Franca, Tabata T.
Barreiros, Lucila A.
al-Ramadi, Basel K.
Ochs, Hans D.
Total Authors: 6
 Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, 1730 Lineu Prestes Ave, BR-05508000 Sao Paulo, SP - Brazil
 UAE Univ, Coll Med & Hlth Sci, Dept Med Microbiol & Immunol, Al Ain - U Arab Emirates
 Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 - USA
 Seattle Childrens Res Inst, Seattle, WA - USA
 Univ Freiburg, Fac Med, Med Ctr, Dept Rheumatol & Clin Immunol, CCI, Freiburg - Germany
Total Affiliations: 5
EXPERT REVIEW OF CLINICAL IMMUNOLOGY;
MAY 4 2019.
Web of Science Citations:
Introduction: CD40 ligand (CD40L) deficiency or X-linked Hyper-IgM syndrome is a severe primary immunodeficiency caused by mutations in the CD40L gene. Despite currently available treatments, CD40L-deficient patients remain susceptible to life-threatening infections and have poor long term survival. Areas covered: Here, we discuss clinical and immunological characteristics of CD40L deficiency as well as current therapeutic strategies used for patient management. This review highlights that beyond B cell defects, patients' susceptibility to opportunistic pathogens might be due to impaired T cell and innate immune responses. In this context, we discuss how better knowledge of CD40L function and regulation may result in the development of new treatments. Expert opinion: Despite the introduction of hematopoietic stem-cell transplantation, immunoglobulin replacement, granulocyte colony-stimulating factor (G-CSF) administration, and prophylactic antibiotic therapies, life-threatening infections still cause high morbidity and mortality among CD40L-deficient patients. The reasons for this inadequate response to current therapies remains poorly understood, but recent reports suggest the involvement of CD40L-CD40 interaction in early stages of the innate immune system ontogeny. The development of novel gene therapeutic approaches and the use of redirected immunotherapies represent alternative treatment methods that could offer reduced morbidity and mortality rates for patients with CD40L deficiency. (AU)