SummaryOlder people suffer from a decline in immune system, which affects their ability to respond to infections and to raise efficient responses to vaccines. Effective and specific antibodies in responses from older individuals are decreased in favour of non-specific antibody production. We investigated the B-cell repertoire in DNA samples from peripheral blood of individuals aged 86-94 years, and a control group aged 19 -54 years, using spectratype analysis of the IGHV complementarity determining region (CDR)3. We found that a proportion of older individuals had a dramatic collapse in their B-cell repertoire diversity.
Sequencing of polymerase chain reaction products from a selection of samples indicated that this loss of diversity was characterized by clonal expansions of B cells in vivo.Statistical analysis of the spectratypes enabled objective comparisons and showed that loss of diversity correlated very strongly with the general health status of the individuals; a distorted spectratype can be used to predict frailty. Correlations with survival and vitamin B12 status were also seen. We conclude that B-cell diversity can decrease dramatically with age and may have important implications for the immune health of older people. B-cell immune frailty is also a marker of general frailty.
Expression of C3 alleles by donor renal cells appears to have a differential effect on late graft outcome. Among white C3S/S recipients, receipt of a C3F/F or C3F/S donor kidney, rather than a C3S/S donor kidney, is associated with a significantly better long-term outcome. These findings suggest that the two alleles have functional differences.
Actinic prurigo (AP) and polymorphic light eruption (PLE) both belong to the group of idiopathic photodermatoses, but it remains controversial whether AP is a distinct photodermatosis or a variant of PLE. The aim of this study, by collecting data from 119 patients with features of these disorders, was to establish whether specific criteria could be used to distinguish AP from PLE prospectively. We found that presence of the eruption on both exposed and covered sites, its occurrence in winter, persistence of lesions beyond 4 weeks, mucosal and conjunctival involvement, excoriation and scarring of the skin were important features of AP which were not typical of PLE. On this basis, confident clinical diagnoses could be reached in 103 of 119 patients (87%), 57 with AP and 46 with PLE, supported by phototesting and negative lupus serology. HLA typing subsequently confirmed the strong association (90%) between AP and the DR4 allele, in particular with the rare subtype DRB1*0407 which was present in 60% of these patients. No HLA association was found in PLE. In the 16 remaining cases, however, clinical overlap meant that no definite diagnosis could be made; these patients were notionally described as having persistent PLE (PPLE). Demographic and HLA data in this group suggested that PPLE was perhaps most appropriately grouped with PLE. In addition to those patients who were difficult to classify, 35% of our typical AP patients also described clinical progression from PLE to AP, AP to PLE or coexistence of both AP and PLE. In conclusion, our study suggests that while AP and PLE are clinically distinct conditions in most cases, they may perhaps share a common pathophysiological basis. The AP phenotype may be determined by HLA and perhaps other factors in patients otherwise predisposed to PLE.
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