| BAV subjects showed the lowest levels in MAIT and NKT cell subsets for T compartment examined (see all Figures 1(a)–1(c). Despite this, they surprisingly had mean levels of CD4+IL−17A+ cell subset, which were like those of TAV without TAA. While for the B compartment, the BAV individuals, independent to TAA disease, showed low and similar levels in the two groups (see Figures 2(a)–2(d)) in all B subsets evaluated, with the exception of the DN B cell subset. These last showed an inverse trend with more pronounced levels in BAV without TAA versus BAV individuals with TAA, but are like those in TAV without TAA (see Figure 2(e)). | (1) They would suggest that BAV individuals may have unaltered response to chronic tissue damage and, earlier than TAV individuals, that generally develop TAA disease in older ages [17].
(2) Although, they show a CD4+IL−17A+ cell subset that would seem to be not compromised, but not able probably to clonically expand, or poorly functional. Accordingly, the significantly reduced numbers of T and B lymphocyte subsets from BAV individuals would be likely similar to those observed in older people, as demonstrated in previous studies by our and other groups [33–35].
(3) The immune system in BAV cases would seem likely to appear as an “old immune system” with an altered specific clonotypic component and an increased innate/inflammatory compartment, which is consequently more easily vulnerable to internal and external stressors, frailty, disability, and disease [27–29]. In agreement with this suggestion, very marked levels of CD68+ monocyte cells have been observed by our and other groups in aorta specimens from BAV cases with TAA [3–9, 11].
(4) This might likely justify their higher incidence of chronic immune/inflammatory vascular and aortic complications, such as TAA, at younger ages than TAV subjects.
(5) A close relationship between BAV itself condition and the compromised T and B lymphocyte compartments would seem to be the cause of this altered T and B profile. Here, we hypothesize that defects in the Notch signaling pathway may be the close link between the deregulated T and B response and the BAV itself condition. |
| TAV individuals with or without TAA showed very significant levels of all T and B subsets analyzed, with a significant trend in augment in those affected by TAA (see Figures 1 and 2). The data obtained agree the results detected from our previous studies on BAV and TAA conditions. | (1) In BAV individuals, unique cellular, molecular, and genetic mechanisms are associated with TAA onset [11]. |
