L. Prin

IgG reactivity against citrullinated myelin basic protein in multiple sclerosis.

An increased level of citrullinated myelin basic protein (MBP-C8) has been reported in the brains of multiple sclerosis (MS) patients. However, the involvement of the immune response to post-translational modified MBP in the pathophysiology of MS remains speculative. The aim of this study was to compare the levels of immunoglobulin G antibodies to several MBP epitopes, before and after citrullination, in the cerebrospinal fluid (CSF) and sera of MS patients using enzyme-linked immunosorbent assay (ELISA). We analyzed antibody reactivity against various MBP-peptides in the CSF and sera of 60 MS patients, and 30 patients with other neurological diseases (OND) as controls. The peptides tested were: MBP(75-98) (peptide 1), native (peptide 2) and citrullinated (peptide 3) MBP(108-126) (ARG(122)-->Cit(122)), and native (peptide 4) and citrullinated (peptide 5) MBP(151-170) (ARG(159, 170)-->Cit(159, 170)). All selected peptides could support an immune reactivity in CSF and sera of MS and OND patients. A higher reactivity against peptide 4 was found in the CSF of MS patients compared with OND patients (P<0.0001), but not against citrullinated peptides (peptides 3 and 5). However, we observed that the citrullination state of peptide 2 modified the patterns of immune reactivity more markedly in MS patients (P<0.0001) than in OND patients (P<0.02). Although some MBP epitopes could be a potential target in MS, our data did not demonstrate any difference of antibody response to MBP peptides in their citrullinated forms.

CD3−CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder

The CD3−CD4+ lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3−CD4+ T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3−CD4+ lymphoid variant of hypereosinophilic syndrome. Atypical CD4+ T cells lymphoid infiltrates were found in 10 of 12 CD3−CD4+ L-HES patients, in lymph nodes (n=4 of 4 patients), in skin (n=9 of 9) and other extra-nodal tissues (gut, lacrymal gland, synovium). Lymph nodes displayed infiltrates limited to the interfollicular areas or even an effacement of nodal architecture, associated with proliferation of arborizing high endothelial venules and increased follicular dendritic cell meshwork. Analysis of 2 fresh skin samples confirmed the presence of CD3−CD4+ T cells. Clonal T cells were detected in at least one tissue in 8 patients, including lymph nodes (n=4 of 4): the same clonal T cells were detected in blood and in at least one biopsy, with a maximum delay of 23 years between samples. In the majority of cases, circulating CD3−CD4+ T cells were CD2hi (n=9 of 14), CD5hi (n=12 of 14), and CD7−(n=4 of 14) or CD7low (n=10 of 14). Angio-immunoblastic T-cell lymphoma can also present with CD3−CD4+ T cells; despite other common histopathological and immunophenotypic features, CD10 expression and follicular helper T-cell markers were not detected in lymphoid variant of hypereosinophilic syndrome patients, except in both patients who developed angio-immunoblastic T-cell lymphoma, and only at T-cell lymphoma diagnosis. Taken together, persistence of tissular clonal T cells and histopathological features define CD3−CD4+ lymphoid variant of hypereosinophilic syndrome as a peripheral indolent clonal T-cell lymphoproliferative disorder, which should not be confused with angio-immunoblastic T-cell lymphoma.

Traitement des hyperéosinophilies

Points essentiels Le choix de la conduite therapeutique devant une hypereosinophilie sanguine est lie a la cause sous-jacente. Une relation de cause a effet est parfois clairement etablie (parasitose) ou plus hypothetique (maladie systemique). Le traitement soit de la cause de l’hypereosinophilie , soit de la maladie associee a l’hypereosinophilie permet frequemment de normaliser le taux des eosinophiles circulants. La demarche est plus delicate lorsque son origine est totalement inconnue (hypereosinophilie chronique inexpliquee). Des protocoles varies ont fait preuve d’une certaine efficacite (corticoides, hydroxyuree, interferon α). Des approches plus rationnelles peuvent etre adoptees grâce a l’identification de nouveaux marqueurs cellulaires et moleculaires a signification diagnostique et physiopathologique.

Le polynucléaire éosinophile : nouveautés en physiologie et implications diagnostiques

Resume Le polynucleaire eosinophile (PNE) a ete un leucocyte longtemps neglige. On lui reconnait maintenant un large spectre de fonctions contrastees. Il peut etre, a la fois, une cellule effectrice ou une cellule regulatrice impliquee lors des phases de progression ou de resolution de la reponse inflammatoire. Il peut donc exprimer des proprietes benefiques ou nefastes pour l’hote. L’essentiel de ces donnees a ete acquis grâce a l’etude de contextes pathologiques particuliers ou dominent l’allergie et les parasitoses. Son impact dans d’autres affections et surtout sur certains processus homeostatiques suscite maintenant un interet croissant. Malgre le developpement de methodes d’analyses performantes, la definition precise du role physiopathologique du PNE est souvent delicate dans un contexte pathologique donne. Ces dernieres annees, la caracterisation de certains mecanismes de regulation de l’eosinophilie sanguine et tissulaire a ete un des elements novateurs les plus feconds. Il en est de meme pour l’appreciation de son implication dans la reponse immunitaire innee et adaptative. Ces aspects, abordes dans le premier chapitre de cette revue (nouveautes en physiologie), nous permettront de presenter dans la deuxieme partie (implications diagnostiques), une classification « physiopathologique » des hyper eosinophilies (HEs) et d’insister particulierement sur le fait qu’aucune HE ne doit etre negligee. Ces differentes contributions presentent l’avantage d’assurer aujourd’hui une prise en charge diagnostique et therapeutique plus adaptee des patients.

Interferon beta in multiple sclerosis: relationship between sustained serum IgG levels and clinical outcome.

We investigated the effects of interferon beta-1a (IFN beta-1a) on specific response towards two immunodominant MBP peptides and on global production of IgG. We evaluated 54 sera from multiple sclerosis (MS) patients at baseline and 1 year after treatment. We did not observe any modification of immune response to the MBP peptides but we noted a significant decrease in mean IgG concentrations in patients with progression of the disease but not in stable patients. These results suggest that IFN beta1a restores or maintains a beneficial immune response.