bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serological association of lupus autoantibodies to a limited functional domain of 28S ribosomal RNA and to the ribosomal proteins bound to the domain
Authors: SATO T , UCHIUMI T , ARAKAWA M , KOMINAMI R 
Published: July 2010

SUMMARYSite-specific anti-RNA antibodies were sought in 120 sera of patients with autoimmune diseases by ribonuclease-protection assay using six fragments covering 28S ribosomal RNA (rRNA) as antigens. Fifteen of 90 sera from patients with systemic lupus erythematosus (SLE), but none of 30 sera of the other autoimmune diseases, provided a 60 nucleotide fragment within a region termed the ‘GTPase domain’ of 28S rRNA. These sera had potency to precipitate 0·42–69·3 nmol of the RNA domain per ml serum, which was higher than 15 control sera of healthy donors. No other specific antigenic site was detected in 28S rRNA under conditions used. All of the 15 sera having this anti-RNA antibody showed reactivity to ribosomal P proteins (anti-P), and two of them contained an additional antibody to ribosomal protein L12. These results suggested a strong association of the production of these three antibodies. Since P and L12 proteins form a stable complex with the GTPase domain, this serological association may result from an immune response to epitopes clustered on a single RNA-protein complex domain in ribosomes.
Evaluation of a model for post-partum arthritis and the role of oestrogen in prevention of MRL-lprassociated rheumatic conditions
Authors: RATKAY L G , ZHANG D , TONZETICH J , LEVY J G , WATERFIELD J D 
Published: July 2010

SUMMARYSixty-eight percent of female MRL-lpr- mice developed a post-partum exacerbation of their mild spontaneous arthritis within 30 days of parturition- The flare became evident between 5 and 15 days after delivery. Histologically it was characterized by a significant increase of subsynovial inflammation and synovial hyperplasia without changes in the level of cartilage and bone erosion. Immunohistologically, marked subsynovial and frequent synovial staining of MHC class II bearing cells was noted, along with the sporadic presence of CD3, CD4, and CD43 receptor-bearing cells in the subsynovium. Injection of physiological levels (0·08mg/kg) of estradiol on days 2, 3, 9, 15 and 20 post-partum delayed and reduced the flare to 23% of the animals. Administration of pharmacological amounts (0·4mg/kg per day for 2 weeks following Freund's complete adjuvant injection) prevented adjuvant-enhanced arthritis, reducing the incidence from 67% to the baseline 21% level- Deleterious changes in the underlying systemic lupus erythematosus (SLE), as demonstrated by proteinurea and mortality rate increases, were elicited only by the employed pharmacological amounts of estradiol. These results indicate that the MRL-lpr mice might serve as a model for post-partum flare of arthritis in SLE and rheumatoid arthritis by providing an approach to study the complexity of the effects of pregnancy on autoimmune diseases, and to obtain further evidence for the involvement of oestrogen in arthritis.
Use of methyl prednisolone and antioxidants in mercuric chloride-induced experimental vasculitis
Authors: QASIM F J , MATHIESON P W , THIRU S , OLIVEIRA D B G 
Published: July 2010

SUMMARYThe systemic vasculitides are characterized by necrotizing inflammation of blood vessels. Neutrophils are implicated in tissue damage by their presence at the site of injury. They can mediate injury by release of cellular contents including proteinases, cytokines and reactive oxygen species. Antioxidants such as vitamin E and N-acetyl cysteine (NAC) may therefore be predicted to ameliorate oxidative damage in vivo and could be a cheap and non-toxic form of therapy. We examined this hypothesis in an experimental model of vasculitis which has some similarities to human disease, and in which depletion of neutrophils ameliorates tissue injury. Mercuric chloride (HgCl2) treatment induces an autoimmune syndrome and necrotizing leucocytoclastic vasculitis in the Brown Norway (BN) rat; anti-myeloperoxidase (MPO) and anti-glomerular basement (GBM) antibodies are present, and vasculitis is reduced by antimicrobials. Methyl prednisolone given intravenously was effective in reducing tissue injury, demonstrating that the model was responsive to a treatment used in man. Vitamin E and NAC were given as daily injections intraperitoneally to BN rats either before, during or after HgCl2 administration. Serial blood samples were taken for anti-MPO and IgE antibodies, which were assayed by ELISA. Necropsies were performed on animals killed at peak disease. At doses of 50—200mg/kg per day vitamin E had no beneficial effect on tissue injury, regardless of timing of treatment, NAC at 100 or 200 mg/kg also had no significant protective effect on vasculitis. Autoantibody and IgE levels were not affected by either methyl prednisolone or the antioxidants. The lack of benefit of vitamin E and NAC suggests that oxidative damage, whether generated by neutrophils or other cells, does not play a major role in the pathogenesis of vasculitis, and that antioxidant therapy is unlikely to be of benefit in systemic vasculitis in man.
Predominance of T cell receptor Vδ3 in small bowel biopsies from celiac disease patients
Authors: FALK M C , NG G , ZHANG G Y , FANNING G C , KAMATH K R , KNIGHT J F 
Published: July 2010

