Rheumatoid Arthritis: Durand V

Durand V, Lamour A, Devauchelle V, Youinou P, Jamin C. · Laboratory of Immunology, Institut de Synergie des Sciences et de la Santé, Brest, France. · Clin Rev Allergy Immunol. · Pubmed #10907104 No free full text.

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Mamoune A, Durand V, Le Goff P, Pennec YL, Youinou P, Le Corre R. · Laboratory of Immunology, Brest University Medical School, France. · Histol Histopathol. · Pubmed #10809380 No free full text.

Abstract: CD45RO+ T cells are referred to as memory or helper-inducer while CD45RA+ T cells are regarded as naive or suppressor-inducer T cells. The former population predominates in the peripheral blood and even more in the synovial fluid of patients with rheumatoid arthritis, to the expense of the latter population. Within the CD45RB+ compartment, there appears to be more of the fully-differentiated than of the early-differentiated CD4+ T cells. In spite of the fact that these lymphocytes are close to undergoing apoptosis, this programmed cell death is inhibited in the rheumatoid synovium.

Durand V, Pers JO, Renaudineau Y, Saraux A, Youinou P, Jamin C. · Laboratory of Immunology, Institut de Synergie des Sciences et de la Santé, Brest University Medical School, France. · J Leukoc Biol. · Pubmed #11272273 links to  free full text

Abstract: Anti-Fc gamma receptor IIIb (Fc gammaRIIIb) human autoantibodies (Ab) have been classified previously into three groups, based on the results of an indirect immunofluorescence (IIF) test and an enzyme-linked immunosorbent assay (ELISA): IIF+/ELISA+ (group A), IIF+/ELISA- (group B), and IIF-/ELISA+ (group C) sera. In this study, differential effects between IIF+ autoAb, recognizing cell-bound Fc gammaR, and those ELISA+, recognizing only cell-free Fc gammaR, were studied on polymorphonuclear neutrophils (PMN). Neither group A nor B autoAb was cytotoxic, although both prolonged the survival of PMN by delaying spontaneous apoptosis. By the same extent, the PMN-binding antisera stimulated the appearance of a CD11b(dim) population, following a 12-h incubation. This event was associated with a lowered expression of beta2 integrin molecules, resulting in altered PMN function. Treatment with groups A and B autoAb reduced adhesiveness and respiratory burst. This impairment of the responses was more pronounced when the cells originated from donors NA1+ NA1+ rather than donors NA2+ NA2+. From our observations, the influences of anti-Fc gammaRIIIb autoAb on PMN survival, as well as function and subsequent dysregulation of the inflammatory response, have proven somewhat dependent on their target antigens, as determined by IIF coupled with ELISA and Fc gammaRIIIb polymorphism.

Bodman-Smith MD, Anand A, Durand V, Youinou PY, Lydyard PM. · Department of Immunology, Royal Free and University College London Medical School, London, UK. · Immunology. · Pubmed #10792496 links to  free full text

Abstract: Some gammadelta T cells express a receptor for the Fc portion of immunoglobulin G (FcgammaRIII - CD16). The relevance of this Fc receptor to gammadelta T-cell function is at present unclear. Our previous studies have shown that gammadelta T cells express activation markers in patients with rheumatoid arthritis (RA). In this study we have examined the relative proportions of CD16+ gammadelta T cells in the blood and synovial fluid of these patients compared with control blood. CD16+ gammadelta T cells from RA patients were significantly reduced in synovial fluid compared with the circulation. That this was due to blocking of antibody binding to CD16 was unlikely as treatment of blood gammadelta T cells with RA synovial fluid (known to contain immune complexes) failed to alter expression of CD16. Treatment of blood gammadelta T cells with phytohaemagglutinin in vitro, resulted in a time-dependent decrease in expression of CD16, with a concomitant increase in expression of human leucocyte antigen-DR, at the single cell level. We conclude that expression of CD16 by gammadelta T cells is lost in the synovial compartment as the result of activation.

