Biomedical subjects

Pierre Rohrlich

Publications and source records attributed to Pierre Rohrlich.

5 recordsLinked to original sources

PubMed2005

Use of real-time PCR to process the first galactomannan-positive serum sample in diagnosing invasive aspergillosis.

Positive galactomannan (GM) anti-genemias are included as a microbiological item in the diagnosis of probable or possible invasive aspergillosis (IA). Because false-positive GM results frequently occur, at least two positive results on two different samples are required. Waiting for clinical specimens can delay the initiation of treatment. As an alternative, we wondered whether detection of circulating Aspergillus DNA on the first positive GM serum sample could aid in diagnosing IA. Therefore, we retrospectively screened the first GM-positive serum samples from 29 patients from our hematology unit for Aspergillus DNA using real-time PCR. We compared the real-time PCR results with the final classification of proven, probable, and possible IA according to consensual criteria. No clear correlation between PCR results and the classification with the medical files could be shown. However, a positive PCR result was associated with a poor prognosis (Fisher's test; P=0.01). Our preliminary data suggest that a positive PCR result could indicate a more advanced stage of the disease. Therefore, concomitant positive PCR and GM results may justify the initiation of antifungal therapy in neutropenic patients. In contrast, a negative PCR on the first positive GM sample may argue for postponing costly antifungal administration until additional arguments for the diagnosis of IA are presented.

Adolescent↗

PubMed2004

The non-classical HLA class I molecule HFE does not influence the NK-like activity contained in fresh human PBMCs and does not interact with NK cells.

In humans, four beta2-microglobulin-associated non-classical class I molecules are encoded in the MHC: HLA-E, -F, -G and -H. Three of them (HLA-E, -F and -G) were shown to inhibit NK activity. On the contrary, the fourth one, HLA-H, named HFE after it was found to be mutated in patients suffering from inherited hemochromatosis, has been shown to be involved only in the regulation of iron uptake. We tested the capacity of HFE to affect (enhance or reduce) specifically the NK activity contained in non-manipulated fresh human PBMCs. We showed that HFE expression by target cells does not affect their killing by the NK-like activity contained in PBMCs. Moreover, using fluorescent HFE tetramers, we could confirm that blood NK cells as well as blood gammadelta T cells do not bind HFE. Altogether, our data indicate that HFE does not affect the NK activity contained in the PBMCs.

Animals↗

PubMed2003

Characterization of antigen-specific repertoire diversity following in vitro restimulation by a recombinant adenovirus expressing human cytomegalovirus pp65.

Human cytomegalovirus (HCMV) and adenovirus cause significant morbidity and mortality in immunocompromised hosts undergoing allogeneic stem cell transplantation. We have previously established a procedure for the generation of polyclonal CTL with specificity against adenovirus and HCMV using a recombinant adenovirus encoding the HCMV pp65 protein (RAdpp65). However, specific CTL expanded after in vitro culture steps were subjected to several in vitro restimulations and, depending on the protocol adopted, this could lead to a selection bias, compromising the clinical benefit. To determine which part of the memory repertoire is selected after in vitro restimulation, we have followed the specificity and clonal composition of pp65-peptide-specific CD8(+) T cells in HLA-A*201 individuals before and after repeated in vitro restimulation of cells with RAdpp65, combining HLA tetrameric complexes and immunoscope analysis. Tetramer staining showed that, after in vitro restimulation, up to 60% of CD8(+) T cells were virus-specific. Immunoscope analysis showed that the predominant TCRBV diversity of pp65-specific clones was conserved, demonstrating that the memory repertoire was preserved all along the procedure. Altogether, these results suggest that the use of RAdpp65 to induce CMV- and adenovirus-specific CTL maybe appropriate for immunotherapy.

Adenoviridae↗

PubMed2002

Increased hepatic iron in mice lacking classical MHC class I molecules.

Iron accumulation in the liver in hereditary hemochromatosis (HH) has been shown to be highly variable. Some studies point to the importance of major histocompatibility complex (MHC) class I (MHC-I) and CD8(+) cells as modifiers of iron overload. In this report, using mice knockout for H2K(b-/-) and H2D(b-/-) genes, it is demonstrated that lack of classical MHC-I molecules results in a spontaneous increase of nonheme iron content in the liver (mainly located in the hepatocytes) when compared to wild-type mice. In CD8(-/-) and Rag2(-/-) mice, no spontaneous hepatic iron accumulation was observed. These results demonstrate for the first time that classical MHC-I molecules could be involved in the regulation of iron metabolism and contribute to the established genotype/phenotype discrepancies seen in HH.

Animals↗

PubMed2002

Severe autoimmune hemolytic anemia caused by a warm IgA autoantibody directed against the third loop of band 3 (RBC anion-exchange protein 1).

BACKGROUND: Autoimmune hemolytic anemia associated with only IgA autoantibodies reacting optimally at 37 degrees C (WAIHA) is exceedingly rare. When identified, warm IgA autoantibodies specificities are usually directed to antigens of the Rh system. However, like IgG autoantibodies, the specificity of the majority of these antibodies is not identified. CASE REPORT: A case of a 3-year-old boy in whom a life-threatening IgA WAIHA occurred suddenly is reported. Following initial RBC transfusions and treatment with steroids at a dose of 3 mg per kg, which was slowly tapered, stabilization to a state of compensated hemolysis was achieved, persisting 4 months before complete resolution. There was no recurrence within a 16-month follow-up. STUDY DESIGN AND METHODS: The standard DAT in a gel column method with anti-IgG and anticomplement reagents was negative. However, the same method with an anti-IgA was strongly positive. RESULTS: The serum and the eluate obtained after acid elution reacted with all normal RBCs tested. Enzymatic treatment of panel RBCs by alpha-chymotrypsin and pronase abolished the reactivity. The reaction was completely inhibited by RBC incubation with four different MoAbs directed against the third extracellular loop of band 3, the RBC anion-exchange protein 1 (AE1), whereas MoAbs against other specificities showed no effect. CONCLUSIONS: This is the first report of an IgA autoantibody directed against the band 3 (AE1) protein and, more specifically, against the third loop. Moreover, this case underlines the importance of including IgA research in the initial diagnostic evaluation when a hemolytic anemia is suspected to be autoimmune and when IgG and complement are not detected on the patient's RBCs.

Agglutination Tests↗