Assessment of intracranial vessels in association with carotid atherosclerosis and brain vascular lesions in rheumatoid arthritis

BACKGROUND: Stroke has been associated with rheumatoid arthritis (RA). We assessed patients with RA and healthy control subjects by transcranial Doppler (TCD), carotid ultrasonography and brain magnetic resonance imaging (MRI). METHODS: Altogether, 41 female patients with RA undergoing methotrexate (MTX) or biologic treatment and 60 age-matched control subjects underwent TCD assessment of the middle cerebral artery (MCA) and basilar artery. Pulsatility index (PI), resistivity (resistance) index (RI) and circulatory reserve capacity (CRC) were determined at rest (r) and after apnoea (a) and hyperventilation (h). The presence of carotid plaques and carotid intima-media thickness (cIMT) were also determined. Intracerebral vascular lesions were investigated by brain MRI. RESULTS: MCA PI and RI values at rest and after apnoea were significantly increased in the total and MTX-treated RA populations vs control subjects. MCA CRC was also impaired, and basilar artery PI was higher in RA. More patients with RA had carotid plaques and increased cIMT. Linear regression analysis revealed that left PI(r) and RI(r) correlated with disease duration and that left PI(r), RI(r), PI(a), PI(h) and basilar PI correlated with disease activity. Right CRC inversely correlated with 28-joint Disease Activity Score. Disease activity was an independent determinant of left PI(a) and right CRC. Compared with long-term MTX treatment alone, the use of biologics in combination with MTX was associated with less impaired cerebral circulation. Impaired cerebral circulation was also associated with measures of carotid atherosclerosis. CONCLUSIONS: To our knowledge, this is the first study to show increased distal MCA and basilar artery occlusion in RA as determined by TCD. Patients with RA also had CRC defects. We also confirmed increased carotid plaque formation and increased cIMT. Biologics may beneficially influence some parameters in the intracranial vessels

Mycoplasma Contamination Revisited: Mesenchymal Stromal Cells Harboring Mycoplasma hyorhinis Potently Inhibit Lymphocyte Proliferation In Vitro

Mesenchymal stromal cells (MSC) have important immunomodulatory effects that can be exploited in the clinical setting, e.g. in patients suffering from graft-versus-host disease after allogeneic stem cell transplantation. In an experimental animal model, cultures of rat T lymphocytes were stimulated in vitro either with the mitogen Concanavalin A or with irradiated allogeneic cells in mixed lymphocyte reactions, the latter to simulate allo-immunogenic activation of transplanted T cells in vivo. This study investigated the inhibitory effects of rat bone marrow-derived MSC subsequently found to be infected with a common mycoplasma species (Mycoplasma hyorhinis) on T cell activation in vitro and experimental graft-versus-host disease in vivo.We found that M. hyorhinis infection increased the anti-proliferative effect of MSC dramatically, as measured by both radiometric and fluorimetric methods. Inhibition could not be explained solely by the well-known ability of mycoplasmas to degrade tritiated thymidine, but likely was the result of rapid dissemination of M. hyorhinis in the lymphocyte culture.This study demonstrates the potent inhibitory effect exerted by M. hyorhinis in standard lymphocyte proliferation assays in vitro. MSC are efficient vectors of mycoplasma infection, emphasizing the importance of monitoring cell cultures for contamination

IgE epitope analysis of the hevein preprotein; a major latex allergen

We have previously identified the hevein preprotein as a common allergen for latex allergic healthcare workers. The B cell epitopes in the hevein protein that are recognized by IgE of latex-allergic individuals have not been identified. In this study, we examined the hevein preprotein using epitope mapping. Overlapping synthetic peptides of 10 amino acids (two aa overlap) were synthesized on a derivatized cellulose membrane using Fmoc chemistry. The peptide spots were probed with pooled sera from 10 latex-allergic patients, and the IgE-reactive peptides identified with anti-IgE MoAbs. We identified six B cell epitopes within the full length hevein preprotein which bound IgE from latex-allergic patients. Two were located in the N-terminal 5-kD hevein domain and four were observed in the 14-kD C-domain. A broad epitope was located between the N-terminal amino acids 13–24. This epitope had nearly complete homology to wheat germ agglutinin (WGA). Immunological cross-reactivity to WGA was confirmed by Western blot analysis with purified WGA, and this reactivity could be inhibited by latex proteins or WGA. Of the five remaining epitopes, four had homologies to other proteins in the pathogenesis-related family of plant proteins (PR-4). The data demonstrate that hevein has multiple IgE epitopes. The significant homology of these epitopes to a broad family of plant defence proteins further explains the increased prevalence of food allergies in latex-allergic individuals

Lipid transfer protein from Hevea brasiliensis (Hev b 12), a cross-reactive latex protein

