scholarly journals Autoantibody responses in autoimmune ovarian insufficiency and in Addison's disease are IgG1 dominated and suggest a predominant, but not exclusive, Th1 type of response

2010 ◽  
Vol 163 (2) ◽  
pp. 309-317 ◽  
Author(s):  
Annalisa Brozzetti ◽  
Stefania Marzotti ◽  
Daria La Torre ◽  
Maria Luisa Bacosi ◽  
Silvia Morelli ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Side Chain ◽  
Control Group ◽  
Addison's Disease ◽  
Igg Subclass ◽  
Ovarian Insufficiency ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Autoimmune Polyendocrine Syndrome ◽  
Igg1 Isotype

ObjectiveSteroid-producing cell autoantibodies (SCAs) directed against 21-hydroxylase autoantibodies (21OHAbs), 17α-hydroxylase autoantibodies (17OHAb), and cholesterol side-chain cleavage enzyme (side-chain cleavage autoantibodies, P450sccAb) characterize autoimmune primary ovarian insufficiency (SCA-POI). The aim of the study was to analyze IgG subclass specificity of autoantibodies related to adrenal and ovarian autoimmunity.DesignWe studied 29 women with SCA-POI, 30 women with autoimmune Addison's disease (AAD) without POI, and 14 patients with autoimmune polyendocrine syndrome type 1 (APS1). 21OHAb isotypes were also analyzed in 14 subjects with preclinical AAD. Samples from 30 healthy women served as control group to determine the upper level of normality in the isotype assays.MethodsImmunoradiometric assays with IgG subclass-specific secondary antibodies.ResultsIn 21OHAb-positive sera, IgG1 isotype was detected in 90% SCA-POI and non-POI AAD sera and 67% APS1 patients. IgG1 isotype was found in 69% 17OHAb-positive SCA-POI and 100% 17OHAb-positive APS1 sera, and in 60% P450sccAb-positive SCA-POI and 80% P450sccAb-positive APS1 sera. For 21OHAb, IgG4 isotype was detected in 17% SCA-POI, 7% non-POI AAD, and 8% APS1 sera. None of the 17OHAb-positive sera was positive for IgG4. In P450sccAb-positive sera, 15% POI and 20% APS1 sera were positive for IgG4. Two 21OHAb-positive SCA-POI (7%), one 21OHAb-positive AAD (3%), three P450sccAb-positive SCA-POI (15%), and two P450sccAb-positive APS1 (20%) sera were positive for IgG4, in the absence of IgG1. All preclinical AAD sera resulted as positive for IgG1-21OHAb, but not for IgG4-21OHAb.ConclusionsThe autoantibody responses in POI and AAD are IgG1 dominated, which suggests a predominant Th1 response. Selective IgG4 isotype specificity identified a small subset of patients with Th2-oriented response.

scholarly journals Autoantibodies against recombinant human steroidogenic enzymes 21-hydroxylase, side-chain cleavage and 17alpha-hydroxylase in Addison's disease and autoimmune polyendocrine syndrome type III

2000 ◽  
pp. 187-194 ◽  
Author(s):  
R de Carmo Silva ◽  
CE Kater ◽  
SA Dib ◽  
S Laureti ◽  
F Forini ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Side Chain ◽  
Addison's Disease ◽  
Syndrome Type ◽  
Serum Samples ◽  
Side Chain Cleavage ◽  
Type Iii ◽  
Chain Cleavage ◽  
Autoimmune Polyendocrine Syndrome

OBJECTIVE: To evaluate the frequency of autoantibodies (Ab) against 21 hydroxylase (21OH), side-chain cleavage (SCC) and 17alpha-hydroxylase (17OH), in Addison's disease (AD) and autoimmune polyendocrine syndrome type III (APSIII). DESIGN AND METHODS: We used radiobinding assays and in vitro translated recombinant human (35)S-21OH, (35)S-SCC or (35)S-17OH and studied serum samples from 29 AD (18 idiopathic, 11 granulomatous) and 18 APSIII (autoimmune thyroid disease plus type 1 diabetes mellitus, without AD) patients. Results were compared with those of adrenocortical autoantibodies obtained with indirect immunofluorescence (ACA-IIF). RESULTS: ACA-IIF were detected in 15/18 (83%) idiopathic and in 1/11 (9%) granulomatous AD subjects. 21OHAb were found in 14/18 (78%) idiopathic and in the same (9%) granulomatous AD subject. A significant positive correlation was shown between ACA-IIF and 21OHAb levels (r(2)=0.56, P<0.02). The concordance rate between the two assays was 83% (24/29) in AD patients. SCCAb were found in 5/18 (28%) idiopathic (4 of whom were also positive for 21OHAb) and in the same (9%) granulomatous AD subject. 17OHAb were found in only 2/18 (11%) idiopathic and none of the granulomatous AD patients. Two APSIII patients were positive for ACA-IIF, but only one was positive for 21OHAb and SCCAb. 17OHAb were found in another two APSIII patients. CONCLUSIONS: Measurement of 21OHAb should be the first step in immune assessment of patients with AD and individuals at risk for adrenal autoimmunity, in addition to ACA-IIF. Due to their low prevalence in AD, measurement of SCCAb and 17OHAb should be indicated only for 21OHAb negative patients and/or for those with premature ovarian failure, regardless of ACA-IIF results.

P450 side-chain cleavage enzyme autoantibodies in canine Addison's disease

2013 ◽  
pp. 1-1
Author(s):  
Alisdair Boag ◽  
Kerry McLaughlin ◽  
Mike Christie ◽  
Peter Graham ◽  
Harriet Syme ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Side Chain ◽  
Addison's Disease ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

scholarly journals Autoantibodies against 21-hydroxylase and side-chain cleavage enzyme in autoimmune Addison's disease are mainly immunoglobulin G1

2004 ◽  
pp. 49-56 ◽  
Author(s):  
AS Boe ◽  
G Bredholt ◽  
PM Knappskog ◽  
TO Hjelmervik ◽  
G Mellgren ◽  
...  
Keyword(s):  
Expression System ◽  
Addison’S Disease ◽  
Side Chain ◽  
Addison's Disease ◽  
Tissue Destruction ◽  
Affinity Tag ◽  
Western Blots ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

OBJECTIVE: Immunoglobulin G (IgG) antibodies to the steroidogenic enzymes 21-hydroxylase (21OH) and side-chain cleavage enzyme (SCC) are important diagnostic markers for autoimmune Addison's disease and autoimmune polyendocrine syndromes (APS) types I and II. The characterization of autoantibody (IgG) subclasses may reveal information on how tIssue destruction takes place; therefore, IgG subtypes of anti-21OH and anti-SCC antibodies from sera of patients with Addison's disease, APS I and APS II were determined using recombinant 21OH and SCC. METHODS: SCC(51-521) and his-SCC(51-521) were expressed by pET-scc in the Escherichia coli strain BL21 Star (DE3) and inclusion bodies were purified. Full-length, human 21OH fused to an N-terminal 6x histidine affinity tag was expressed in insect cells by using the baculovirus expression system bac-to-bac. Western blots were used to investigate the IgG subtype(s) of the autoantibodies against 21OH and SCC in patients and healthy blood donors. RESULTS: All anti-SCC positive sera (n=10) contained autoantibodies of the IgG1 subclass, while four out of ten also contained IgG3. All anti-21OH positive sera (n=16) had autoantibodies exclusively against IgG1. Sera from 20 healthy subjects did not show any reactivity against 21OH or SCC. CONCLUSIONS: The finding of a predominating IgG1 response against 21OH and SCC may suggest that T helper (Th) cells of the Th1 subclass are involved in destruction of the adrenal cortex in patients with autoimmune Addison's disease.

scholarly journals II. Adrenal Cortex and Steroid 21-Hydroxylase Autoantibodies in Children with Organ-Specific Autoimmune Diseases: Markers of High Progression to Clinical Addison’s Disease

