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Biomedical subjects

C Betterle

Publications and source records attributed to C Betterle.

At least 73 records · Page 4Linked to original sources
PubMed1995

Follicular thyroid cells of autoimmune thyroiditis may coexpress ICAM-1 (CD54) and its natural ligand LFA-1 (CD11a/CD18).

The leukocyte functional associated antigen-1 (LFA-1)-intercellular adhesion molecule-1 (CD11a-CD18/CD54) intercellular adhesion system plays a crucial role in several immunologic phenomena, including adhesion between lymphocytes and epithelial cells. In previous studies evidence for CD54 expression on thyroid follicular cells in Hashimoto's thyroiditis was provided. In this study we evaluated the possible expression of CD11a and CD18 antigens on thyrocytes of patients with Hashimoto's thyroiditis and on thyrocytes of patients with Graves' disease and simple goiter as controls; we used both alkaline phosphatase immunostaining and indirect immunofluorescence on cryostatic tissue sections. The results showed that LFA-1 (both CD11a and CD18) positivity on thyroid follicles may occur in glands of patients with Hashimoto's disease, with a pattern very similar to that of CD54: this was observed in five of seven specimens. Conversely, no positivity was observed in tissues from patients with Graves' disease or goiter: notably, isolated follicular cells from Graves' goiter tissues are induced in culture to express CD54, but not LFA-1. Using double-staining techniques, we were able to show that in specimens from patients with Hashimoto's disease, the same follicular structures coexpressed LFA-1 and CD54. Such a coexpression of the two ligands further emphasizes the possible role of this adhesion system in the pathogenesis of epithelial damage, through bidirectional interactions between thyroid epithelial cells and infiltrating LFA-1 or CD54-positive mononuclear cells.

Adult↗
PubMed1995

Immunoprecipitation assay for autoantibodies to steroid 21-hydroxylase in autoimmune adrenal diseases.

Adrenal autoantibodies characteristic of autoimmune Addison disease are directed towards steroid 21-hydroxylase (21-OH; EC 1.14.99.10). We describe a new assay to measure 21-OH autoantibodies (21-OH Abs), based on immunoprecipitation by the antibodies of 35S-labeled human 21-OH. Using this immunoprecipitation assay (IPA), we detected 21-OH Abs in 42 of 64 (66%) patients with Addison disease and in 14 of 19 (74%) patients with autoimmune polyendocrine syndromes type I and type II. No 21-OH Abs were detected by the IPA in any patients with Addison disease attributable to tuberculosis (n = 9) or adrenoleukodystrophy (n = 9) or in patients with autoimmune thyroid disease (n = 28), systemic lupus erythematosus (n = 10), myasthenia gravis (n = 10), rheumatoid arthritis (n = 10), or insulin-dependent diabetes mellitus (n = 12). None of the 26 sera from healthy normal blood donors was positive for 21-OH Abs by the assay. We found good agreement between 21-OH Abs measured by IPA and by Western blotting (r = 0.83, n = 123, P < 0.001). The inter- and intraassay CVs for IPA were well < 10% at high, medium, and low concentrations of 21-OH Abs. Overall, our studies indicate that the IPA provides a specific, sensitive, and convenient system for measuring 21-OH Abs.

Addison Disease↗
PubMed1994

The natural history of pre-type 1 (insulin-dependent) diabetes mellitus in patients with autoimmune endocrine diseases.

An 11-year prospective study was carried out in 180 non-diabetic patients with organ-specific autoimmune diseases to evaluate islet cell antibodies in predicting Type 1 (insulin-dependent) diabetes mellitus. Islet cell antibodies were characterised according to titres, persistence, complement-fixing ability, and pattern. During follow-up, 14 of 46 patients with islet cell antibodies persistently greater than 5 Juvenile Diabetes Foundation Units (JDF-U) (30.4%), none of 23 with islet cell antibodies between 2.5 and 5 JDF-U or fluctuating, and 3 of 109 without islet cell antibodies (2.7%), developed diabetes. The cumulative risk of developing diabetes was 70%, 0%, and 4%, respectively. All the patients who developed diabetes were females. Eight progressed to insulin-dependence acutely, four showed a transient period of non-insulin-dependence, while two were still insulin-free. No difference was found in titres of islet cell antibodies for the risk of diabetes. Complement-fixing islet cell antibodies enhanced the cumulative risk for the disease in patients with conventional islet cell antibodies at low-middle (> or = 2.5-40 JDF-U), but not at high (> or = 80 JDF-U) titres. Forty-two patients with islet cell antibodies were investigated for the whole or the selective pattern. In the presence of the whole pattern the cumulative risk for diabetes rose to 100%, while with the selective pattern it declined to 34%. The whole pattern was found in 83% of patients who developed Type 1 diabetes acutely. In patients with organ-specific autoimmune diseases, the whole islet cell antibody pattern greatly enhances the prediction for diabetes.

