the bone marrow, while the B-cell count was normal and no lymphadenopathy or splenomegaly were present. Overall, these findings indicated a small B-cell lymphoma, classed as non-MALT marginal zone lymphoma on the WHO classification, at a very early stage of development. The patient was first treated by cyclophosphamide and oral steroids without success. Subsequent administration of six cycles of rituximab, cyclophosphamide, vincristine and prednisone (RCVP) led to remission of her leg ulcer, cryoglobulinaemia and lymphoma.
Skin biopsies of necrotic ulcers should undergo routine screening for intravascular deposits of type 1 cryoglobulin. Leg ulcers due to monoclonal cryoglobulinaemia may reveal incipient marginal zone B-cell lymphoma at the stage of circulating monoclonal lymphocytosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor ...tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy.
Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome.
A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06).
We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted.
BACKGROUND: CD36 is expressed on several cell lineages. About 5 to 10 percent of Asians lack platelet membrane CD36 (pCD36), but the frequency of pCD36 deficiency in other ethnic groups is not known. ...Persons who are pCD36‐negative are apparently healthy but can develop CD36 isoimmunization.
STUDY DESIGN AND METHODS: The pCD36 phenotype was studied in 1885 subjects belonging either to a group of 1127 healthy French blood donors (almost all of whom were white Europeans) or to a group of 758 patients of known ethnic origin.
RESULTS: No pCD36‐negative persons were found among the blood donors. Only 1 of the 301 white European patients was pCD36‐negative. In contrast, 16 of the 206 sub‐Saharan Africans was pCD36‐negative, a proportion higher than that among that black Caribbeans (1/148, p<0.01). The frequency of pCD36‐negative patients was similar in blacks with and without sickle cell disease. Monocyte CD36 (mCD36) expression was studied in 15 of 22 pCD36‐negative individuals: it was <10 percent in 7 subjects (type I deficiency) and between 12 and 100 percent in 8 others (type II deficiency). Thirteen pCD36‐negative individuals had risk factors for immunization, and 4 had anti‐CD36. Some had a history resembling posttransfusion purpura (n = 2), platelet transfusion refractoriness (n = 1), and recurrent miscarriage (n = 1). No correlation was found between immunization and the amount of mCD36. Anti‐CD36 from an immunized type II‐deficient woman reacted with monocytes from normal controls but not with monocytes from type I‐ or type II‐deficient individuals, and thus it is postulated that mCD36 could be structurally different in normal and type II CD36‐deficient individuals.
CONCLUSION: CD36 deficiency is frequent in sub‐Saharan Africans; development of anti‐CD36 can lead to serious complications in multiply transfused patients, such as those with sicke cell disease.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Angioimmunoblastic T-cell lymphoma (AITL) represents a distinct entity among peripheral T-cell lymphomas (PTCLs). The cellular origin of AITL remains unknown, although a possible derivation from ...follicular helper T cells (TFH) has been suggested based on the CD4/Bcl-6 phenotype. It has been recently shown that expression of CXCL13, a chemokine critically involved in B-cell migration into germinal centers, is characteristic of TFH cells, as compared with other T helper subsets. We compared CXCL13 expression in 29 AITLs, 20 PTCLs, unspecified, 10 anaplastic large cell lymphomas (ALCL), and 4 other PTCLs. We showed that CXCL13 is expressed by AITL (29 of 29, 100%) and a subset of PTCL, unspecified (6 of 20, 30%), which all showed borderline features with AITL, but in only 1 of 10 (10%) ALCLs, and 0 of 4 other PTCLs. Two-color immunostainings further showed that CXCL13 was found in the cytoplasm of atypical CD5-positive T cells that expressed CD10. We conclude that CXCL13 expression is a common characteristic of AITL, which can help to delineate the morphologic spectrum of the disease, and further supports its derivation from TFH cells. CXCL13 expression may also provide an additional useful tool for the diagnosis of AITL.
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