BACKGROUND: Latex-allergic individuals experience clinical cross-reactivity to a large number of fruits and vegetables. Much of the cross-reactivity can be attributed to Hev b 6, but evidence indicates that additional cross-reactive allergens may be present. A common pan-allergen, which has not previously been identified in latex, but may contribute to this cross-reactivity is lipid transfer protein (LTP). We sought to determine whether Hevea brasiliensis produces LTP and whether it would bind immunoglobulin E from latex-allergic patients. METHODS: LTP was identified in H. brasiliensis RNA by polymerase chain reaction using degenerate primers. The entire cDNA was obtained by polymerase chain reaction using rapid amplification of cDNA ends reactions. The complete coding sequence for LTP was determined and produced as a recombinant protein using the glutathione S-transferase and pET32 expression systems. Immunoblot analysis of sera from latex-allergic patients was used to determine whether patients recognize LTP as an allergen. RESULTS: We identified a 662-basepair cDNA with a 351-basepair open reading frame that encodes for a 116-amino acid protein. The protein has significant homology to the family of nonspecific LTPs. We expressed the protein as a mature LTP of 92 amino acids with a predicted isoelectric point of 10.8 and molecular weight of 9.3 kDa. Immunoblots demonstrated specific immunoglobulin E for LTP in the sera of 9 of 37 (24%) latex-allergic individuals. CONCLUSIONS: We describe the initial identification of rLTP in H. brasiliensis that may be important as a cross-reactive pan-allergen (Hev b 12

Are the Morphological Indices of the Vertebrobasilar System Heritable? A Twin Study Based on 3D Reconstructed Models

Background and Objectives: The asymmetrical vertebral artery (VA) flow and diameter are common findings, which can result in an asymmetrical blood flow in the basilar artery (BA), leading to bending of the artery over time. This study investigated whether the variation of the different vertebrobasilar morphological indices that influence flow characteristics might be inherited. Materials and Methods: We analyzed 200 cerebral magnetic resonance imaging (MRI) scans of healthy Caucasian twins (100 pairs) who underwent time-of-flight MRI. From the scans, we reconstructed the 3D mesh of the posterior circulation from the start of the V4 segment to the basilar tip and subsequently analyzed the morphology of the vertebrobasilar system. The phenotypic covariances of the different morphological parameters were decomposed into heritability (A), shared (C), and unshared (E) environmental effects. Results: 39% of the twins had left dominant VA, while 32.5% had right dominant. In addition, 28.5% were classified as equal. The vertebral artery V4 segment diameter, curvature, and tortuosity were mainly influenced by shared (C) and unshared (E) environmental factors. A moderate heritability was found for the BA length (A: 63%; 95% CI: 45.7–75.2%; E: 37%; 95% CI: 24.8–54.3%) and volume (A: 60.1%; 95% CI: 42.4–73.2%; E: 39.9%; 95% CI: 26.8–57.6%), while the torsion of both arteries showed no heritability and were only influenced by the unshared environment. Conclusions: The length and volume of the BA show a moderate genetical influence. However, most of the measured morphological indices were influenced by shared and unshared factors, which highlight the role of the ever-changing hemodynamic influences shaping the geometry of the vertebrobasilar system

Are the Morphological Indices of the Vertebrobasilar System Heritable? A Twin Study Based on 3D Reconstructed Models

Background and Objectives: The asymmetrical vertebral artery (VA) flow and diameter are common findings, which can result in an asymmetrical blood flow in the basilar artery (BA), leading to bending of the artery over time. This study investigated whether the variation of the different vertebrobasilar morphological indices that influence flow characteristics might be inherited. Materials and Methods: We analyzed 200 cerebral magnetic resonance imaging (MRI) scans of healthy Caucasian twins (100 pairs) who underwent time-of-flight MRI. From the scans, we reconstructed the 3D mesh of the posterior circulation from the start of the V4 segment to the basilar tip and subsequently analyzed the morphology of the vertebrobasilar system. The phenotypic covariances of the different morphological parameters were decomposed into heritability (A), shared (C), and unshared (E) environmental effects. Results: 39% of the twins had left dominant VA, while 32.5% had right dominant. In addition, 28.5% were classified as equal. The vertebral artery V4 segment diameter, curvature, and tortuosity were mainly influenced by shared (C) and unshared (E) environmental factors. A moderate heritability was found for the BA length (A: 63%; 95% CI: 45.7–75.2%; E: 37%; 95% CI: 24.8–54.3%) and volume (A: 60.1%; 95% CI: 42.4–73.2%; E: 39.9%; 95% CI: 26.8–57.6%), while the torsion of both arteries showed no heritability and were only influenced by the unshared environment. Conclusions: The length and volume of the BA show a moderate genetical influence. However, most of the measured morphological indices were influenced by shared and unshared factors, which highlight the role of the ever-changing hemodynamic influences shaping the geometry of the vertebrobasilar system