Adolescent↗
PubMed1994

24-hour blood pressure profile in Addison's disease.

The purpose of this study was to evaluate the circadian blood pressure rhythmicity in patients with primary adrenal insufficiency. Ten newly diagnosed and untreated patients with Addison's disease, 17 addisonian patients (including the previous 10) following an adequate regimen of corticosteroid replacement therapy, and 15 healthy subjects as a control group were studied. Twenty-four-hour ambulatory blood pressure and heart rate were measured automatically every 30 min using a Takeda TM-2420 recorder. The runs test, used for detecting blood pressure diurnal rhythm, was compatible with a rhythm in 2 of 10 patients with untreated Addison's disease, in 13 of 17 patients with treated Addison's disease, and in 13 of 15 normals. Six of eight addisonian patients showing no evidence of blood pressure rhythm in the untreated state acquired circadian periodicity during therapy. An analysis of blood pressure readings by Fourier series with four harmonics showed that blood pressure mesor was lower in untreated than in treated addisonian and normal subjects (P < .05). The nocturnal fall was smaller for systolic and diastolic blood pressure in untreated than in treated addisonian and normal subjects (P < .05). Adrenocortical insufficiency is often characterized by loss of circadian blood pressure rhythm, and normal rhythm can be reestablished by replacement therapy. Lack of cortisol rhythm or persistent activation of the renin-angiotensin system and sympathetic tone may play a role in this phenomenon.

Addison Disease↗
PubMed1994

Early adrenal hypofunction in patients with organ-specific autoantibodies and no clinical adrenal insufficiency.

Idiopathic Addison's disease occurs frequently in association with other organ-specific autoimmune diseases, and autoantibodies to adrenal cortex are markers of this condition. A variable asymptomatic period with subtle adrenal dysfunction may precede the onset of clinical manifestations. We studied the pituitary-adrenal axis by measuring plasma ACTH, cortisol, and 17 alpha-hydroxyprogesterone after ovine CRH (100 micrograms as an iv bolus) stimulation in 19 patients with organ-specific autoimmune disease and adrenal autoantibodies, in whom adrenal steroids were normal under baseline conditions and normally responsive to a standard ACTH stimulation test (250 micrograms). In all subjects, oCRH produced a normal increase in plasma ACTH. Plasma cortisol, which was normoresponsive in 11 subjects, showed little or no increase in 8 subjects. Two of these patients developed overt adrenal failure after 1 yr. The 17 alpha-hydroxyprogesterone response to oCRH, tested in 10 of 19 patients, paralleled that of plasma cortisol, excluding a steroidogenic block at the 21-hydroxylase site. Our data demonstrate the existence of a very early phase of Addison's disease in which adrenal function shows an impaired response to ovine CRH-stimulated ACTH.

17-alpha-Hydroxyprogesterone↗
PubMed1994

Lack of immunohistological changes in the islets of nondiabetic, autoimmune, polyendocrine patients with beta-selective GAD-specific islet cell antibodies.

