Status Reports of Research Work Funded by Previous Fundraisers

          These are the latest updates (September 2009) from the researchers that were awarded the monies from the restricted grant held by NORD.

          Daniela Cihakova, MD, PhD (Johns Hopkins)

          Chronic Candida albicans infection is one of the most prevalent symptoms of APECED found in virtually all patients. It often appears in early childhood and is very resistant to treatment. It can substantially impact a patient's quality of life, causing not only chronic pain and cosmetic problems, but also an increased risk of developing cancer. Understanding the immunological defect that makes APECED patients so prone to this particular infection is essential for developing better treatment strategies. With a support from NORD we are studying the mechanism of chronic Candida infection in Aire KO mice, which may guide pathomechanistic studies, as well as novel treatment strategies in human APECED patients.

          Matthias Wabl, PhD, (UC, San Francisco)

          A deficiency in the autoimmune regulator (AIRE)—a protein needed to help our immune system distinguish ourselves from invading microbes—leads to a large variety of clinical outcomes in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). But the AIRE deficiency by itself does not explain the failure of patients to fight off fungal infections (with the help of so-called antibodies). Our immune system stands ready to meet all kinds of different microbial threats, but it needs to get into focus for a particular pathogen. It does so by expanding the appropriate white blood cells specific to that pathogen and by sharpening their discrimination power. Our work explains the failure to mount good immune responses in APECED patients by suggesting that more antibody-producing white blood cells with irrelevant reactivity are expanded than in healthy persons, which, in turn, leads to an unfocused response.