SUMMARYIncreased numbers of T cells bearing the γδ antigen receptor (γδ T cells) have been reported in small bowel biopsies of patients with latent, active or treated coeliac disease. We have studied jejunal biopsies from seven children with coeliac disease and 10 children with normal gut histology to characterize γδ T cell receptor (TCR) variable region gene subfamily expression in resident γδ T cells and compared the results with the findings in peripheral blood mononuclear cells (PBMC) obtained on the same day as the gut biopsy. Molecular analysis of RNA extracted from PBMC and biopsies was performed by reverse transcription and amplification with the polymerase chain reaction using primers specific for six TCR Vδ families and four TCR Vγ families. We report, first, that a significantly increased number of γδ T cells expressing the TCR Vδ3 subfamily (P= 0·008) was observed in jejunal biopsies from children with coeliac disease, and second, that γδ T cell V region subfamily populations in gut differed from those seen in PBMC for both control and celiac patients. Significantly reduced numbers of TCR Vδ2, Vδ3, Vδ5 (P &lt; 0·01) and Vγ2, Vγ4 (P &lt; 0·01) T cells were found in gut compared with PBMC. The difference in γδ T cell repertoire observed between gut and blood may reflect differences in the nature of the antigens usually encountered in these two compartments. The over-representation of TCR Vδ3 in patients with coeliac disease suggests a specific role for these cells in the induction or maintenance of the jejunal abnormality associated with this disease.
Methotrexate treatment in murine experimental systemic lupus erythematosus (SLE); clinical benefits associated with cytokine manipulation
Authors: SEGAL R , DAYAN M , ZINGER H , MOZES E 
Published: July 2010

SUMMARYThe objective of this study was to determine the effects of Methotrexate (MTX) on the development and the course of experimental murine SLE, as well as on the cytokine profile involved in the disease. SLE was induced in naive BALB/c female mice by injection of the human anti-DNA MoAb bearing a common idiotype (16/6 Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with MTX (2 mg/kg once a week) for a period of 10 months. MTX treatment had no effect on 16/6 Id-induced autoantibody production. However, MTX treatment had beneficial effects on the clinical manifestations of the experimental disease (i.e. leucocyte counts, levels of protein in the urine and immune complex deposits in the kidneys). Thus, only 20% of 16/6 Id-immunized BALB/c mice that were treated with MTX had immune complex deposits in their kidneys compared with 100% of SLE-afflicted BALB/c mice that were not treated. We have observed a significant elevation in IL-1, tumour necrosis factor (TNF) and IL-10 secretion in BALB/c mice afflicted with experimental SLE. IL-2, IL-4, IL-6 and interferon-gamma (INF-γ) levels were decreased in these mice compared with the levels detected in healthy controls. Treatment with MTX reversed the levels of all the above cytokines to normal levels observed in control mice. These studies demonstrate therapeutic effects of MTX on murine experimental SLE. The normal cytokine profile observed following treatment with MTX is suggested to play a role in the amelioration of the clinical manifestations of experimental SLE.
Decreased cervicovaginal production of both IgA1 and IgA2 subclasses in women with AIDS
Authors: BELEC L , MEILLET D , GAILLARD O , PRAZUCK T , MICHEL E , EKOME J NGONDI , PILLOT J 
Published: July 2010

