I. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison's disease.
Adrenal cortex antibodies (ACA) were measured by immunofluorescence in 8840 adult patients with organ-specific autoimmune diseases without overt hypoadrenalism. Sixty-seven (0.8%) patients were ACA-positive, with the highest prevalence in those with premature ovarian failure (8.9%). Forty-eight ACA-positive and 20 ACA-negative individuals were enrolled into a prospective study. Antibodies to steroid 21-hydroxylases (21-OH), steroid 17 alpha-hydroxylase (17 alpha-OH) and cytochrome P450 side chain cleavage enzyme (P450scc) were measured by immunoprecipitation assay. Human leucocyte antigens D-related (HLA-DR) genotyping was also carried out and adrenal function assessed by ACTH test. On enrollment, 75% of ACA-positive patients had a normal adrenal function, while 25% revealed a subclinical hypoadrenalism. 21-OH antibodies were positive in 91% of ACA-positive sera. Eleven patients were positive for steroid-cell antibodies by immunofluorescence, and 9 revealed a positivity for antibodies to 17 alpha-OH and/or P450scc. During the prospective study, overt Addison's disease developed in 21% and subclinical hypoadrenalism in 29% of ACA-positive patients, while 50% maintained normal adrenal function. Progression to Addison's disease was more frequent in patients with subclinical hypoadrenalism, high titers of ACA and higher levels of 21-OH antibodies, complement-fixing ACA and HLA-DR3 status. All 20 persistently ACA-negative patients were also negative for antibodies to 21-OH, 17 alpha-OH, and P450scc, and all maintained normal adrenal function during follow-up. In conclusion, the detection of ACA/21-OH antibodies in adults is a marker of low progression toward clinical Addison's disease.
Betterle
C
C
Chair of Clinical Immunology and Allergy, University of Padova, Italy.
Volpato
M
M
Rees Smith
B
B
Furmaniak
J
J
Chen
S
S
Greggio
N A
NA
Sanzari
M
M
Tedesco
F
F
Pedini
B
B
Boscaro
M
M
Presotto
F
F
D000224:Addison Disease / Q000209:etiology*; D000302:Adrenal Cortex / Q000276:immunology*; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D001327:Autoimmune Diseases / Q000150:complications* / Q000276:immunology*; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D011446:Prospective Studies; D013255:Steroid 21-Hydroxylase / Q000276:immunology*
D001323:Autoantibodies; D015415:Biomarkers; D013255:Steroid 21-Hydroxylase