1997 ◽  
Vol 82 (3) ◽  
pp. 939-942
Author(s):  
Corrado Betterle ◽  
Marina Volpato ◽  
Bernard Rees Smith ◽  
Jadwiga Furmaniak ◽  
Shu Chen ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Adrenal Cortex ◽  
Addison’S Disease ◽  
Adrenal Function ◽  
Side Chain ◽  
Addison's Disease ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Organ Specific ◽  
Cleavage Enzyme

Abstract Adrenal cortex autoantibodies (ACA) were measured by immunofluorescence in 808 children with organ-specific autoimmune diseases without adrenal insufficiency. ACA were found in 14 children (1.7%), mostly in hypoparathyroidism (48%). Ten ACA-positive and 12 ACA-negative children were followed up for a maximum of 10 yr by evaluation of adrenocortical function (ACTH test) and autoantibody status. In all patients steroid-producing cell autoantibodies were assessed by immunofluorescence and autoantibodies to steroid 21-hydroxylase, 17α-hydroxylase, and cytochrome P450 side-chain cleavage enzyme by immunoprecipitation assay. All 10 ACA-positive patients were positive for 21-hydroxylase autoantibodies. Six were positive for steroid-producing cell autoantibodies and 5 also for autoantibodies to 17α-hydroxylase and/or P450 side-chain cleavage enzyme. Overt Addison’s disease developed in 9 (90%) ACA/21-OH-antibody-positive children after 3–121 months, and 1 remaining child had subclinical hypoadrenalism. By contrast, all ACA/21-OH antibody-negative children maintained normal adrenal function. Adrenal failure was not related to ACA titres, sex, adrenal function, type of preexisting autoimmune disorder, or human leucocyte antigens D-related status. In conclusion, in children with autoimmune endocrine diseases, ACA/21-hydroxylase autoantibodies are important predictive markers for the development of Addison’s disease.

scholarly journals Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris) Affected with Hypoadrenocorticism (Addison’s Disease)

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0143458 ◽  
Author(s):  
Alisdair M. Boag ◽  
Michael R. Christie ◽  
Kerry A. McLaughlin ◽  
Harriet M. Syme ◽  
Peter Graham ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Canis Lupus ◽  
Addison’S Disease ◽  
Side Chain ◽  
Addison's Disease ◽  
Canis Lupus Familiaris ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

scholarly journals Autoantibody Response Against NALP5/MATER in Primary Ovarian Insufficiency and in Autoimmune Addison's Disease

2015 ◽  
Vol 100 (5) ◽  
pp. 1941-1948 ◽  
Author(s):  
Annalisa Brozzetti ◽  
Mohammad Alimohammadi ◽  
Silvia Morelli ◽  
Viviana Minarelli ◽  
Åsa Hallgren ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Ovarian Insufficiency ◽  
Autoantibody Response ◽  
Autoimmune Polyendocrine Syndrome ◽  
Steroidogenic Cell ◽  
Healthy Control ◽  
Experimental Autoimmune

Abstract Context: NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (MATER) is an autoantigen in hypoparathyroidism associated with autoimmune polyendocrine syndrome type 1 (APS1) but is also expressed in the ovary. Mater is an autoantigen in experimental autoimmune oophoritis. Objectives: The objectives of the study were to determine the frequency of NALP5/MATER autoantibodies (NALP5/MATER-Ab) in women with premature ovarian insufficiency (POI) and in patients with autoimmune Addison's disease (AAD) and to evaluate whether inhibin chains are a target for autoantibodies in POI. Methods: Autoantibodies against NALP5/MATER and inhibin chains-α and -βA were determined by radiobinding assays in 172 patients with AAD without clinical signs of gonadal insufficiency, 41 women with both AAD and autoimmune POI [steroidogenic cell autoimmune POI (SCA-POI)], 119 women with idiopathic POI, 19 patients with APS1, and 211 healthy control subjects. Results: NALP5/MATER-Ab were detected in 11 of 19 (58%) sera from APS1 patients, 12 of 172 (7%) AAD sera, 5 of 41 (12%) SCA-POI sera, 0 of 119 idiopathic POI sera and 1 of 211 healthy control sera (P &lt; .001). None of 160 POI sera, including 41 sera from women with SCA-POI and 119 women with idiopathic POI, and none of 211 healthy control sera were positive for inhibin chain-α/βA autoantibodies. Conclusions: NALP5/MATER-Ab are associated with hypoparathyroidism in APS1 but are present also in patients with AAD and in women with SCA-POI without hypoparathyroidism. Inhibin chains do not appear to be likely candidate targets of autoantibodies in human POI.