SUMMARYPaired sera and cervicovaginal secretions from 35 HIV-1-infected women representing different CDC stages of HIV infection were evaluated for total IgA, IgA1 and IgA2, for IgA, IgA1 and IgA2 to gp160, and for albumin. Age-matched healthy women (n= 45) served as controls. The secretion rates of total IgA, IgA1 and IgA2 were evaluated by calculating their relative coefficients of excretion by reference to albumin. In HIV-infected women, total IgA1 and IgA2 in sera and in cervicovaginal secretions increased proportionately as early as stages II + III and more markedly at stage IV. By contrast, the secretion rates of total IgA, IgA1 and IgA2 were markedly reduced in AIDS women, the IgA2 secretion rate decreasing significantly as early as stages II +III. This apparent discrepancy was probably the result of increased transudation of serum-borne immunoglobulins into the vaginal cavity, since albumin levels in cervicovaginal secretions increased significantly according to the stages of disease. HIV-reactive IgA antibodies in serum, as in cervicovaginal secretions, were principally found within the IgA 1 subclass. In women at stage IV, a high local production of IgA1 to gp160 occurred in spite of the impairment of cervicovaginal IgA synthesis, probably because of marked genital HIV replication at advanced stages.
Enhanced expression of MHC class I molecules on cultured human thyroid follicular cells infected with reovirus through induction of type 1 interferons
Authors: ATTA M S , IRVING W L , POWELL R J , TODD I 
Published: July 2010

SUMMARYCertain viruses are known to modulate the cellular expression of MHC molecules. We have investigated whether reovirus types 1 or 3 can alter the normal MHC molecule expression on cultured human thyroid follicular cells (TFC). Primary TFC cultures were established from eight human thyroid donors and MHC class I and II expression was assessed by indirect immunofluorescence microscopy. Both types of reovirus enhanced MHC class I expression on TFC from all thyroid donors. Class II MHC protein was strongly induced by type 1 reovirus on TFC from one donor, while weak induction of expression, by either reo-1 or reo-3 virus, was noted on the TFC of five other donors. Studies on the mechanism(s) of MHC class I hyperexpression showed that mouse MoAb against the type 3 reovirus haemagglutinin (anti-HA3) reduced the ability of the virus to induce hyperexpression of class I MHC molecules on TFC. However, supernatant harvested from type 3 reovirus-infected TFC cultures maintained its ability to enhance class I expression after incubation with anti-HA3. Moreover, adding rabbit anti-sera lo interferon-alpha (IFN-α) or IFN-β inhibited the increased class I MHC expression on TFC by both types of reovirus. These data suggest that reoviruses (types 1 and 3) can enhance MHC class I on cultured TFC. The mechanism of MHC class I enhancement is most probably through the release of IFN-α and IFN-β.
Activation of the endothelium by IL-1α and glucocorticoids results in major increase of complement C3 and factor B production and generation of C3a
Authors: COULPIER M , ANDREEV S , LEMERCIER C , DAUCHEL H , LEES O , FONTAINE M , RIPOCHE J 
Published: July 2010

SUMMARYConstitutive secretion of complement C3 and factor B by the endothelial cell (EC) is lowered by therapeutic concentrations of glucocorticoids such as hydrocortisone or dexamethasone, whereas regulatory protein factor H production is increased by these hormones. In contrast, the pro-inflammatory cytokine IL-1α has a stimulatory effect on C3 and factor B secretion by the endothelium and an inhibitory effect on factor H secretion. In this study, we examined the combined effect of IL-1α and glucocorticoids on C3 and factor B expression by the endothelial cell. When dexamethasone or hydrocortisone were added to IL-1α, significant potentialization of IL-1α-induced stimulation of C3 and factor B production was observed, occurring at various concentrations of either stimuli. Dose-response experiments indicate that, in vitro, optimal concentrations are in the range of 10−7 to 10−5m for dexamethasone and 50–200 U for IL-1α. In contrast, dexamethasone counteracts, in an additive way, the inhibitory effect of IL-1α on regulatory complement protein factor H production by EC. Such a potentialization between glucocorticoids and IL-1α was not observed for another marker of endothelial activation, IL-1α-induced stimulation of coagulation tissue factor expression. The association of glucocorticoids and IL-1α therefore appears to be a specific and major stimulus for the secretion of complement C3 and factor B, two acute-phase proteins, by the endothelium. As a result of the in vitro endothelium stimulation by glucocorticoids and IL-1α, C3a is generated in the vicinity of the endothelial cell. This study further suggests that complement activation, with its deleterious consequences, may result from the stimulation of endothelium in situations where high levels of IL-1α and endogenous glucocorticoids coexist, such as in septic shock.
Allergen-stimulated T lymphocytes from allergic patients induce vascular cell adhesion molecule-1 (VCAM-1) expression and IL-6 production by endothelial cells
Authors: DELNESTE Y , JEANNIN P , GOSSET P , LASSALLE P , CARDOT E , TILLIE-LEBLOND I , JOSEPH M , PESTEL J , TONNEL A-B 
Published: July 2010

