Variety Of Systemic Autoimmune Diseases Research Articles

Silica, Apoptosis, and Autoimmunity

Relatively little is known regarding mechanisms of environmental exposures in the development of autoimmune disease. However, several environmental agents are implicated in triggering or accelerating systemic autoimmune disease, including mercury, iodine, vinyl chloride, certain pharmaceuticals, and crystalline silica. There is increasing epidemiological evidence supporting the hypothesis that occupational silica exposure is associated with a variety of systemic autoimmune diseases, including scleroderma (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), glomerulonephritis (GN) and small vessel vasculitis (SVV). However, there have been few mechanistic studies examining silica exposure and autoimmune disease initiation and progression. This review summarizes human epidemiology data linking silica exposure with systemic autoimmune disease, but focuses on possible mechanisms by which silica can lead to the development and progression of autoimmunity.

Characterization of anticytoplasmic antibodies in patients with systemic autoimmune diseases

We characterized the cytoplasmic staining patterns identified by indirect immunofluorescence (IF) using human epithelial (HEp-2) cells as substrates, and identified autoantigens using enzyme-linked immunosorbent assay (ELISA) and cognate RNA immunoprecipitation techniques in cytoplasmic antibody-positive sera (CA(+)) in patients with systemic autoimmune diseases. Twenty-three sera (3.7%) of 630 patients were found to have a cytoplasmic staining pattern by IF on HEp-2 cells. The fine-pattern IF specificities were as follows: 12 diffuse fine speckled; 7 coarse granular filamentous speckled; 2 diffuse coarse speckled; 1 condensed large speckled; 1 cytoskeletal. No relationship was found between the staining patterns and the diseases. Anti-SS-A antibodies and antimitochondrial (M2) antibodies were detected by ELISA in 6 and 4 sera, respectively, and antismooth muscle antibody was detected by IF in 1 serum. In RNA immunoprecipitation assays, 6, 11, 3, and 1 patients had antibodies that recognized aminoacyltransfer RNA (tRNA) synthetases (including 2 EJ, 2 PL-7, 1 PL-12, and 1 unidentified tRNA-related), SS-A, ribosomes, and SRP, respectively. Moreover, several other autoantigens were detected by Western blotting using human epithelial (HEp-2) cell lysates. This study suggests that autoantibodies against tRNA synthetases, SS-A, ribosomes, mitochondria, and other autoantigens are present in CA(+) sera from patients with a variety of systemic autoimmune diseases.

Characterization of anticytoplasmic antibodies in patients with systemic autoimmune diseases

We characterized the cytoplasmic staining patterns identified by indirect immunofluorescence (IF) using human epithelial (HEp-2) cells as substrates, and identified autoantigens using enzyme-linked immunosorbent assay (ELISA) and cognate RNA immunoprecipitation techniques in cytoplasmic antibody-positive sera (CA(+)) in patients with systemic autoimmune diseases. Twenty-three sera (3.7%) of 630 patients were found to have a cytoplasmic staining pattern by IF on HEp-2 cells. The fine-pattern IF specificities were as follows: 12 diffuse fine speckled; 7 coarse granular filamentous speckled; 2 diffuse coarse speckled; 1 condensed large speckled; 1 cytoskeletal. No relationship was found between the staining patterns and the diseases. Anti-SS-A antibodies and antimitochondrial (M2) antibodies were detected by ELISA in 6 and 4 sera, respectively, and antismooth muscle antibody was detected by IF in 1 serum. In RNA immunoprecipitation assays, 6, 11, 3, and 1 patients had antibodies that recognized aminoacyltransfer RNA (tRNA) synthetases (including 2 EJ, 2 PL-7, 1 PL-12, and 1 unidentified tRNA-related), SS-A, ribosomes, and SRP, respectively. Moreover, several other autoantigens were detected by Western blotting using human epithelial (HEp-2) cell lysates. This study suggests that autoantibodies against tRNA synthetases, SS-A, ribosomes, mitochondria, and other autoantigens are present in CA(+) sera from patients with a variety of systemic autoimmune diseases.

Evidence for aberrant regulation of the p21Ras pathway in PBMCs of patients with chronic idiopathic urticaria

Background: Recent data suggest that a subpopulation of patients with chronic urticaria has an autoimmune disorder. Aberrant expression and regulation of the p21Ras pathway has been reported in lymphoid cells in a variety of systemic autoimmune diseases but not in chronic idiopathic urticaria (CIU). Objectives: The aim of this study was to examine the expression, regulation, and function of the p21Ras pathway in patients with CIU. Methods: Twenty-four patients with CIU and 14 control subjects were enrolled. All patients and 9 control subjects were intradermally injected with autologous serum. PBMCs were isolated, and the p21Ras and its regulatory proteins were studied. Results: We found increased expression of the p21ras proto-oncogene in patients with CIU. This was associated with a low expression of the p21Ras stimulatory element human son of sevenless (hSOS1) but normally expressed p21Ras inhibitory element p120GTPase-activating protein. The basal nonstimulated membrane/cytoplasmic ratio of hSOS1, which indicates the p21Ras pathway activity, was higher in patients compared with that seen in control subjects. Moreover, after stimulation, both patients and control subjects decreased their hSOS1 membrane/cytoplasmic ratio. The magnitude of this decrease was much higher in patients than in control subjects: 14- and approximately 2-fold, respectively. The basal and stimulated activities of the p21Ras downstream key regulatory enzyme mitogen-activated protein kinase were comparable in patients and control subjects, as was their in vitro mitogen-stimulated lymphocyte proliferation. Conclusion: Our data demonstrate for the first time an aberrant signaling through the p21Ras pathway in lymphocytes of patients with CIU. This finding further supports the autoimmune basis of this disease. (J Allergy Clin Immunol 2002;109:349-56.)

Autoimmunity and Otologic Disease: Clinical and Experimental Aspects

Each of the anatomic structures of the ear (external, middle, and inner) is subject to immunologic influence and injury. Studies in experimental animals have shown that primary immune responses to foreign antigens can be induced within the middle and inner ear as indicated by (1) infiltration and local persistence of mononuclear leukocytes and plasma cells, (2) appearance of antibody in perilymph, and (3) eventual development of systemic immunity. Protective effects of inner ear immunization against subsequent viral challenge have also been shown. Clinically, otologic disease can occur in association with a wide variety of systemic autoimmune and immunologic disorders: systemic lupus erythematosus, rheumatoid arthritis, Behçet's disease, Sjögren's syndrome, relapsing polychondritis, ulcerative colitis, Cogan's syndrome, and vasculitis-related disease. Evidence for immunologic involvement has also been found in cases of idiopathic sensorineural hearing loss frequently accompanied by vestibular-dysfunction (Meniere's disease). Many of these cases progress into systemic autoimmune disorders. Autoimmune-associated hearing loss has been recognized as one of the few types of treatable hearing dysfunction, with good responses to immunosuppressive therapy. The pathogenesis of autoimmune-related otologic disease has not been established; however, evidence suggests three possible types of immunologic injury: (1) autoantibody binding to type II collagen or other otologic components (type II immunologic injury); (2) immune complex formation leading to vasculitis (type III); and (3) T cell-mediated autoreactivity to inner ear membranous elements (type IV). These mechanisms may not be mutually exclusive. Clinical laboratory procedures should be directed at evaluating these possibilities to assist in diagnosis.