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

Sabrina Chiloiro,Egidio Stigliano,Pier Paolo Mattogno,Quintino Giorgio D’Alessandris,Flavia Angelini,Antonella Giampietro,Alfredo Pontecorvi,Liverana Lauretti,Vincenzo Arena,Tommaso Tartaglione,Antonio Bianchi,Laura De Marinis

doi:10.1007/s12020-021-02612-5

Abstract

IntroductionPrimary 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 methodsSerum 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.ResultsNineteen 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.ConclusionsThis 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.

Highlights

Primary autoimmune hypophysitis (PAHs) is a rare inflammatory disease of the pituitary gland
APA or AHA were identified in all cases: APA were detected in 13 patients (68.4% of cases) and AHA in 13 patients (68.4% of cases)
The prevalence of coexisting 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 (8 of 50 cases: 16% p = 0.002)

Summary

Introduction

Primary autoimmune hypophysitis (PAHs) is a rare inflammatory disease of the pituitary gland and represents an emerging problem, as in recent years, an increased number of cases has been described [1]. Cerebrospinal fluid enters the brain via peri-arterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4 and drives the perivenous drainage of the interstitial fluids and its solute [2]. This recently discovered glymphatic system represents a novel pathway for the drainage of the cerebrospinal fluid and a more conventional path for the immune cells to egress the central nervous system [3, 4]. The dysfunction of the glymphatic system was described in neurological diseases, associated with protein accumulation within the central nervous system and immune disorders, as the multiple sclerosis and the Alzheimer’s disease

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