Evidence for a Role of TGF-β-Activated Kinase 1 and MAP3K7 Binding Protein 3 in Peanut-Specific T-Cell Responses

Abstract

Peanut allergy is considered to be the most common cause for food-induced anaphylaxis. Currently, no approved treatment is available. Avoidance is the only measure to prevent anaphylactic reactions to peanuts. T-helper cells are of special importance for the sensitization process and the maintenance of allergic inflammation. Identifying markers of allergen-specific T-cell responses may help to develop novel treatment approaches. Therefore, we aimed to define new T-cell target genes in Ara h 2-specific T cells and to investigate the possibility of using them as biomarkers of peanut allergy in peripheral blood mononuclear cells (PBMCs). We performed whole mRNA array analysis (whole human genome oligo microarray) of in vitro expanded Ara h 2-specific T cells (CFSE^lowCD3⁺CD4⁺) from 5 peanut-allergic (PA) and 5 non-peanut-sensitized individuals. Expression of selected genes as a result of a two-step bioinformatic approach was confirmed in a second cohort by quantitative PCR. TGF-β- activated kinase 1 and MAP3K7 binding protein 3 (TAB3), calcium/calmodulin-dependent protein kinase type IV (CAMK4) and HemK methyltransferase family member 1 (HEMK1) were significantly upregulated in Ara h 2-specific T cells of PA patients. In addition, the expression of these genes was also assessed in unstimulated PBMCs from a cohort (n = 43) of PA, atopic non-PA, and nonatopic controls. Interestingly, in unstimulated PBMCs, TAB3 expression was significantly downregulated in PA patients compared to atopic non-PA individuals. Thus, TAB3 may play a significant role at the level of T-cell activation and may also be a candidate biomarker for PA.

Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24+CD38hi B Cells

“…As CD24 + CD38 hi B cells increased dramatically during Peg-IFNα-2b therapy, we further investigated whether these CD24 + CD38 hi B cells are relevant for clinical outcomes. CD24 + CD38 hi B cells are found at low frequencies (<5% of B cells) in normal healthy human controls ( 34 ). Depending on whether the percentage of CD24 + CD38 hi B cells in HBV patients at 72 weeks after the start of PEG-IFNα-2b therapy are higher than that in the normal healthy controls or not, patients were classified into the more CD24 + CD38 hi B cell group (CD24 + CD38 hi B cells ≥ 5% of B cells) or the fewer CD24 + CD38 hi B cell group (CD24 + CD38 hi B cell <5% of B cells).…”

Recent developments and highlights in food allergy

“…54 Another study reported that TGFbeta-activated kinase 1 and MAP3K7 binding protein 3 (TAB3) has been linked to T cells in peanut allergy. 55 Moreover, the Barwon Infant Study (BIS) showed that the proportion of naïve regulatory T cells at birth could be used as a marker of food allergy development in infancy. 56 This adds to the established role of regulatory cell subsets early in life.…”

“…In a different approach, the inhibitory transmembrane protein, which is part of the immunoglobulin superfamily CD200R, has been identified as a highly upregulated marker on peanut‐specific T cells, Th2, Tc2, ILC2, and basophils . Another study reported that TGF‐beta–activated kinase 1 and MAP3K7 binding protein 3 (TAB3) has been linked to T cells in peanut allergy . Moreover, the Barwon Infant Study (BIS) showed that the proportion of naïve regulatory T cells at birth could be used as a marker of food allergy development in infancy .…”