scholarly journals Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison's disease

2003 ◽  
pp. 565-570 ◽  
Author(s):  
C Dal Pra ◽  
S Chen ◽  
J Furmaniak ◽  
BR Smith ◽  
B Pedini ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Premature Ovarian Failure ◽  
Addison’S Disease ◽  
Ovarian Failure ◽  
Lower Proportion ◽  
Side Chain ◽  
Addison's Disease ◽  
Steroidogenic Enzymes ◽  
Chain Cleavage ◽  
Patients At Risk

DESIGN: Adrenal cortex autoantibodies (ACA), steroid-producing cell autoantibodies (StCA) and autoantibodies (Abs) to steroidogenic enzymes in three groups of patients with premature ovarian failure (POF), 15 with autoimmune Addison's disease (AD), 26 with non-adrenal autoimmune diseases and 31 with isolated POF, have been assessed. METHODS: ACA and StCA were measured using an immunofluorescence technique. Abs to 21-hydroxylase (21-OH), to 17alpha-hydroxylase (17alpha-OH) and to cytochrome P450 side-chain cleavage (P450scc) were measured using an immunoprecipitation assay. RESULTS: Seventy-three percent of patients with POF and AD were positive for StCA, 93% for 17alpha-OH and/or P450scc Abs, 93% for ACA and 100% for 21-OH Abs. Among patients with POF and non-adrenal autoimmune diseases, 8% were positive for StCA, 12% for 17alpha-OH and/or P450scc Abs, and 8% and 12% for ACA and 21-OH Abs respectively. StCA, 17alpha-OH and/or P450scc Abs were all found in 10% of patients with isolated POF, and 13% had ACA and 21-OH Abs. All StCA-, 17alpha-OH- and/or P450scc Abs-positive patients were also positive for ACA and 21-OH Abs. Two patients with isolated POF who were ACA and 21-OH Ab positive developed AD 3 and 5 Years after the onset of POF. CONCLUSION: This study has shown that, when POF is associated with AD, StCA, 17alpha-OH and/or P450scc Abs are present in the majority of patients, while in the other two groups these Abs are detectable in a much lower proportion of patients. Measurement of ACA/21-OH Abs in some patients with POF may be important in identifying patients at risk of developing overt AD.

The mechanism of the prolonged stimulatory effect of corticotrophin on pregnenolone production by guinea-pig adrenocortical mitochondria

1986 ◽  
Vol 108 (3) ◽  
pp. 377-384 ◽  
Author(s):  
F. Lambert ◽  
J. Lammerant ◽  
J. Kolanowski
Keyword(s):  
Guinea Pigs ◽  
Mitochondrial Protein ◽  
Cholesterol Content ◽  
Treated Group ◽  
Side Chain ◽  
Control Group ◽  
Side Chain Cleavage ◽  
Protein Factor ◽  
Chain Cleavage

