Markers of humoral and cell-mediated immune response in primary autoimmune hypophysitis: a pilot study

Abstract

Introduction Primary autoimmune hypophysitis (PAHs) is a rare inflammatory disease of the pituitary gland. Although largely investigated, the pathogenesis of PAH is not completely clarified. We aimed to investigate the immune response in PAHs. Material and methods Serum anti-pituitary and anti-hypothalamus antibodies (respectively APAs and AHAs) were investigated though an indirect immunofluorescence on monkey hypophysis and hypothalamus slides, serum cytokines though an array membrane and cell-mediated immunity though the white blood cells count. Results Nineteen PAH cases entered the study. APA or AHA were identified in all cases. APA were detected in 13 patients (68.4%) and AHA in 13 patients (68.4%). Ten patients (52.6%) were simultaneously positive for both APA and AHA. The prevalence of APAs and AHAs was higher as compared to those observed in 50 health controls (respectively 14% p < 0.001 and 24% p = 0.004) and in 100 not-secreting pituitary adenoma (NFPAs) (respectively 22% p = 0.002 and 8% p < 0.001). Similarly, the prevalence of simultaneous positivity for APA and AHA (52.9%) was higher as compared to the those detected in patients affected by NFPAs (0%; p < 0.001) and in health controls (16% p = 0.002). No differences were identified between PAHs and controls at qualitative and quantitative analysis of serum cytokines and white blood cells count. Conclusions This study suggest that APA and AHA may be detected in an high percentage of PAH cases and that their simultaneous identification may be useful for the differential diagnosis between PAH and NFPAs, in an appropriate clinical context.

Pituitary Enlargement and Hypopituitarism in Patients Treated with Immune Checkpoint Inhibitors: Two Sides of the Same Coin?

“…These findings may explain the different behaviors of central hypoadrenalism in patients treated with ipilimumab and nivolumab. In our study, anti-pituitary or anti-hypothalamus antibodies were present in both types of IIHs, which aligns with our previous study on primary autoimmune hypophysitis, where the prevalence of both APA and AHA was 68.4% [ 22 ]. A recent study of 62 cancer patients treated with ICIs showed that APA positivity was similar among the five patients who developed IIHs (80%) compared to those with an ACTH deficit (88.2%) [ 39 ].…”

“…Anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) were measured as previously described [ 21 ] using an indirect immunofluorescence method on monkey hypophysis slides (MHY) and monkey hypothalamus slides (MTH) provided by Biosystem S.A. [ 22 ]. The serum samples were tested for the presence of APA and/or AHA by their binding to the corresponding antigens on the monkey sections.…”

Is There A Connection Between Primary Hypophysitis and Celiac Disease?

“…Nineteen patients with PH had higher APA and AAVP values than nonfunctioning pituitary adenomas and healthy controls. Based on this result, they emphasized that these two antibodies can be used in the differential diagnosis of nonfunctioning pituitary adenomas and PH [24]. Another study examined APA in patients receiving immune checkpoint inhibitors; antibodies that were negative at baseline were positive in 80 % of patients a few weeks after treatment [25].…”

Molecular and Genetic Immune Biomarkers of Primary and Immune-Therapy Induced Hypophysitis: From Laboratories to the Clinical Practice

“…The clinical relevance of APAs has been keenly discussed in previous research and APAs were widely considered a pathogenic marker of hypophysitis rather than a diagnostic tool. In fact, APAs were reported in other autoimmune disorders of the pituitary gland or in autoimmune systemic diseases, such as Sheehan’s syndrome, idiopathic growth hormone (GH) deficiency, idiopathic hyperprolactinemia, idiopathic hypopituitarism, brain traumatic injury, autoimmune polyendocrine syndromes and empty sella syndrome, but also in patients with pituitary adenomas or in healthy individuals [ 14 , 16 , 17 ]. The experimental hypophysitis of SJL/J models showed that APAs may be detected with a higher concentration in the initial days after mouse immunization and gradually reduce thereafter [ 11 ].…”