Objective: To assess the association between serum adrenal cortex autoantibodies and histologically confirmed autoimmune lymphocytic oophoritis. Design: Controlled, prospective. Setting: Tertiary research center. Pati...Objective: To assess the association between serum adrenal cortex autoantibodies and histologically confirmed autoimmune lymphocytic oophoritis. Design: Controlled, prospective. Setting: Tertiary research center. Patient(s): Two hundred sixty-six women with 46,XX spontaneous premature ovarian failure. Intervention(s): Ovarian biopsy in 10 women. Main Outcome Measure(s): Serum adrenal cortex autoantibodies assessed by indirect immunofluorescence and autoimmune oophoritis assessed by immunohistochemical lymphocyte markers. Result(s): We obtained a histologic diagnosis of autoimmune oophoritis in four women who tested positive for adrenal cortex autoantibodies and excluded this diagnosis in ovarian biopsies from six women who tested negative for adrenal cortex autoantibodies (4/4 vs 0/6). Women with histologically confirmed autoimmune oophoritis had a greater total ovarian volume as assessed by transvaginal sonography (11.4 ±5.6 mL vs 1.5 ±0.4 mL) (mean ±SEM). They were also more likely to have subclinical adrenal insufficiency and clinical signs of androgen deficiency (3/4 vs 0/6). Overall, 10/266 women tested positive for adrenal cortex autoantibodies (3.8%, 95%confidence interval: 1.8%-6.5%). Conclusion(s): In women who present with 46,XX spontaneous premature ovarian failure as their primary concern there is a clear association between serum adrenal cortex autoantibodies and the presence of histologically confirmed autoimmune oophoritis.展开更多
Objective: To investigate mutations in the human KIT ligand gene (KITLG) gene as a mechanism of 46,XX spontaneous premature ovarian failure. The human KIT ligand gene, known also as human stem cell factor, is the liga...Objective: To investigate mutations in the human KIT ligand gene (KITLG) gene as a mechanism of 46,XX spontaneous premature ovarian failure. The human KIT ligand gene, known also as human stem cell factor, is the ligand of the c-kit transmembrane tyrosine kinase receptor (KIT). This ligand-receptor interaction is known to play important roles in mouse germ cell migration and proliferation. Design: Cross-sectional study. Setting: Clinical research center. Patient(s): Forty women with 46,XX spontaneous premature ovarian failure. Intervention(s): None. Main Outcome Measure(s): Single-stranded conformational poly-morphism analysis and DNA sequencing. Result(s): We found one nucleotide change of the KITLG coding region (811G→ T) that led to an alteration of the amino acid composition of the KITLG protein in one Caucasian patient (Asp210Tyr). However, we found the same alteration in two normal control Caucasian samples. Three nucleotide substitutions were found in the noncoding exon of KITLG (exon 10). We also identified two intronic polymorphisms. Thus, we did not identify a single significant mutation in the coding region of the KITLG gene in any of 40 patients (upper 95% confidence limit is 7.2% ). Conclusion(s): Mutations in the coding regions of the KITLG gene appear not to be a common cause of 46,XX spontaneous premature ovarian failure in North American women.展开更多
文摘Objective: To assess the association between serum adrenal cortex autoantibodies and histologically confirmed autoimmune lymphocytic oophoritis. Design: Controlled, prospective. Setting: Tertiary research center. Patient(s): Two hundred sixty-six women with 46,XX spontaneous premature ovarian failure. Intervention(s): Ovarian biopsy in 10 women. Main Outcome Measure(s): Serum adrenal cortex autoantibodies assessed by indirect immunofluorescence and autoimmune oophoritis assessed by immunohistochemical lymphocyte markers. Result(s): We obtained a histologic diagnosis of autoimmune oophoritis in four women who tested positive for adrenal cortex autoantibodies and excluded this diagnosis in ovarian biopsies from six women who tested negative for adrenal cortex autoantibodies (4/4 vs 0/6). Women with histologically confirmed autoimmune oophoritis had a greater total ovarian volume as assessed by transvaginal sonography (11.4 ±5.6 mL vs 1.5 ±0.4 mL) (mean ±SEM). They were also more likely to have subclinical adrenal insufficiency and clinical signs of androgen deficiency (3/4 vs 0/6). Overall, 10/266 women tested positive for adrenal cortex autoantibodies (3.8%, 95%confidence interval: 1.8%-6.5%). Conclusion(s): In women who present with 46,XX spontaneous premature ovarian failure as their primary concern there is a clear association between serum adrenal cortex autoantibodies and the presence of histologically confirmed autoimmune oophoritis.
文摘Objective: To investigate mutations in the human KIT ligand gene (KITLG) gene as a mechanism of 46,XX spontaneous premature ovarian failure. The human KIT ligand gene, known also as human stem cell factor, is the ligand of the c-kit transmembrane tyrosine kinase receptor (KIT). This ligand-receptor interaction is known to play important roles in mouse germ cell migration and proliferation. Design: Cross-sectional study. Setting: Clinical research center. Patient(s): Forty women with 46,XX spontaneous premature ovarian failure. Intervention(s): None. Main Outcome Measure(s): Single-stranded conformational poly-morphism analysis and DNA sequencing. Result(s): We found one nucleotide change of the KITLG coding region (811G→ T) that led to an alteration of the amino acid composition of the KITLG protein in one Caucasian patient (Asp210Tyr). However, we found the same alteration in two normal control Caucasian samples. Three nucleotide substitutions were found in the noncoding exon of KITLG (exon 10). We also identified two intronic polymorphisms. Thus, we did not identify a single significant mutation in the coding region of the KITLG gene in any of 40 patients (upper 95% confidence limit is 7.2% ). Conclusion(s): Mutations in the coding regions of the KITLG gene appear not to be a common cause of 46,XX spontaneous premature ovarian failure in North American women.
