Enteroviral Infection in a Patient with BLNK Adaptor Protein Deficiency

NaserEddin, Adeeb; Shamriz, Oded; Keller, Baerbel; Alzyoud, Raed; Unger, Susanne; Fisch, Paul; Prus, Evgenia; Berkun, Yackov; Averbuch, Diana; Shaag, Avraham; Wahadneh, Adel; Conley, Mary Ellen; Warnatz, Klaus; Elpeleg, Orly; Stepensky, Polina

doi:10.1007/s10875-015-0164-2

Cited by 19 publications

(8 citation statements)

References 19 publications

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“…His symptoms commenced at 8 months of age. Other studies that have found mutant BLNK in association with agammaglobulinemia can be found here [87][88][89]. They confirm recurrent otitis and sinopulmonary infections as the most common initial presentation of BLNK deficiency [88,89].…”

Section: Blnk Deficiencysupporting

confidence: 77%

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Pulmonary Manifestations of Predominantly Antibody Deficiencies

Saghazadeh

Rezaei

2019

Pulmonary Manifestations of Primary Immunodeficiency Diseases

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Section: Blnk Deficiencysupporting

confidence: 77%

“…They confirm recurrent otitis and sinopulmonary infections as the most common initial presentation of BLNK deficiency [88,89]. However, other clinical manifestations included diarrhea, enteroviral infection, arthritis, dermatitis, and bronchiectasis [89].…”

Section: Blnk Deficiencymentioning

confidence: 64%

Pulmonary Manifestations of Predominantly Antibody Deficiencies

Saghazadeh

Rezaei

2019

Pulmonary Manifestations of Primary Immunodeficiency Diseases

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“…On the other hand, macrophage migration inhibitory factor (MIF) which is important for the acute immune response [35] was significantly downregulated as well as chemokine C-C motif receptor 1 (CCR1) playing a role in recruitment of leukocytes to the effector site [36] (fold change = 0.45 and 0.36, respectively). Furthermore, sialic acid binding Ig-like lectin 10 (SIGLEC10) which is a negative regulator of immune signaling by functioning as an inhibitory receptor [37] and B cell linker (BLNK) , an adaptor molecule linked to the pathway activated by B-cell antigen receptor signals [38], were significantly downregulated, with fold changes of 0.01 and 0.26, respectively.…”

Section: Resultsmentioning

confidence: 99%

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

Kieckens

Rybarczyk

Li³

et al. 2016

BMC Genomics

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Background: Enterohaemorrhagic Escherichia coli (EHEC), like E. coli O157:H7 are frequently detected in bovine faecal samples at slaughter. Cattle do not show clinical symptoms upon infection, but for humans the consequences after consuming contaminated beef can be severe. The immune response against EHEC in cattle cannot always clear the infection as persistent colonization and shedding in infected animals over a period of months often occurs. In previous infection trials, we observed a primary immune response after infection which was unable to protect cattle from reinfection. These results may reflect a suppression of certain immune pathways, making cattle more prone to persistent colonization after re-infection. To test this, RNA-Seq was used for transcriptome analysis of recto-anal junction tissue and ileal Peyer's patches in nine Holstein-Friesian calves in response to a primary and secondary Escherichia coli O157: H7 infection with the Shiga toxin (Stx) negative NCTC12900 strain. Non-infected calves served as controls. Results: In tissue of the recto-anal junction, only 15 genes were found to be significantly affected by a first infection compared to 1159 genes in the ileal Peyer's patches. Whereas, re-infection significantly changed the expression of 10 and 17 genes in the recto-anal junction tissue and the Peyer's patches, respectively. A significant downregulation of 69 immunostimulatory genes and a significant upregulation of seven immune suppressing genes was observed.

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“…To date, 6 patients with mutations in the scaffold protein BLNK have been described (52–55). These patients lack expression of BLNK as they harbor either nonsense or frameshift mutations, generally having clinical findings that are comparable to those seen in patients with mutations in BTK.…”

Section: Discussionmentioning

confidence: 99%

Hypomorphic Mutations in the BCR Signalosome Lead to Selective Immunoglobulin M Deficiency and Impaired B-cell Homeostasis

Geier¹,

Sauerwein²,

Leiss-Piller³

et al. 2018

Front. Immunol.

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B cell activation via the B cell receptor (BCR) signalosome involves participation of signaling molecules such as BTK and BLNK. Genetic defects in these molecules are known to impair B cell differentiation and subsequently lead to agammaglobulinemia. Here we identified novel mutations in BTK and BLNK in two unrelated patients that perturb the intrinsic B-cell receptor signaling pathway and lead to selective IgM deficiency, whereas production of other immunoglobulin isotypes and IgG antibody response remain intact. Currently it is unknown how BCR signaling strength affects mature B cell development in humans. Both patients show reduced levels of BCR signalosome phosphorylation as well as impaired BCR-dependent Ca2+ influx, which was accompanied by a marked decrease in IgD+IgM+CD27+ MZ-like B-cells. We further describe reduced expression of essential B cell differentiation factors such as BAFF-R and T-Bet in the patients' B-cells, which might contribute to the observed deficiency of MZ-like B cells. MZ-like B cells are known to produce natural IgM antibodies that play an essential role in immune homeostasis. By using surface plasmon resonance (SPR) technology and a synthetic blood group A trisaccharide as antigen we were able to show that both patients lack the presence of anti-blood group A IgM considered to be prototypical natural antibodies whereas IgG levels were normal. Antibody binding dynamics and binding affinity of anti-blood group A IgG were comparable between patients and healthy controls. These results indicate that human IgM deficiency can be associated with signaling defects in the BCR signalosome, defective production of natural IgM antibodies in the blood group A/B/0 system and abnormalities in B cell development.

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Enteroviral Infection in a Patient with BLNK Adaptor Protein Deficiency

Cited by 19 publications

References 19 publications

Pulmonary Manifestations of Predominantly Antibody Deficiencies

Pulmonary Manifestations of Predominantly Antibody Deficiencies

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

Hypomorphic Mutations in the BCR Signalosome Lead to Selective Immunoglobulin M Deficiency and Impaired B-cell Homeostasis

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