We examined the pancreases from three nondiabetic, autoimmune, polyendocrine patients with islet cell antibodies (ICAs) and glutamic acid decarboxylase (GAD) antibodies who died without developing insulin-dependent diabetes mellitus (IDDM). All three patients had the beta-selective GAD-specific ICA subtype and antibodies to the GAD-derived 50 kD tryptic fragment. None had whole islet ICA or antibodies to the non-GAD-derived 37k islet antigen, which appear to be more closely associated with IDDM than antibodies to GAD. The three patients also were negative for insulin autoantibodies. Islets within pancreas from patients 1 and 2 appeared well preserved as assessed by hematoxylin and eosin staining. In these two patients, insulin content, as assessed by indirect immunofluorescence on cryostat sections, was normal. Patient 3 had a prolonged postmortem time, and the islet insulin content was reduced slightly. In all three pancreases, no evidence was found of increased human leukocyte antigen class I or de novo class II molecule expression on islet cells, and islet infiltration by T- or B-cells or macrophages was not detected. Islet capillary endothelial cells did not show signs of hypertrophy. No immunoglobulin or complement deposition within or around islets was found. These data indicate that humoral GAD autoimmunity does not necessarily associate with visible beta-cell damage.

Adenocarcinoma↗
PubMed1993

Susceptibility of human trophoblast to killing by human complement and the role of the complement regulatory proteins.

The susceptibility of trophoblast to cytolysis by human complement was investigated using cells purified to over 90% from first trimester placentae. Two assay systems were employed to measure the killing of trophoblasts, an antibody-dependent complement-mediated cytolysis and the reactive lysis. The antibody obtained from a patient with Addison's disease reacted specifically with syncytiotrophoblasts and induced a dose-dependent killing of the cells not exceeding 50% even in the presence of excess antibody and complement. The percentage of cells killed by the terminal complement complex in the reactive lysis system was somewhat higher, reaching values of 60%. Immunofluorescence analysis revealed the presence of CD46 and CD59 on all syncytiotrophoblasts, whereas CD55 was only detected on approximately 30% of the cells. Inhibition of CD46 and CD59 resulted in increased susceptibility of syncytiotrophoblasts to complement lysis. The protective function of CD55 could not be evaluated because of its reduced expression on isolated trophoblasts. These results suggest that syncytiotrophoblasts may be killed by complement and that membrane regulators to some extent protect these cells from complement damage.

Antigens, CD↗
PubMed1993

B cell activation and human immunodeficiency virus infection. V. Phenotypic and functional alterations in CD5+ and CD5- B cell subsets.

B cell dysregulation is a hallmark of human immunodeficiency virus infection. Since B lymphocytes comprise two distinct subpopulations, CD5+ and CD5- cells, we addressed their individual phenotypic and functional behavior. Seropositive patients with both limited and advanced disease progression had an increased percentage of peripheral blood CD5+ B cells, compared to seronegative controls (20.1 +/- 2.1 and 22.7 +/- 5.7, respectively, vs 17.0 +/- 3.4 in controls); however, due to the lymphopenia and reduced number of circulating B cells in infected individuals, the absolute number of CD19+CD5+ lymphocytes was actually reduced. Although HIV-specific antibodies were synthesized spontaneously in vitro only by CD5- B cells, a 10-fold lower degree of spontaneous, non-HIV-specific activation was also displayed by unstimulated CD5+ B cells. These findings indicate that B cell dysregulation during HIV infection involves both the CD5- and the CD5+ B cell compartments; moreover, in view of the putative role of CD5+ B cells in autoimmune phenomena and IL-10 production, these data reinforce the possibility that B cell dysfunction might be causally involved in AIDS pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Premature ovarian failure: autoimmunity and natural history.

