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.
OBJECTIVE
Steroid-producing cell autoantibodies (SCAs) directed against 21-hydroxylase autoantibodies (21OHAbs), 17alpha-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.


METHODS
We 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.


METHODS
Immunoradiometric assays with IgG subclass-specific secondary antibodies.


RESULTS
In 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.


CONCLUSIONS
The 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.
Brozzetti
Annalisa
A
Department of Internal Medicine, University of Perugia, Perugia, Italy.
Marzotti
Stefania
S
La Torre
Daria
D
Bacosi
Maria Luisa
ML
Morelli
Silvia
S
Bini
Vittorio
V
Ambrosi
Bruno
B
Giordano
Roberta
R
Perniola
Roberto
R
De Bellis
Annamaria
A
Betterle
Corrado
C
Falorni
Alberto
A
D000224:Addison Disease / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D016009:Chi-Square Distribution; D002648:Child; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000276:immunology; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D015592:Immunoradiometric Assay; D007246:Infertility / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology*; D016649:Primary Ovarian Insufficiency / Q000276:immunology*; D013255:Steroid 21-Hydroxylase / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D013255:Steroid 21-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme