Springer Science and Business Media LLC

X-linked agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in X-linked agammaglobulinemia (XLA), the spectrum of gastrointestinal manifestations has not previously been fully explored. We present a case report of a family with two affected patients with XLA. Given the gastrointestinal involvement of the grandfather in this family, we performed a retrospective descriptive analysis of XLA patients with reported diagnoses of GI manifestations and inflammatory bowel disease (IBD) or enteritis registered at the United States Immunodeficiency Network, a national registry of primary immunodeficiencies. In this cohort of patients with XLA, we found that up to 35% had concurrent gastrointestinal manifestations, and 10% had reported diagnoses of IBD or enteritis. The most commonly reported mutations were missense, which have been associated with a less severe XLA phenotype in the literature. The severity of symptoms were wide ranging, and management strategies were diverse and mainly experimental. Patients with XLA may require close monitoring with particular attention for GI manifestations including IBD and infectious enteritis. Further studies are needed to improve diagnosis and management of GI conditions in XLA patients.

Four in five children with inborn errors of immunity globally remain undiagnosed. These figures are disproportionally high in low-income countries like Ethiopia. Apart from the inclusion of basic overviews of these disorders in to postgraduate pediatric curricula, little effort has been placed in to establishing clinical immunology training programs. This report summarizes the existing epidemiology of inborn errors of immunity in Ethiopia, unique presentations in Ethiopian children, challenges faced in diagnosing them, and efforts to improve their management.

Cytokine production by innate immune cells is initiated by signaling downstream of pattern recognition receptors, including Toll-like receptors. A subset of cytokines, including IL-1β and IL-18, require post-translational proteolysis before secretion, which provides a second mechanism of regulation. This proteolysis is dependent upon caspase 1, which is activated by Nod-like receptor (NLR) signaling. NLRC4 (previously named Ipaf) activates caspase 1 in response to bacterial virulence factors including type III and IV secretion systems (T3SS and T4SS). NLRC4 recognizes T3SS/T4SS in two ways: indirectly by detecting flagellin, and directly by detecting the T3SS rod protein. Both flagellin and rod protein are unintentionally delivered to the mammalian cytosol by the bacterium through the T3SS.

Chemokines are low molecular weight chemotactic peptides that bind seven transmembrane-spanning, G protein-coupled receptors and deliver signals leading to T cell costimulation, hematopoeisis, cytokine expression, T cell differentiation, and integrin activation. Experimental autoimmune encephalomyelitis (EAE) is a CD4+ Th1-mediated demyelinating disease of the central nervous system (CNS) that serves as a model for multiple sclerosis (MS). A hallmark in the pathogenesis of this CNS demyelinating disease is the emigration of T cells and monocytes from the blood to the CNS. There are several considerations that suggest a role for chemokines in the influx of inflammatory cells and the resulting disease process including a tight temporal expression pattern with relationship to disease activity and prevention of disease development by in vivo neutralization. We review the evidence that temporal and spatial expressions of chemokines are crucial factors, complementing adhesion molecule upregulation, that regulate EAE and potentially MS disease activity as well as the functions of chemokines in Th1 and Th2 biology.

Several immunoglobulin (IG) preparations have been approved for the immunomodulatory treatment of the neurological autoimmune diseases (AID) Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). Although efficacy has been proven in randomised clinical trials, long-term outcome data on drug utilization, effectiveness, tolerability, health related quality of life, and economic variables are lacking. In the prospective, observational internet-based SIGNS registry, patients of all age groups are eligible if they have received or are scheduled for IG therapy for neurological AID or primary or severe secondary immunodeficiency. Of the 306 patients currently included in the database (1 November 2011), 51 have neurological AID (27 males; mean age 56 ± 15 years): 21 CIDP, 7 MMN, 11 multiple sclerosis (MS), 6 myasthenia gravis, 2 myositis, 4 others (no cases of GBS). Mean duration of disease since first symptoms was 7.8 years, and disease duration since diagnosis was 5.9 years. Eight different IG preparations have been reported as current therapy. According to SF-36, patients’ quality of life is substantially impaired. Present data indicate some off-label use of IG (e.g. in MS) in patients with neurological AID. Quality of life in these patients is substantially compromised. Increasing patient numbers and extended follow-up periods will provide data on treatment concepts and disease development in AID patients.