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HLA Markers DQ8 and DR53 Are Associated With Lymphocytic Hypophysitis and May Aid in Differential Diagnosis
Anthony P Heaney1, Brittany Sumerel1, Raja Rajalingam1
1Departments of Medicine (A.P.H., B.S.), Neurosurgery (A.P.H., M.B., L.M.L.), and Pathology (W.H.Y.), UCLA-David Geffen School of Medicine, Los Angeles, California 90095; and Immunogenetics and Transplantation Laboratory (R.R.), Department of Surgery, University of California San Francisco, San Francisco, California 94143.
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 with melanoma who developed 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 patients with LH. The odds ratio of a patient with LH expressing the HLA-DQ8 marker is 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.
