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E R Popa

Publications and source records attributed to E R Popa.

9 recordsLinked to original sources
PubMed2003

Staphylococcal superantigens and T cell expansions in Wegener's granulomatosis.

In Wegener's granulomatosis (WG), a form of autoimmune systemic vasculitis, chronic carriage of Staphylococcus aureus constitutes a risk factor for the development of exacerbations. Circulating T cells in this disease are persistently activated, suggesting the presence of a chronic stimulus. A causal link between chronic carriage of S. aureus and chronic T cell activation in WG is conceivable, because S. aureus produces superantigens (SAg), which are potent T cell stimulators. Superantigenic stimulation of T cells results in expansion of T cell subsets expressing SAg-binding T cell receptor V-beta (Vbeta) chains. In the present study we hypothesized that in WG the presence of staphylococcal SAg is accompanied by expansion of SAg-reacting T cell subsets. We tested our hypothesis in a cross-sectional and a longitudinal study in which the association between seven staphylococcal SAg genes [typed by poplymerase chain reaction (PCR)], eight SAg-binding Vbeta chains and four SAg-non-binding Vbeta chains (assessed by flow-cytometry) was assessed. Both studies showed that T cell expansions were present at a significantly higher rate in WG patients than in healthy individuals, but were not associated with the presence of either S. aureus or its SAg. Moreover, T cell expansions were generally of small extent, and did not appear simultaneously in both CD4 and CD8 subsets. We conclude that in WG S. aureus effects its supposed pathogenic function by a mechanism other than superantigenic T cell activation.

Adult↗
PubMed2003

The relation between Staphylococcus aureus and Wegener's granulomatosis: current knowledge and future directions.

To date, in the investigation of the role of S. aureus in WG, we face a paradoxical situation. On the one hand, clinical results obtained from treatment of WG patients with co-trimoxazole and studies assessing the impact of S. aureus on disease relapses strongly suggest that this bacterium contributes to disease pathophysiology. On the other hand, laboratory investigation of the possible mechanisms by which S. aureus is involved in WG is scarce, despite the fact that knowledge and tools to study this microorganism are abundant. In the present review, we discuss recent works investigating the possible pathophysiologic contribution of S. aureus to WG. Moreover, we propose a number of possibly relevant pathways of interaction of this bacterium with lymphoid and nonlymphoid cells of the WG host.

Anti-Infective Agents↗
PubMed2002

In vitro cytokine production and proliferation of T cells from patients with anti-proteinase 3- and antimyeloperoxidase-associated vasculitis, in response to proteinase 3 and myeloperoxidase.

OBJECTIVE: To investigate in vitro proliferative responses of CD4+ T cells and generation of specific cytokines induced by stimulation of peripheral blood mononuclear cells (PBMCs) from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with the autoantigens proteinase 3 (PR3) and myeloperoxidase (MPO). METHODS: PBMCs from vasculitis patients with PR3 ANCA or MPO ANCA and from healthy controls were stimulated for 7 days with PR3, MPO, or control stimuli. Proliferation of CD4+ T cells was assessed by flow cytometry, using the proliferation marker Ki-67. Levels of the pro-proliferative cytokines interleukin-2 (IL-2) and IL-6 and of the Th1 and Th2 cytokines interferon-gamma (IFN gamma) and IL-10 in culture supernatants were determined. RESULTS: PR3 and MPO induced proliferative responses in CD4+ T cells from individual patients with ANCA-associated vasculitides and healthy controls in vitro. Neither PR3 nor MPO elicited significant IL-2 production. Levels of IL-6 were highest after stimulation with PR3 but low after stimulation with MPO, independent of study group. Stimulation with PR3, and to a lesser extent with MPO, induced a Th2 cytokine milieu, characterized by high production of IL-6 and IL-10 and low production of IFN gamma in patients and controls. CONCLUSION: PR3 and MPO promote proliferation of CD4+ T cells from patients with ANCA-associated vasculitides, but also cross-stimulate T cells from healthy individuals. Strong IL-10 production elicited by PR3 in vitro may act as an inhibitory signal for T cell proliferation and may have an important immunoregulatory function in vivo.

Adult↗
PubMed2001

Origin of neointimal endothelium and alpha-actin-positive smooth muscle cells in transplant arteriosclerosis.

The development of transplant arteriosclerosis (TA) is today's most important problem in clinical organ transplantation. Histologically, TA is characterized by perivascular inflammation and progressive intimal thickening. Current thought on this process of vascular remodeling assumes that neointimal vascular smooth muscle (VSM) cells and endothelium in TA are graft-derived, holding that medial VSM cells proliferate and migrate into the subendothelial space in response to signals from inflammatory cells and damaged graft endothelium. Using MHC class I haplotype-specific immunohistochemical staining and single-cell PCR analyses, we show that the neointimal alpha-actin-positive VSM cells in rat aortic or cardiac allografts are of recipient and not of donor origin. In aortic but not in cardiac allografts, recipient-derived endothelial cells (ECs) replaced donor endothelium. Cyclosporine treatment prevents neointima formation and preserves the vascular media in aortic allografts. Recipient-derived ECs do not replace graft endothelium after cyclosporine treatment. We propose that, although it progresses beyond the needs of functional repair, TA reflects the activity of a normal healing process that restores vascular wall function following allograft-induced immunological injury.

Actins↗
PubMed2000

Most marginal zone B cells in rat express germline encoded Ig VH genes and are ligand selected.

