Three Cases of Alemtuzumab Associated Graves Disease Following Immunosuppression Withdrawal After Clinical Islet Transplantation

Student Researcher:
Alanna Dunn

Supervisor / Principle Investigator:
Dr. Peter Senior

MD Class of 2020


Background: Alemtuzumab (an anti-CD52 monoclonal antibody) is used for induction prior to clinical islet transplantation (CIT) followed by tacrolimus and mycophenolate for maintenance immunosuppression.. In multiple sclerosis (MS), alemtuzumab has been linked to a high incidence of autoimmune thyroid disease (AITD) in 30-40% of subjects; however, this has not been observed after CIT.

Case Series: Three female subjects (age 27, 48, 50) with type 1 diabetes (T1DM) who received CIT are presented. Each received a dose of alemtuzumab (20-30mg) prior to each of 2 islet infusions which were separated by 2-16 months. One subject had pre-existing Addison’s, and one had pre-existing rheumatoid arthritis and systemic lupus erythematosus (SLE), but none had thyroid disease. All 3 cases subsequently presented with symptoms of hyperthyroidism, elevated thyroid hormone, suppressed thyroid stimulating hormone (TSH), positive TSH receptor antibodies (TRAb), and were diagnosed with Graves disease. The interval between last dose of alemtuzumab and appearance of Graves was 12-68 months. All have been successfully treated with methimazole. The only thyroid associated complication was one case of thyroid eye disease.

Discussion: Despite high rates of AITD after alemtuzumab in MS, these are the first reports of alemtuzumab associated Graves disease after CIT. In CIT, withdrawal of maintenance IS may be associated with risk of alemtuzumab associated AITD. Further studies will systematically examine the incidence of AITD in CIT cohorts.