HLA markers DQ8 and DR53 are associated with lymphocytic hypophysitis and may aid in differential diagnosis

Abstract

Importance: Lymphocytic hypophysitis (LH) is a poorly understood autoimmune disorder of the pituitary gland. Symptoms include headache, pituitary dysfunction, visual disturbances, and neurological deficits. The diagnosis can be made based on clinical and biochemical findings, but for atypical presentations, no circulatory diagnostic biomarkers exist, and a pituitary biopsy is necessary for diagnosis. Objectives: We used high-resolution human leukocyte antigen (HLA) screening assays to investigate a relationship between specific HLA markers and LH. Design: This was a retrospective analysis. Setting: The study was conducted at a tertiary referral center. Subjects: Fifteen patients with sporadic LH, 4 patients withmelanomawhodeveloped hypophysitis after administration of cytotoxic T lymphocyte antigen 4 (CTLA4) antibodies, and 1 patient with sarcoid-associated hypophysitis were evaluated. Intervention: Clinical data, including endocrine function, were assessed, and HLA typing was performed in all 20 patients with hypophysitis, 50 control patients with other sellar abnormalities, and 4 CTLA4 antibody-treated patients without hypophysitis. Results: Two major histocompatibility class II HLA markers, DQ8 and DR53, were found in 13 of 15 (87%) and 12 of 15 (80.0%) patients with sporadic LH, respectively. In contrast, none of the 4 patients who developed hypophysitis after administration of the CTLA4 antibodies exhibited the HLA-DQ8 marker and only 1 of 4 (25%) exhibited the HLA-DR53 marker. In a parallel group of 50 control subjects with sellar masses and 4 CTLA4 antibody-treated patients who did not develop evidence of pituitary failure, the candidate HLA subtypes were found in-20% for DQ8 and-48% for DR53, respectively. Conclusion and Relevance: The HLA markers, DQ8 and DR53, were found to be commonly present in patientswithLH.Theoddsratio ofapatientwithLHexpressing theHLA-DQ8markeris 23.1-fold higher than that of a patient with another sellar mass. HLA-DQ8 testing may assist in diagnosis and avoid unnecessary biopsies in patients with atypical LH.