Thyroid autoimmunity in chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is an autoimmune process in some patients. An association between CU and autoimmune thyroid disease has also previously been proposed. Our group has identified functionally significant histamine-releasing autoantibodies in one subset of CU patients (subset 1), predicted by positive autologous intradermal serum tests and positive histamine release from donor basophil leucocytes in vitro. Sera from a second subset of patients (subset 2), all of whom had positive autologous intradermal serum tests, failed to release histamine from donor basophils. A final disease subset (subset 3) has no identifiable skin reactivity (negative autologous serum skin test) or in vitro histamine releasing activity. OBJECTIVES: In order to examine further the possible relationships between thyroid autoimmunity, thyroid dysfunction and CU, we have examined thyroid autoantibodies and thyroid-stimulating hormone (TSH) levels (an indirect measure of thyroid dysfunction) in the three CU subsets. PATIENTS/METHODS: We studied 182 patients (69% female), of whom 90 had a positive autologous intradermal serum test. RESULTS: Eighteen skin test-positive and four skin test-negative patients had thyroid microsomal antibodies (TMA). TSH outside the normal range was found in 13 skin test-positive and one skin test-negative patient. These findings represent clustering of TMA positivity [risk ratio (RR) 4.06, 95% confidence interval (CI) 1.56-10.6] and of abnormal thyroid function (RR 15.5, CI 2.07-11.6) among the skin test-positive patients. However, in the overall study group an elevated TSH was present in seven patients (3.8%, CI 1.6-7.8) comparable to the 5% expected prevalence in the community. Thyroglobulin antibodies (TGA) were present in two of 182 patients. CONCLUSIONS: There were significant differences between skin test-positive and skin test-negative patients with regard to autoimmune thyroid disease. Evidence for autoimmune thyroid disease and abnormal thyroid function was largely found among the skin test-positive patients, supporting the theory of an autoimmune aetiology in this group.

Antibodies to beta2-glycoprotein I: a potential marker for clinical features of antiphospholipid antibody syndrome in patients with systemic lupus erythematosus.

OBJECTIVE: To clarify risk factors for the development of clinical features of antiphospholipid syndrome (APS) in patients with anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). METHODS: We studied 65 SLE patients, all with positive IgG and/or IgM aCL. Patients were divided into 2 groups; I: 29 SLE patients with features of APS (SLE/APS) and II: 36 aCL positive SLE patients without any feature of APS (SLE/aCL). Serum samples were collected from our serum bank. Anti-beta2-glycoprotein I (anti-beta2-GPI) were tested by ELISA using irradiated plates in the absence of cardiolipin. Anti-dsDNA antibodies were tested by standard Farr assay. RESULTS: There were no major differences between SLE clinical manifestations in both groups. However, the frequency of IgG anti-beta2-GPI was markedly increased in SLE/APS (18/29, 62%) than in SLE/aCL (4/36, 11%) (chi-squared 18.6, p=0.0001). The levels of anti-dsDNA antibodies in the same samples were slightly lower in SLE/APS. CONCLUSION: Our data suggest that increased levels of IgG anti-beta2-GPI may be a specific feature of SLE/APS patients rather than reflecting a polyclonal B cell activation.

Value of immunologic testing in stroke patients. A prospective multicenter study.

BACKGROUND AND PURPOSE: The aims of this prospective and multicenter study were to determine the frequency of anticardiolipin and antinuclear antibodies in an unselected ischemic and hemorrhagic stroke population and to evaluate the clinical significance of these autoantibodies. METHODS: Over a 1-year period, we collected plasma from 481 consecutive patients with ischemic or hemorrhagic stroke attending four different hospitals. Blood (10 mL) was drawn from each subject into a citrated glass tube. Plasma was obtained immediately by centrifugation and was stored at -70 degrees C until use. Concentrations of IgM and IgG anticardiolipin antibodies were measured at room temperature in normal (not heat-treated) plasma by standardized enzyme-linked immunosorbent assay. All sera were treated by indirect immunofluorescence on mouse liver and kidney sections for antinuclear antibodies. RESULTS: A total of 481 patients (325 men, 156 women) 16 to 90 years in age (mean age, 61 years) were studied. Anticardiolipin antibodies were present in 5 of 481 (1.04%) patients. One patient was IgG positive and four patients were IgM positive. Of 481 patients, 35 (7.2%) were positive for antinuclear antibodies. Anti-DNA antibodies were not demonstrable in any patient. CONCLUSIONS: The frequency of anticardiolipin antibodies in a heterogeneous stroke population is possibly lower than reported. The routine screening of anticardiolipin and antinuclear antibodies in a stroke population is of questionable value.

Isotype profile and clinical relevance of anticardiolipin antibodies in Sjögren's syndrome.

