Persistent systemic inflammation and atypical enterocolitis in patients with NEMO syndrome

Department of Pathology, University of California, San Francisco School of Medicine, USA
Clinical Immunology (Impact Factor: 3.67). 07/2009; 132(1):124-131. DOI: 10.1016/j.clim.2009.03.514


The NEMO syndrome is a primary immunodeficiency with immune and non-immune manifestations. The immune deficiency is heterogeneous showing defects in humoral, innate, and cell-mediated immunity. While the clinical aspects of the immunodeficiency are increasingly well understood, little is known about autoimmune manifestations in NEMO patients. We therefore sought to examine serologic markers of systemic inflammation and intestinal pathology in a kindred of patients with the NEMO syndrome. We observed persistent elevation of erythrocyte sedimentation rates in five patients, and two were symptomatic, with a chronic but atypical enterocolitis. Though pathologic lesions in these two patients were consistent with acute inflammation, sustained clinical improvement was only achieved with systemic and/or topical glucocorticoid therapy. Our data suggest that some patients with the NEMO syndrome exhibit persistent elevation of inflammatory markers similar to systemic autoimmune diseases and may subsequently develop an atypical enterocolitis.

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    • "Due to several autoinflammatory syndromes have been reported in patients with NEMO deficiency, some serological markers of systemic inflammation have been proposed to be considered within the clinical analysis of NEMO patients. For example, the persistent elevation of erythrocyte sedimentation rate (ESR) in absence of local or systemic symptoms of infection, correlate with the development of atypical enterocolitis, which improve with systemic glucocorticoid therapy [13]. Interestingly, our patient developed tissue lesions in duodenal and esophageal areas and he improved after the methylprednisolone treatment but, unfortunately , we do not have his ESR values to make such correlation. "
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    ABSTRACT: NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jun 2015 · Clinical Immunology
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    • "In addition, at least in a subgroup of patients, IBD might also be an immunodeficiency due to impaired release of pro-inflammatory cytokines by macrophages [3,4]. This hypothesis is supported by several primary immunodeficiencies that are characterized by IBD-like phenotypes such as IPEX syndrome, XIAP deficiency, and NEMO deficiency [5-7]. IL-10- and IL-10R deficiencies add to these disorders: affected patients manifest with severe early-onset enterocolitis which shows a dramatic and life-threatening progress [8-10]. "
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    Full-text · Article · Feb 2014 · BMC Immunology
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