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Biomedical subjects

Marie-Alexandra Alyanakian

Publications and source records attributed to Marie-Alexandra Alyanakian.

11 recordsLinked to original sources
PubMed2006

Monoclonal immunoglobulin with antitransferrin activity: A rare cause of hypersideremia with increased transferrin saturation.

Two unusual but similar cases of very high serum iron, extremely high transferrin concentrations (5.4 to 6.5 g/L), and increased transferrin saturation are reported. No anemia or microcytosis was observed. The ferritin concentration remained within the normal range, and no iron overload was observed. In one case, the in vivo half-life of 59Fe-labeled transferrin was shown to be prolonged (206 minutes versus 75 minutes for controls). In both patients, a monoclonal IgG was observed in the serum. The association between serum transferrin and monoclonal IgG was demonstrated by Western blot analysis and affinity chromatography. We suggest that the transferrin bound to the monoclonal IgG molecule has a prolonged half-life in the circulation, leading to high transferrin concentrations, and that the increased serum iron values prevent the onset of anemia. The antitransferrin activity of monoclonal antibody should be added to the list of situations accounting for elevated serum iron with elevated transferrin saturation.

Antibodies, Monoclonal↗
PubMed2006

Transforming growth factor-beta and T-cell-mediated immunoregulation in the control of autoimmune diabetes.

It is now well-established that CD4+ regulatory T cells are instrumental in controlling immune responses both to self-antigens and to non-self-antigens. However, the precise modalities involved in their differentiation and survival, their mode of action and their antigen specificity are only partially understood. We have been particularly interested in the study of regulatory T cells controlling autoimmune insulin-dependent diabetes. Here, we provide evidence to support the phenotypic and functional diversity of regulatory T cells mediating transferable 'active' or 'dominant' peripheral tolerance in the non-obese diabetic mouse model (NOD). They include natural and adaptive regulatory T cells that are operational both in unmanipulated NOD mice and in animals undergoing treatments aimed at inducing/restoring tolerance to self-beta-cell antigens. At least in our hands, the differential cytokine-dependency appears as a major distinctive feature of regulatory T cells subsets. Among immunoregulatory cytokines, transforming growth factor-beta(TGF-beta) appeared to play a key role. Herein we discuss these results and the working hypothesis they evoke in the context of the present literature, where the role of TGF-beta-dependent T-cell-mediated immunoregulation is still debated.

Animals↗
PubMed2006

Transforming growth factor-beta and natural killer T-cells are involved in the protective effect of a bacterial extract on type 1 diabetes.

The onset of type 1 diabetes in NOD mice is delayed by oral administration of a bacterial extract (OM-85) and can be completely prevented by its intraperitoneal administration. Optimal prevention is observed when starting treatment at 3 or 6 weeks of age, and some effect is still observed with treatment at 10 weeks of age. Using genetically deficient mice and cytokine-neutralizing monoclonal antibodies, we demonstrate here that the therapeutic effect does not involve T-helper type 2 cytokines (interleukin [IL]-4 and -10) but is tightly dependent on transforming growth factor (TGF)-beta. Natural killer T-cells also participate in the therapeutic effect because CD1d(-/-) NOD mice are partially resistant to the protective effect of OM-85. The question remains of the specificity of the protective effect of OM-85, which may include proinflammatory components. It will thus be important to further characterize the molecular components that afford protection from type 1 diabetes. Lipopolysaccharide is excluded, but other Toll-like receptor (TLR) agonists could be involved because OM-85 stimulated dendritic cells and induced TGF-beta production by splenocytes in a TLR-2-, TLR-4-, and MyD88-dependent fashion.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Type III cryoglobulinemia complicated by renal cortical necrosis.

Renal involvement is rare in patients with type III cryoglobulinemia. We report a case of renal cortical necrosis in a patient with type III cryoglobulinemia. Renal function improved partially after treatment with plasma exchange, steroids, and cyclophosphamide. Renal magnetic resonance imaging was a valuable tool in the evaluation of the extent of renal cortical necrosis and improvement in renal vascularization after treatment.

Arthritis, Rheumatoid↗
PubMed2005

Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells.

Diabetogenic T-cells can be detected in pre-diabetic nonobese diabetic (NOD) mice after transfer in NOD-SCID recipients. Here we demonstrate that 6-week-old pre-diabetic NOD mice, >2 months before disease onset, already harbor pathogenic T-cells in equal numbers to overtly diabetic animals. The delay in diabetes appearance is explained by the presence of regulatory CD4+ CD25+ T-cells that control diabetogenic effectors and that are, in our hands, transforming growth factor (TGF)-beta-dependent. Our present results suggest, however, that diabetes onset is only partly explained by a decline in this regulatory T-cell activity. Another major factor appears to be the progressive resistance of diabetogenic cells to TGF-beta-dependent mediated inhibition. We propose that progression to overt disease correlates with the pathogenic T-cell's escape from TGF-beta-dependent T-cell-mediated regulation.