SUMMARYAdhesion of inflammatory cells to endothelium is a critical step for their transvascular migration to inflammatory sites. To evaluate the relationship between T lymphocytes (TL) and vascular endothelium, supernatants from allergen-stimulated TL obtained from patients sensitive to Dermatophagoides pteronyssinus (Dpt) versus healthy subjects were added to endothelial cell (EC) cultures. TL were stimulated by autologous-activated antigen-presenting cells (APC) previously fixed in paraformaldehyde to prevent monokine secretion. Two parameters were measured: the expression of adhesion molecule and the production of IL-6. Related allergen-stimulated TL supernatants from allergic patients induced an increase of VCAM-1 and inter-cellular adhesion molecule-1 (ICAM-1) expression when supernatants of the control groups (TL exposed to an unrelated allergen or not stimulated or TL obtained from healthy subjects) did not, E-selectin expression was not modulated whatever the supernatant added to EC culture. IL-6 production by EC was significantly enhanced after activation with related allergen-stimulated TL supernatants from allergies compared with control supernatants. Induction of VCAM-1 expression was inhibited by adding neutralizing antibodies against IL-4, whereas IL-6 production and ICAM-I expression were inhibited by anti-interferon-gamma (IFN-γ) antibodies. Enhanced production of IL-4 and IFN-γ was detected in related allergen-stimulated TL supernatants from allergic subjects compared with the different supernatants. These data suggest that allergen-specific TL present in the peripheral blood of allergic patients are of Th1 and Th2 subtypes. Their stimulation in allergic patients may lead to the activation of endothelial cells and thereby participate in leucocyte recruitment towards the inflammatory site.
Antimycobacterial hsp65 and rheumatoid factor titres in a population of normal twins: evidence of genetic control of rheumatoid factor
Authors: Birnie D , Mckay I C , Veitch J , Whaley K , Hood S , Hillis W S , Holme E R 
Published: July 2010

SUMMARYRheumatoid arthritis (RA) is an autoimmune disease and rheumatoid factor (RF), anti-IgG, has been implicated in the pathogenesis, but the exact etiology remains unclear. There are data to suggest an infectious trigger to the autoimmune process, and mycobacteria are considered a candidate. Immunization of various animals with mycobacterial heat shock protein 65 (mhsp65) protects against subsequent autoimmune arthritis in a number of experimental models. Elevated anti-mhsp65 titres have been demonstrated in RA patients, together with specific T cells isolated from inflamed synovium. Mycobacterial hsp65 has also been implicated in other autoimmune disease and in atherosclerosis. The anti-mhsp65 and RF (IgG, IgM and IgA isotypes) titres were assayed by ELISA in 123 pairs of normal twins (61 monozygotic and 62 dizygotic, age 14–79 years), to examine the population distribution and inter-relationship of these antibodies. In addition, we studied the effects of age, sex, genetics and environment on antibody titres, IgG-RF and IgM-RF were detectable in all subjects and IgA-RF in 41 subjects. None of the RF isotypes showed any significant dependence on age or sex. There was a statistically significant correlation between twins for the IgG-RF and IgM-RF, and a positive but not significant correlation for the IgA-RF. All three correlations were stronger for monozygotic than dizygotic twins, reaching statistical significance for IgM-RF (P &lt; 0.001), and this indicates that there is a genetic influence on RF titres. Anti-mhsp65 titres were detectable in 90.5% of the study group with a range of 0.15–19.7 AU/ml. There were weak correlations between twins, stronger for dizygotic than monozygotic twins. This suggests that familial influences on anti-mhsp65 titres are very small, with no evidence of any genetic influence at all. There was no significant relationship of anti-mhsp65 titre with age, sex or RF titres.
Antigen-specific B cells present cartilage proteoglycan (aggrecan) to an autoreactive T cell hybridoma derived from a mouse with proteoglycan-induced arthritis
Authors: Brennan F R , Mikecz K , BuzÁS E I , Ragasa D , Cs-SzabÓ G , Negroiu G , Glant T T 
Published: July 2010

