Koussay Dellagi

Antivimentin Autoantibodies in Angioimmunoblastic Lymphadenopathy

We evaluated the prevalence and specificity of smooth-muscle autoantibodies in 20 serum samples obtained from patients with angioimmunoblastic lymphadenopathy. Smooth-muscle antibodies in high titers were detected in 75 per cent of the samples. No such antibodies were found in 30 normal control serum samples or in 10 samples from patients with non-Hodgkins lymphoma and 1 of 12 from patients with other types of polyclonal hypergammaglobulinemia were positive. The antibodies were polyclonal and belonged to the IgM, IgG, and IgA classes. They reacted with vimentin, the major polypeptide of the intermediate-filament cytoskeleton of mesenchymal cells. The pattern of tissue reactivity and absorption experiments both show that these antibodies recognize special antigenic determinants of the vimentin polypeptide that are shared by vimentin and other classes of intermediate-filament proteins - namely, keratin and desmin. The frequency of this unusual autoantibody activity in angioimmunoblastic lymphadenopathy suggests that, like hypergammaglobulinemia and a positive Coombs test, it may represent a useful serologic marker for the disease.

Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due to Leishmania major Infection in Four Inbred Mouse Strains

ABSATRCT Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials.

Cytogenetic assessment of Fanconi anemia in children with aplastic anemia in Tunisia.

Background: Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for Fanconi anemia (FA) diagnosis. The aim of the present study was to assess the proportion of FA cases among aplastic anemia (AA) in Tunisian pediatric patients. Observation: Investigation of mitomycin C-induced chromosomal breakage was carried out in 163 pediatric patients with AA and siblings of the cases where diagnosis of FA was confirmed. We identified 31 patients with FA whose percentage of unstable mitoses ranges from 65% to 100%. Among 18 siblings who were investigated for chromosomal instability, 3 were incidentally found to be affected. Conclusions: FA is an important cause of AA in Tunisia. Our report is the first study in North Africa that explored cytogenetic and phenotypic findings in FA children. It also showed the importance of mitomycin C sensitivity screening in all FA siblings.

Antibody activities of human monoclonal immunoglobulins

A number of antibody activities of human monoclonal immunoglobulins (Ig) have been described and knowledge in this field has progressed since we reviewed it 20 years ago (Seligmann and Brouet 1973). In this presentation, we wish to update the current findings and concepts, summarize our data on monoclonal autoantibodies to myelin-associated glycoprotein (MAG), and emphasize their relevance to the problem of the origin of autoantibodies.

INTERMEDIATE FILAMENTS OF NORMAL AND MALIGNANT HUMAN LYMPHOID CELLS AS STUDIED WITH HUMAN MONOCLONAL IgM WITH ANTIBODY ACTIVITY

ABSTRACT We determined the class of intermediate filaments (IF) of normal or malignant lymphoid cells using as probes two human monoclonal IgM with an autoantibody activity against IF. Normal and leukemic cells (including lymphoid precursors) expressed vimentin IF whereas a proportion of normal or malignant plasma cells had no detectable vimentin. In a second set of experiments we investigated the fate of IF during the capping of lymphocyte surface molecules and showed that IF were redistributed underneath the cap; this last finding may indicate a new role for IF.