Adoptive Transfer↗
PubMed2004

Prevalence of mixed cryoglobulins in relation to CD4 cell count among patients coinfected with HIV and hepatitis C virus.

Cryoglobulinemia was studied in human immunodeficiency virus-positive, hepatitis C virus (HCV)-positive patients in relation to their CD4 cell count. Cryoglobulinemia was found in 18 (31.6%) of 57 patients: 17 (44.7%) of 38 patients with a CD4 cell count of >or=200 cells/ micro L versus 1 (5.3%) of 19 patients with a CD4 cell count of <200 cells/ micro L (P=.0064). Cell-mediated immunity could, therefore, contribute to the production of HCV-associated cryoglobulins.

Adult↗
PubMed2004

Free immunoglobulin light-chain serum levels in the follow-up of patients with monoclonal gammopathies: correlation with 24-hr urinary light-chain excretion.

In patients with light-chain myeloma or primary AL-amyloidosis, 24-hr light-chain excretion in the urine is considered an essential marker of the tumor mass. However, 24-hr urine collection and analysis may be cumbersome and prone to inaccuracy. Recently, a sensitive immunonephelometric assay for immunoglobulin free light chains (FLC) in the serum was developed. We sought to determine whether the serum level of monoclonal FLC could be used as an indicator of urinary excretion and disease evolution. Seven patients with light-chain myeloma and AL-amyloidosis were studied, all of which had a monoclonal FLC that could be detected in the urine using standard methods. In four of these patients, follow-up revealed a remarkable correlation between FLC serum levels and daily urinary excretions. The ratio of serum level to urinary light-chain excretion, although stable in a given patient, was extremely variable between patients. In the three remaining cases featuring hardly measurable amounts of light chain in the urine, the serum FLC assay proved sensitive enough for correlation with clinical events. Thus, immunonephelometric measurement of serum FLCs is a reliable method for the follow-up of patients with light-chain secreting monoclonal gammopathies.

Follow-Up Studies↗
PubMed2003

Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseases.

Depletion of selected regulatory CD4+ T cell subsets induces the spontaneous onset of various immune or autoimmune disorders. It is not clear, however, whether a given subset, notably CD4+CD25+ regulatory T cells, protects from a wide spectrum of immune disorders, or whether specialized subsets of regulatory T cells control each given disease or group of diseases. We report here, using diabetes prone nonobese diabetic (NOD) mice, that depending on the regulatory T cells that are depleted, i.e., CD25+, CD62L+, or CD45RB(low), distinct immune diseases appear after transfer into NOD severe combined immunodeficiency (SCID) recipients. Thus, reconstitution of NOD SCID mice with CD25- T cells induces major gastritis and late-onset diabetes, but no or mild colitis. Reconstitution with CD62L- T cells induces fulminant diabetes with no colitis or gastritis. Reconstitution with CD45RB(high) T cells induces major colitis with wasting disease and no or very moderate gastritis and diabetes. Major differences among the three regulatory T cell subsets are also seen in vitro. The bulk of suppressor cells inhibiting the proliferation of CD4+CD25- T cells in coculture is concentrated within the CD25+ but not the CD62L+ or CD45RB(low) T cell subsets. Similarly, cytokine production patterns are significantly different for each regulatory T cell subset. Collectively, these data point to the diversity and organ selectivity of regulatory T cells controlling distinct autoimmune diseases whatever the underlying mechanisms.

Animals↗
PubMed2002

Renal involvement in monoclonal (type I) cryoglobulinemia: two cases associated with IgG3 kappa cryoglobulin.

Renal involvement has been described rarely in monoclonal (type I) cryoglobulinemia, although this complication is frequent among patients with mixed (type II or III) cryoglobulin. We report two patients with glomerulonephritis and monoclonal IgGkappa cryoglobulin. Both patients presented with nephrotic syndrome, microscopic hematuria, and impaired renal function. Hepatitis C serology was negative, bone marrow aspiration was normal, and the renal biopsy specimen showed membranoproliferative glomerulonephritis with glomerular subendothelial deposits of monoclonal IgGkappa. In both cases, circulating cryoglobulin and monotypic tissue deposits were found to be IgG3kappa, suggesting that this isotype may have a particular propensity to cause this type of membranoproliferative glomerulonephritis. Although 18 cases of type I cryoglobulinemia with biopsy-proven glomerulonephritis have been reported to date, this is the first characterization of immunoglobulin heavy-chain isotype in this disease.

Aged↗