The present study was performed to analyze whether marginal zone B (MZ-B) cells in nondeliberately immunized adult rats are selected on basis of the specificity of their B cell receptor, and to determine to what extent memory B cells contribute to the MZ-B cell subset. To this end, the Ig PC7183 V(H) gene repertoire was studied among V(H)DJ(H)-mu transcripts expressed in four sequential stages of B cell development, of two individual untreated adult rats. B cell subsets, i.e., pro/pre-B cells and newly formed B (NF-B) cells from bone marrow, and recirculating follicular B cells and MZ-B cells from spleen were sorted by flow cytometry. In addition, from one these rats, cells were microdissected from follicular and MZ areas of the spleen and productive PC7183 V(H) gene rearrangements were analyzed for the presence of somatic mutations. Sequence analysis reveals that most MZ-B cells in the adult rat, either defined by flow cytometry or by their anatomical location in the spleen, express germline encoded V(H) genes (naive MZ-B cells) and a minor fraction (about 20%) of the MZ-B cells carry somatic mutations (memory MZ-B cells). In addition, we show that naive MZ-B cells are a selected population of cells, both based on PC7183 V(H) gene repertoire and on the length of the Ig heavy (H) chain complementarity-determining region 3 (H-CDR3) region, i.e., PC7183 V(H)DJ(H)-mu transcripts of MZ-B cells carry significantly shorter H-CDR3 regions than other B cell subsets.

Amino Acid Sequence↗
PubMed2000

Recipient origin of neointimal vascular smooth muscle cells in cardiac allografts with transplant arteriosclerosis.

BACKGROUND: Coronary artery disease is today's most important post-heart transplantation problem after the first perioperative year. Histologically, coronary artery disease is characterized by transplant arteriosclerosis. The current view on this vasculopathy is that vascular smooth muscle (VSM) cells from the media of affected arteries proliferate and migrate into the sub-endothelial space (intima) in response to signals from inflammatory cells and damaged graft endothelium. According to this model, the intimal VSM cells in transplant arteriosclerotic lesions should originate from donor tissue. Using recipient-specific polymerase chain reaction (PCR) analysis of microdissected, single, neointimal VSM nuclei, we recently showed that after allogeneic aorta transplantation the neointimal VSM cells are of recipient and not of donor origin. In this study, we analyzed whether VSM-cell replacement with recipient-derived cells also takes place after allogeneic heart transplantation. METHODS: Cardiac allografts, when transplanted from female donors to male immune-modulated recipient rats, eventually developed transplant arteriosclerosis. We microdissected alpha-actin positive neointimal VSM cells from tissue sections and determined the origin (donor or recipient) using recipient-specific (male), single-cell, PCR analysis. RESULTS: In total, we analyzed 35 VSM-cell nuclei from 3 allografts, and PCR analysis revealed that 30/35 (86%) of the samples displayed the male-specific 128 base pair DNA fragment. These results indicate that after allogeneic cardiac transplantation, at least 86% of VSM cells in transplant arteriosclerotic lesions are of recipient origin. CONCLUSIONS: In contrast to current thought, the neointimal VSM cells in cardiac allografts that show transplant arteriosclerosis are of recipient and not of donor origin.

Actins↗
PubMed1999

Differential B- and T-cell activation in Wegener's granulomatosis.

BACKGROUND: Autoimmune mechanisms are postulated to play a role in the development and progression of Wegener's granulomatosis (WG), a form of systemic, idiopathic necrotizing vasculitis. OBJECTIVE: We investigated the relation between lymphocyte activation and disease activity in patients with WG. METHODS: B- and T-lymphocyte activation was studied by cytometric assessment of the expression of the activation markers CD38 on B cells and CD25 and HLA-DR on CD4(+) and CD8(+) T-cell subsets, respectively. Activation at the cellular level was related to serum levels of antineutrophil cytoplasmic antibodies and soluble IL-2 receptor, which can be regarded as soluble activation markers of B and T cells. RESULTS: Percentages of CD38(bright) activated B cells were higher in patients with active WG than in patients experiencing disease remission (P <.05) or in healthy control subjects (P <.05). Percentages of activated CD4(+) and CD8(+) T cells were higher in patients with active WG (CD4 subset, P <.0001; CD8 subset, P <.005) than in healthy individuals. An increased percentage of activated T cells of both subsets was also seen in patients whose condition was in remission, as compared with healthy control subjects (CD4 subset, P <.0005; CD8 subset, P <. 001). Lymphocyte activation at the cellular level did not correlate with plasma levels of antineutrophil cytoplasmic antibodies or soluble IL-2 receptor. CONCLUSION: In WG, B-cell activation is related to active disease, whereas T-cell activation persists during remission of the disease, which points to an intrinsic disordered immune system in this disease.

Adult↗
PubMed1999

The role of superantigens in vasculitis.

Multiple risk factors are involved in susceptibility to vasculitis. Inherited determinants may increase the risk but are insufficient to induce the disease. Environmental factors, such as infections, are important modulators and probably trigger the disease in most cases. One of the possible triggers may be a bacterial superantigen (SAg). SAgs may activate autoreactive T cells that mediate autoimmune vessel wall destruction. Furthermore, SAgs may activate autoreactive B cells to produce autoantibodies that are involved in the pathophysiology of vasculitis, such as antineutrophil cytoplasmic autoantibodies or anti-endothelial cell antibodies. In patients with Kawasaki disease, Wegener's granulomatosis, and infection-related forms of vasculitis, SAg-producing microorganisms have regularly been found. Activation of circulating T cells and skewing of the T-cell repertoire have been reported in most forms of vasculitis. In the past year, for the first time, patients were described in which T-cell receptor V beta expansions were documented simultaneously with the typing of the microbial SAgs, providing evidence that the observed changes in the T-cell repertoire could be caused by these bacterial SAgs. In the future, elucidation of the immunologic mechanisms by which SAgs may play a role in the pathophysiology of vasculitis will provide more effective methods for the treatment of vasculitis.

Antigens, Bacterial↗