ABSTRACT The postulated prolonged stimulatory influence of ACTH on the adrenocortical mitochondrial synthesis of pregnenolone in response to ACTH was studied in adrenal mitochondria isolated from control guinea-pigs and from animals treated s.c. with 100 μg ACTH(1–24) twice daily on the day before the animals were killed. The animals from both groups were injected with 100 μg ACTH s.c. 30 min before killing. The mitochondrial production of pregnenolone (expressed in nmol per mg mitochondrial protein after 10-min incubation) increased from 1·52 ± 0·46 (s.e.m.) in the control group to 4·50 ± 0·59 for mitochondria from ACTH-treated animals, despite a similar free cholesterol content in the mitochondria, even when determined after a previous in-vivo treatment with aminoglutethimide to block further metabolism of cholesterol into pregnenolone. In addition, in the presence of an excess of exogenous cholesterol (100 μmol/l), the production of pregnenolone remained higher for mitochondria from ACTH-treated animals. In contrast, when the calcium concentration in the incubation medium was raised to 1 mmol/l, with subsequent enhancement in pregnenolone synthesis, the mitochondrial pregnenolone production became similar for both groups (8·28 ± 1·11 nmol in the ACTH-treated group and 9·55 ± 1·90 nmol in the control group), even in the presence of 100 μmol cholesterol/l (13·5 ±1·80 nmol in ACTH-treated animals and 14·8 ± 1·93 nmol in controls). Cycloheximide treatment administered on the day before the animals were killed was without any effect on pregnenolone production in control animals (3·51 ± 0·43 nmol before and 3·65 ± 0·63 nmol after cycloheximide treatment). In contrast, the pregnenolone production by mitochondria from ACTH-treated guinea-pigs injected with cycloheximide was reduced to a level similar to that observed in the control group (5·82± 0·23 nmol in the absence and 3·09± 0·32nmol in the presence of cycloheximide treatment). The results of the present study suggest that the prolonged stimulatory effect of ACTH on pregnenolone production involves an increase in the synthesis of a protein factor which promotes the availability of cholesterol to the side-chain cleavage system. Other mechanisms such as a stimulated synthesis of the side-chain cleavage complex itself or an increased total mitochondrial cholesterol content are not supported by our data. J. Endocr. (1986) 108, 377–384

scholarly journals Increased risk of endocrine autoimmunity in first-degree relatives of patients with autoimmune Addison’s disease

2020 ◽  
Vol 183 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Marta Fichna ◽  
Piotr P Małecki ◽  
Mirela Młodzikowska ◽  
Bolesław Gębarski ◽  
Marek Ruchała ◽  
...  
Keyword(s):  
Family Members ◽  
Addison’S Disease ◽  
Control Group ◽  
Thyroid Peroxidase ◽  
Addison's Disease ◽  
Endocrine Disorders ◽  
Endocrine Gland ◽  
First Degree Relatives ◽  
Autoimmune Polyendocrine Syndrome ◽  
Increased Risk

Objective Autoimmune conditions tend to cluster in subjects with Addison’s disease (AD) and probably also among their relatives. The aim of the study was to estimate the frequency of the endocrine gland-specific autoantibodies in first-degree relatives of patients with AD. Methods Autoantibodies were investigated in 113 family members using RIA and ELISA assays. The control group comprised 143 age-matched volunteers. Results Autoimmune diseases were diagnosed in 38.1% relatives. Hashimoto’s thyroiditis was found in 20.3%, Graves’ disease in 8.0%, vitiligo and type 1 diabetes in 3.5%, whereas AD, rheumatoid arthritis and atrophic gastritis with pernicious anaemia in 2.7% each. All studied antibodies except for islet antigen-2 (P = 0.085) were significantly more frequent in AD relatives than in controls (P < 0.05). Antibodies to 21-hydroxylase were detected in 6.2% relatives, thyroid peroxidase in 28.3%, thyroglobulin in 19.5%, glutamic acid decarboxylase in 8.0%, and zinc transporter-8 in 7.1%. Two and more autoantibodies were detected in 18.6% subjects. Significant gender difference was revealed only for aTPO, more common in female relatives (P = 0.014; OR: 3.16; 95% CI: 1.23–8.12). Circulating autoantibodies were found more frequently in the relatives of affected males (P = 0.008; OR: 3.31; 95% CI: 1.33–8.23), and in family members of patients with polyendocrine autoimmunity (P = 0.009; OR: 3.55; 95% CI: 1.31–9.57). Conclusions This study provides evidence of increased susceptibility for the endocrine autoimmunity, especially thyroid disease, in close relatives of patients with AD. Relatives of the male AD patients and of those with autoimmune polyendocrine syndrome are at particular risk and should undergo periodic screening for autoimmune endocrine disorders.

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