SUMMARYCartilage proteoglycan (aggrecan)-induced polyarthritis in BALB/c mice is characterized by chronic inflammation and destruction of joint tissues similar to that observed in human rheumatoid arthritis. The immunization of mice with fetal human proteoglycan (PG) elicits specific antibodies to the immunizing antigen of which a population cross-reacts with native mouse PG. This (auto)antibody production is immediately followed by an explosive proliferation of autoreactive T cells, suggesting that PG-specific B cells may participate in antigen presentation of PG to autoreactive T cells. We therefore isolated B cells from the spleens and lymph nodes of PG-immunized mice and examined their ability to present PG to a PG-specific T cell hybridoma. The antigen-specific T cell responses elicited by B cells from PG-immunized mice (both arthritic and clinically asymptomatic) were markedly higher that those of non-immune mice and keyhole limpet haemocyanin (KLH)-immunized mice, and these B cells could present low PG concentrations. Levels of B cell presentation corresponded with the serum levels of PG-specific antibodies, implying that these B cells were presenting the PG specifically via their surface immunoglobulin. This B cell T cell interaction was strongly dependent on MHC class II/T cell receptor (TCR), LFA-1/intercellular adhesion molecule-1 (ICAM-1) and CD28/B7 interactions, as antibodies to Ia, ICAM-1 and B7-2 (but not to B7-1) markedly reduced presentation. These data indicate that PG-specific B cells may play an essential role in governing the development of PG-induced arthritis.
The outer surface proteins of Lyme disease borrelia spirochetes stimulate T cells to secrete interferon-gamma (IFN-γ): diagnostic and pathogenic implications
Authors: Forsberg P , Ernerudh J , Ekerfelt C , Roberg M , Vrethem M , BergstrÖM S 
Published: July 2010

SUMMARYLate stages of borrelia Lyme disease infections may be difficult to diagnose because of unspecific symptoms and unreliable laboratory tests, being too unspecific or insensitive. The T cell immune response was thus evaluated in these patients by using a sensitive ELISPOT T cell assay that detects the secretion of IFN-γ, i.e. a T helper 1 (Th1) response on the single-cell level. Three subcellular fractions of the Lyme borreliosis strain Borrelia afzelii were used for antigenic stimulation. The outer surface protein (Osp) fraction elicited the strongest response, discriminating between borrelia infections (n= 15) compared with other neurological diseases (n= 10) and normal controls (n= 12) (P= 0.0001). The more heterogeneous sonicated borrelia fraction also elicited a strong response, however, also in some of the controls. The flagellin fraction did not have a similar T cell-stimulating effect. When looking at subgroups of borrelia infections, central nervous system (CNS) infections (n= 7) revealed a lower T cell response in blood (P= 0.0128) compared with other borrelia manifestations (n= 8). Cerebrospinal fluid (CSF) lymphocytes were available from three patients with CNS borreliosis, and all showed a compartmentalization with higher responses to the Osp fraction in CSF compared with blood, also in the two patients without any intrathecal-specific antibody synthesis. The ELISPOT method is feasible for detecting a specific IFN-γ T cell response in borrelia infections. This Th1 response may well be of pathogenic relevance.
Reduced antigen-presenting function of human Epstein-Barr virus (EBV)-B cells and monocytes after UVB radiation is accompanied by decreased expression of B7, intercellular adhesion molecule-1 (ICAM-1) and LFA-3
Authors: Kremer I B , Bos J D , Teunissen M B M 
Published: July 2010

SUMMARYIn this study, the effect of ultraviolet-B (UVB) radiation on antigen-presenting function was studied, to investigate whether antigen-presenting cells (APC) are inhibited by UVB through a common mechanism. Two types of human APC were used: EBV-B cells and monocytes, and these were irradiated in vitro with single low doses of UVB (range 0–200 J/m2). Irradiation of EBV-B cells or monocytes resulted in similar dose-dependent reduction in APC function, when determined by the allogeneic mixed leucocyte reaction (MLR) or Candida albicans- or tetanus toxoid-specific T cell response. Our study shows that the reduced APC function was not likely to be caused by alterations in antigen processing or cytokine production. However, UVB-irradiated APC displayed marked changes in adhesion molecule expression. Irradiated EBV-B cells showed reduced expression of ICAM-1 (30%), LFA-3 (25%) and B7-1 (35%), white expression of HLA-DR, CD19 and LFA-1 was not affected. UVB irradiation of monocytes did result in reduction in the expression of HLA-DR (30%), LFA-3 (40%), ICAM-1 (65%) and B7-1 and B7-3 (90%), but had no effect on CD14, LFA-1 and ICAM-3 expression. Addition of non-irradiated cells (but not the supernatant of these cells) or CD28 antibodies partly restored T cell activation, indicating that UVB-induced reduction in APC function is at least partly mediated via impairment of co-stimulatory molecule expression.