Publications by authors named "D A Fulcher"
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them, SH2B3-a negative regulator of cytokine and growth factor receptor signaling-harbors rare coding variants in over 5% of SLE patients.
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- Autosomal dominant loss-of-function variants in CTLA-4 cause immune system issues like autoimmunity and immunodeficiency, known as IDAIL, which show variability in symptoms due to genetic modifiers.* -
- The study identifies a patient with a pathogenic CTLA-4 variant and a rare DECTIN-1 variant that affects DECTIN-1's function, leading to reduced immune regulation.* -
- DECTIN-1 is shown to enhance the differentiation of regulatory T cells and plays a critical role as a modifier that influences the severity of immune defects caused by CTLA-4 haploinsufficiency.*
As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency (PAD), analysis of affected patients could yield insights into T-cell differentiation and explain how environmental exposures modify clinical phenotypes conferred by single-gene defects. CD57 marks dysfunctional T cells that have differentiated after antigenic stimulation. Indeed, while circulating CD57 CD4 T cells are normally rare, we found that they are increased in patients with PAD and markedly increased with CTLA4 haploinsufficiency or blockade.
View Article and Find Full Text PDFBackground: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.
Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.
Methods: We identified 191 patients from 33 countries with 72 unique mutations.
Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand.
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