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1

B cell tolerance to self in systemic autoimmunity

100%
Zouali M.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 5
361-366
EN
After a century of research and despite intensive scrutiny, the origin of autoantibody production remains an enigma. Recently, the essential role of B cells in promoting systemic autoimmunity in mice seems more important than previously thought: self-reactive B cells can be subject to positive selection and a deficiency in serum IgM predisposes to the development of IgG antibodies to autoantigens. Studies of the B cell repertoire expressed in systemic autoimmune diseases have provided important clues. In human lupus, quantitation of this repertoire reveals the presence of an expansion of IgG clonotypes that impart reactivity with disease-related autoantigens. The nucleotide sequences of autoantibodies derived from these patients and expressing nephritogenic idiotopes (present in immune complexes and renal eluates of subjects with active disease) show features of diversification with a high rate of replacement/silent mutations and clustering of the mutations in the hypervariable regions, suggesting than an antigen-driven process plays a role in the generation of pathogenic autoantibodies. Currently, the contributions of apoptosis and of cell receptor signaling to this triggering are being appreciated. Pursuing these and related issues will have an important impact on autoimmune research.
2

Emerging concepts in the molecular pathogenesis of systemic lupus erythematosus

100%
Nambiar M. P., Juang Y.-T., Tsokos G. C.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
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issue 1
35-46
EN
Systemic lupus erythematosus is a prototypic autoimmune disease that predominantly afflicts women during child-bearing age. The disease is characterized by the production of autoantibodies and immune complexes in association with a diverse array of clinical manifestations. Investigation into the etiopathogenesis has been directed at identifying the genes that provide susceptibility to the disease, the complex cellular and cytokine aberrations and the biochemical abnormalities that are responsible for them. Understanding the immune cell signaling and gene transcription abnormalities will help us tailor new strategies for efficient biotherapy of the disease.
3

Vascular endothelial growth factor in systemic lupus erythematosus: relationship to disease activity, systemic organ manifestation, and nailfold capillaroscopic abnormalities

100%
Kuryliszyn-Moskal A., Klimiuk P. A., Sierakowski S., Ciolkiewicz M.
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2007
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vol. 55
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issue 3
179-185
EN
Introduction: The aim of the study was to evaluate whether vascular endothelial growth factor (VEGF) serum level is associated with systemic organ involvement, microvascular changes as determined by nailfold capillaroscopy, and disease activity of systemic lupus erythematosus (SLE). Materials and Methods: Serum levels of VEGF were determined by an enzyme-linked immunosorbent assay in 47 SLE patients and in 30 healthy controls. Nailfold capillaroscopy was performed in all patients and healthy subjects. Results: Morphological changes were observed by nailfold capillaroscopy in 45 of 47 (95.7%) SLE patients. Mild capillary changes were found in 16 (34%), moderate in 21 (44.7%), and severe in 8 (17%) SLE patients. All patients with systemic organ involvement showed severe or moderate changes in nailfold capillaroscopy. In comparison with the control group, a higher serum concentration of VEGF in SLE patients was demonstrated (p<0.05). Furthermore, significant differences in VEGF serum concentration between SLE patients with systemic involvement and controls were found (p<0.01). Comparison between patients with active and inactive SLE according to SLEDAI score showed a significantly higher concentration of VEGF in the sera of patients with active SLE (p<0.01). The SLE patients with severe and moderate changes in nailfold capillaroscopy showed significantly higher VEGF serum levels than SLE patients with mild changes (p<0.05) or healthy controls (p<0.01). Moreover, the VEGF serum level correlated significantly with ESR (r=0.580, p<0.0001) and CRP (r=0.512, p<0.005). Conclusions: Our data suggest that VEGF serum level may be a useful marker of disease activity and internal organ involvement in SLE patients. Abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with systemic manifestation in SLE. Abbreviations: SLE ? systemic lupus erythematosus, VEGF ? vascular endothelial growth factor, SSc ? systemic sclerosis, RA ? rheumatoid arthritis, CTD ? connective tissue disease, SLEDAI ? Systemic Lupus Erythematosus Disease Activity Index, HRCT ? high-resolution computed tomography, ESR ? erythrocyte sedimentation rate, CRP ? C-reactive protein.
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