The purpose of this study was to determine the occurrence and clinical value of anticardiolipin antibodies in patients with Sjögren's syndrome. Thirty one patients with primary Sjögren's syndrome (all women, mean (SD) age 48.3 (11.2) years) and 32 patients with secondary Sjögren's syndrome with rheumatoid arthritis (all women, mean (SD) age 54.9 (11) years) were studied. IgG, IgM, and IgA anticardiolipin antibodies were determined by a standard enzyme linked immunosorbent assay (ELISA) technique. Anticardiolipin antibodies were found in five patients (16%) with primary Sjögren's syndrome and in seven patients (22%) with secondary Sjögren's syndrome. There was no correlation between anticardiolipin antibodies and the clinical features of the antiphospholipid syndrome (thrombotic events, fetal loss, thrombocytopenia) or extraglandular manifestations of Sjögren's syndrome (arthritis, skin lesions, myositis, polyneuropathy, central nervous system disease, pulmonary and renal disease) in either group. Among the various serological features studied, anticardiolipin antibodies correlated with antinuclear antibodies and antibodies to RNP only in patients with primary Sjögren's syndrome. These results indicate that although anticardiolipin antibodies are often found in serum samples from patients with Sjögren's syndrome, their clinical significance remains unclear.

Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis.

Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.

Cell lines of novel type derived from a diabetic secrete tissue-reactive human monoclonal antibodies.

Human monoclonal antibodies have been produced from lymphocytes of an acute-onset insulin-dependent diabetic patient. Peripheral blood lymphocytes were hybridized with a fusion partner HMY-1320. Initial screening of human immunoglobulin secretion was made by a nitrocellulose dot blot assay. Ten stable cell lines of novel type, secreting human immunoglobulin, were obtained. These cell lines have been maintained in continuous culture over 6 months and cryopreserved in liquid nitrogen for 14 months. Human monoclonal antibodies of IgG and IgM class have been produced and are secreted at a rate of 150-650 ng/ml/10(6) cells/day. Monoclonal antibodies were tested for histological staining against a variety of endocrine and non-endocrine tissues. One monoclonal antibody, LT1E12, demonstrates a staining pattern in human, rat, and mouse tissues, similar to that of mitochondrial antibodies. Another antibody, LT3C4, demonstrates weak staining of smooth muscle in rat and mouse kidney sections. Neither specificities were detected in the diabetic patient's serum. The variety of immune tissue specificities obtained in this study demonstrates the potential value of human monoclonal antibodies as probes to analyze the complexity of autoimmunity in diabetes mellitus.

Autoantibodies to cartilage and type II collagen in relapsing polychondritis and other rheumatic diseases.

Cartilage antibodies were demonstrated by indirect immunofluorescence (IFL) on human fetal cartilage in 6 out of 9 patients with relapsing polychondritis (RPC), in 4 out of 260 patients with rheumatoid arthritis (RA), and in only 1 out of 1016 patients with other disorders. The antibodies were specific for cartilage and evenly stained the whole cartilage matrix. They were predominantly of IgG class and varied in titres from 1:1 to 1:320. Follow-up studies in the RPC patients indicated that higher titres were present during the early acute phase of the disease. Five of the 6 positive cases had developed the disease within the past 12 months, and the 3 negative cases had had the disease for 3 to 7 years when tested. The RA cases showing positive cartilage IFL had no clinical evidence of RPC. Sequential measurements in 2 of the 4 cases showed that these antibodies became detectable some years after the onset of arthritis. Absorption studies with human type II collagen and purified porcine proteoglycan failed to remove the cartilage IFL. Antibodies to human native type II collagen were measured by an enzyme-linked immunosorbent assay. The highest levels were found in the RA sera which also displayed cartilage IFL, but the 2 tests gave discordant results. RPC sera showed the same antibody levels by this method, as did cartilage-IFL-negative RA sera, though both groups had higher mean levels than health controls. The findings that cartilage antibodies are detected in the majority of cases of RPC and only rarely in other diseases suggests these antibodies may play an important role in the pathogenesis of cartilage destruction in RPC.

A human-specific mitochondrial antibody its importance in the identification of organ-specific reactions.

A previously unrecognized autoantibody, detected by immunofluorescence, reacted with all human organs but gave negative results on tissues from rat, mouse, rabbit, guinea-pig, calf and chicken. From its predilection for mitochondria-rich cells (oncocytes) and its selective absorption with human but not animal mitochondria, it was identified as an anti-human mitochondrial antibody and named AHMA. The antibody is found in about 1% of normal subjects and is mostly of IgG class and of low titres. Its prevalence is increased in primary biliary cirrhosis where it may be associated with the standard non-species-specific AMA used for the differential diagnosis of this disease. The importance of AHMA is mainly in possible confusion with organ-specific reactions in submaxillary duct, parathyroid oxyphil cells and in trying to identify new endocrine cells such as those producing pancreatic polypeptide (HPP) in human tissues. Animals immunized with human hormones develop reactions to human mitochondria and thus produce misleading immunofluorescence reactions when used in low dilutions.