CD40 ligand deficiency: treatment strategies and novel therapeutic perspectives

Autor(es)

Franca, Tabata T. ^[1] ; Barreiros, Lucila A. ^[1] ; al-Ramadi, Basel K. ^[2] ; Ochs, Hans D. ^{[3, 4]} ; Cabral-Marques, Otavio ^[5] ; Condino-Neto, Antonio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, 1730 Lineu Prestes Ave, BR-05508000 Sao Paulo, SP - Brazil

^[2] UAE Univ, Coll Med & Hlth Sci, Dept Med Microbiol & Immunol, Al Ain - U Arab Emirates

^[3] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 - USA

^[4] Seattle Childrens Res Inst, Seattle, WA - USA

^[5] Univ Freiburg, Fac Med, Med Ctr, Dept Rheumatol & Clin Immunol, CCI, Freiburg - Germany

• Tipo de documento: Artigo de Revisão
• Fonte: EXPERT REVIEW OF CLINICAL IMMUNOLOGY; v. 15, n. 5, p. 529-540, MAY 4 2019.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 16/22158-3 - Mecanismos genético-moleculares nas imunodeficiências primárias
• Beneficiário: Antonio Condino Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/04187-9 - Avaliação funcional de neutrófilos em pacientes com deficiência de cd40l
• Beneficiário: Tábata Takahashi França
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/09407-0 - Bases genéticas imunológicas da susceptibilidade à infecção pelo Zika Virus em humanos
• Beneficiário: Lucila Akune Barreiros
• Modalidade de apoio: Bolsas no Brasil - Doutorado