OBJECTIVE: We studied the association of clinical and latent autoimmune diseases with circulating steroid-producing cells autoantibodies (SCA) in patients with premature ovarian failure (Group I). We investigated the presence of SCA in patients with organ-specific autoimmune diseases but without hypogonadism (Group II). We assessed whether SCA can be considered markers of hypergonadotrophic hypogonadism. DESIGN: In Groups I and II blood samples were taken at diagnosis. In a subset of patients with SCA without hypogonadism blood samples were taken at least yearly for 6 years for immunological and functional tests. PATIENTS: Group I included 50 females, aged 16-39 years; Group II included 3677 patients, aged 6-79 years, divided into Subgroup IIA (99 with Addison's disease alone or associated with other endocrinopathies or with hypoparathyroidism) and Subgroup IIB (3578 with insulin-dependent diabetes mellitus or thyroid autoimmune diseases). The follow-up group included nine subjects, aged 5-31 years (seven females and two males). MEASUREMENTS: SCA and other organ-specific autoantibodies were detected by standard indirect immunofluorescence using normal human tissues or passive haemagglutination tests. Gonadal functional tests included evaluation of FSH and LH levels by a RIA method; adrenocortical function included evaluation of cortisol and ACTH plasma levels by a RIA method. RESULTS: Three subgroups were identified in Group I on the basis of clinical autoimmune disease. 9/50 (18%) patients were found to have an Addison's disease (Subgroup IA) and in this subgroup SCA were present in 7/9 (78%); 10/50 (20%) had other autoimmune diseases (Subgroup IB) and SCA were found in 1/10 (10%); 31/50 (62%) did not have other clinical autoimmune diseases (Subgroup IC) and 1/31 (3%) had SCA. SCA were significantly increased in Subgroup IA vs IB (P = 0.017) and vs IC (P = 0.00002). In Group II, SCA were found in 20/3677 (0.5%); in particular, SCA were detected in 18/99 (18%) of the patients in Subgroup IIA and in 2/3578 (0.06%) of the patients in Subgroup IIB. The frequency of SCA in Subgroup IIA was found to be significantly increased with respect to that found in Subgroup IIB (P = 0.001 x 10(-5)). During follow-up, 3/7 females (42.8%) but 0/2 males developed hypergonadotrophic hypogonadism with a latency period of 10, 13 and 15 years, respectively. Three females and two males lacked clinical Addison's disease at the beginning of the study, but during follow-up 1/3 female and 2/2 males developed clinical Addison's disease with a mean latency period of 13 months. CONCLUSIONS: The results confirm the strong relationship between premature ovarian failure and other clinical autoimmune diseases, as well as the strong link existing between primary ovarian failure, Addison's disease and antibodies to steroid-producing cells. The study also suggests that in females antibodies to steroid-producing cells are serological markers of both potential hypergonadotrophic hypogonadism, and Addison's disease; however, in males these antibodies may be considered only as markers of potential Addison's disease.

Addison Disease↗
PubMed1992

Induction of autoantibodies during alpha interferon treatment in chronic hepatitis B.

Thirty-two patients with chronic hepatitis B treated with alpha interferon were tested for 12 different antibodies. Only a minority (18%) of cases developed antinuclear antibodies and none developed clinical signs of autoimmune disease. These data suggest that, at the dose regimen used, interferon therapy of chronic hepatitis B is not associated with triggering of autoimmunity.

Adult↗
PubMed1991

Expression of class I and II human leukocyte antigens by thyrocytes and lymphocytic infiltration on human thyroid tumors. An immunofluorescence study.

Surgical thyroid sections from 30 papillary carcinomas (PC), six medullary carcinomas (MC), three anaplastic carcinomas (AC), two follicular carcinomas (FC), and 16 adenomas (AD) were examined with an indirect immunofluorescence technique employing different monoclonal antibodies to evaluate the expression of human leukocyte antigen (HLA)-A, B, C (Class I) and DR, DP, DQ (Class II) by thyrocytes, together with the phenotype and distribution of inflammatory cells. Ten PC and four FC were also investigated for the presence of intercellular adhesion molecule-1 (ICAM-1). In situ deposits of immunocomplexes and circulating thyroid autoantibodies were also evaluated. An increased expression of Class I antigens was found in all PC and FC, in 33% of MC and AC, and in 31% of AD. An anomalous expression of Class II antigens was observed in 70% of PC, in 50% of FC, in 33% of AC, in 19% of AD, and in none of the MC. Expression of DP or DQ was revealed only in a portion of the DR-positive glands. A reduction of microsomal autoantigen expression was found. No ICAM-1-positive thyrocytes were detected. A moderate T-lymphocytic infiltrate was noticed only in PC, where it was correlated with DR and DP and/or DQ coexpression. B-cells and natural killer cells were virtually absent. The authors speculate that the weak Class II antigens expression, together with the partial or complete loss in microsomal autoantigen and the absence of ICAM-1 by thyrocytes, may account for the limited engagement of immunocompetent cells observed in thyroid tumors.