Basset C, Durand V, Mimassi N, Pennec YL, Youinou P, Dueymes M. · Laboratory of Immunology; Department of Internal Medicine, Institut de Synergie des Sciences et de la Santé (I3S), Brest University Medical School, Brest, France. · Scand J Immunol. · Pubmed #10736101 No free full text.

Abstract: Despite the indisputable role of immunoglobulin (Ig)A in the pathogenesis of primary Sjögren syndrome (pSS), the causative abnormality remains largely unknown. As an extension of our report that IgA is oversialylated in this disease, the thrust of the present study was to measure the sialyltransferase (ST) activity in B lymphocytes. ST containing lysates of B cells from 17 pSS patients and 10 controls, were obtained using a combination of detergents, and incubated with affinity purified IgA that had been previously desialylated. The deposition of cytidine 5' monophosphate sialic acid (SA) by ST from B cells onto IgA was detected by two ELISA based upon the use of biotinylated lectins (Sambucus nigra agglutinin which is specific for alpha2-6 SA and Maackia amurensis which is specific for alpha2-3 SA). In parallel, the amount of SA on IgA from ten of the 17 patients and eight of the 10 controls was assayed using the same method. An excess of alpha2-3 and alpha2-6 SA on IgA was found in those patients with excessive activity of alpha2-3 and alpha2-6 ST. Thus, IgA hypersialylation in pSS patients may result from undue activity of ST.

Basset C, Durand V, Jamin C, Clément J, Pennec Y, Youinou P, Dueymes M, Roitt IM. · Laboratory of Immunology, Institut de Synergie des Sciences et de la Santé (I3S), Brest, France. · Scand J Immunol. · Pubmed #10736100 No free full text.

Abstract: Increased serum immunoglobulin A (IgA) level is a common finding in primary Sjögren's syndrome (pSS). IgA might not be properly eliminated because of an abnormal glycosylation. We reported previously that IgA1 from patients with pSS was oversialylated. We extend this finding by showing that monomeric IgA1 contains more sialic acid (SA) in patients than in controls, as determined by enzyme-linked immunosorbent assay (ELISA) and Western blot with Sambucus nigra agglutinin (SNA), a lectin specific for SA. To localize this excess of SA on the N- and/or O-linked oligosaccharides, we analysed them separately, using N- and O-linked oligosaccharide profiling kits based on fluorophore-assisted carbohydrate electrophoresis. N-linked, but not O-linked, oligosaccharides of patients' IgA1 were oversialylated, and this seemed to be linked to an excess of SA on the same number of polysaccharides as normal IgA1. To localize the abnormality to the Fab and/or Fc fragments, monomeric IgA1 was digested with protease, separated and transferred to nitrocellulose, where SA was identified by SNA. Both Fab and Fc fragments appeared to be oversialylated. Oversialylation of N-linked oligosaccharides of IgA1 from patients with pSS might prevent the recognition of IgA by receptors that are responsible for their clearance, resulting in an excess of serum IgA and related immune complexes.

Basset C, Devauchelle V, Durand V, Jamin C, Pennec YL, Youinou P, Dueymes M. · Brest University Medical School, Brest, France. · Scand J Immunol. · Pubmed #10607305 No free full text.

Abstract: Immunoglobulin A (IgA), which is heavily glycosylated, interacts with a variety of receptors, e.g. the asialoglycoprotein receptor (ASGP-R), which binds terminal galactose residues, and the Fcalpha receptor (FcalphaRI). It has thus been proposed that elevated serum levels of IgA in primary Sjögren's syndrome (pSS) are caused by its defective clearance. To test this hypothesis, we developed a method (based on sialyl transferases eluted from a hepatoma cell line) to increase the amount of sialic acid (SA) on IgA, and used a battery of IgA1- and IgA2-specific glycosidases to reduce this amount. Binding of IgA1 and IgA2 to ASGP-R and FcalphaRI was found to be sugar dependent because oversialylated IgA bound less than native or desialylated IgA. However, individual sugars did not play a direct role in this binding. Given that IgA are oversialylated in pSS, defective clearance of IgA may indeed be ascribed to an excess of SA in IgA1 and IgA2.