Adenoma↗
PubMed1991

Autoantibodies during alpha-interferon therapy for chronic hepatitis B.

The development of autoantibodies and autoimmune reactions has been reported during and after interferon (IFN) therapy. Thirteen different antibodies from the sera of 32 patients with chronic hepatitis B treated with alpha-interferon (alpha-IFN) were tested. Seventeen HBeAg-positive patients received 4.5 megaunits (MU) of recombinant IFN thrice weekly for 4 months, and 15 anti-HBe and HBV-DNA positive patients were treated with 5 MU/m2 of lymphoblastoid IFN thrice weekly for 6 months. Five patients (15%) had antinuclear antibodies (ANA) and one patient (3%) had smooth muscle antibodies before treatment. ANA appeared during IFN treatment in five (18%) of 28 previously negative patients. With discontinuation of treatment, the titer of ANA fell to undetectable levels in all patients. In contrast, none of the patients developed antibodies to endocrine organs, such as thyroid microsomal, thyroglobulin, parietal cells, pancreatic islet cell, and adrenal cortex antibodies or autoantibodies specifically associated with autoimmune liver disease such as liver kidney microsomal antibodies and antimitochondrial antibodies. There was no correlation between autoantibody positivity before therapy or autoantibody occurrence during treatment and response to IFN therapy. None of the patients developed clinical signs of autoimmune disease. These results indicate that these regimens of recombinant and lymphoblastoid IFN therapy of chronic hepatitis B are associated with a low risk of clinically significant autoimmunity.

Adult↗
PubMed1991

Islet cell surface antibodies by an ELISA method in diabetic and nondiabetic patients.

Islet cell surface antibodies (ICSA) were investigated by an ELISA method using a commercial kit in 146 subjects with and without islet cell antibodies (ICA): 28 with insulin-dependent diabetes mellitus (IDDM), 24 with noninsulin-dependent diabetes mellitus (NIDDM), 22 first-degree relatives (FDR) of IDDM patients, 31 organ-specific autoimmune patients (OSAP), 21 nonautoimmune hospitalized patients (NAP), and 20 ICA-negative normal controls. Furthermore, insulin autoantibodies (IAA) were evaluated in 87 of these subjects. ICSA were found in 11% of IDDM patients and in 14% of their FDR, in 4% of NIDDM patients, in 10% of OSAP, in 10% of NAP, and in 5% of normal controls. After absorption with rat liver powder, ICSA were detected in 7% of IDDM patients, in 5% of their FDR, in 4% of NIDDM, in 6% of OSAP, in 5% of NAP and in none of normal controls. ICSA were also detected in 4% of IAA-positive compared to 3% of IAA-negative sera. Neither correlation was found between ICSA and ICA in each group of subjects, nor between ICSA and IAA, suggesting that these autoantibodies recognize different pancreatic targets. Moreover, no significant difference was observed for ICSA prevalence in the various groups of patients studied when compared with normal controls. The prevalence of ICSA assessed by this ELISA method has been compared to that reported by other workers, who employed different techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Addison Disease↗
PubMed1991

Expression of intercellular adhesion molecule-1 (ICAM-1) on thyroid epithelial cells in Hashimoto's thyroiditis but not in Graves' disease or papillary thyroid cancer.

In order to study the possible role of antigen-independent adhesion systems in thyroid autoimmunity, we evaluated by indirect immunofluorescence the expression of lymphocyte functional antigen-1 (LFA-1) and its ligand ICAM-1 on mononuclear cell infiltrates (when present) and thyroid follicular cells of four patients with Hashimoto's thyroiditis, 30 with Graves' disease, five with papillary cancer, two with follicular adenoma, and two normal thyroid specimens. The expression of MHC class I and class II antigens was also evaluated. Most mononuclear infiltrates were LFA-1 positive, as expected. A positivity for ICAM-1 on follicular cells was observed in three out of four Hashimoto's thyroiditis specimens; such a phenomenon was totally absent in Graves' disease or any other pathological condition, or in normal tissue. MHC class II expression on thyrocytes was observed in all the patients with Hashimoto's thyroiditis, in 27 out of 30 with Graves' disease and in three out of five papillary cancer specimens.

Adult↗