ABSTRACT
Purpose: We investigated the association between self-rated health (SRH) and cancer incidence and SRH and all-cause mortality among Norwegian women. Population and Methods: We used data from 110,104 women in the Norwegian Women and Cancer (NOWAC) cohort aged 41-70 years at baseline. We used flexible parametric survival analysis with restricted cubic splines to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SRH and mortality in the entire cohort. We employed the same method in a multistate design to assess associations between baseline SRH and 1) cancer incidence, and 2) all-cause mortality in subgroups of women who did and did not receive a cancer diagnosis during follow-up. Results: With very good SRH as reference category for all associations and median age at end of follow-up, lower SRH was associated with increased mortality (HRgood SRH 1.19, 95% CI 1.12-1.26) and HRpoor SRH 1.81, 95% CI 1.66-1.97). Lower SRH at baseline was associated with cancer incidence (HRgood SRH 1.14, 95% CI 1.08-1.20 and HRpoor SRH 1.44, 95% CI: 1.32-1.58). Poor baseline SRH was associated with increased mortality for women who received a cancer diagnosis (HRpoor SRH 1.20, 95% CI 1.04-1.39), and SRH showed a strong association with increased mortality for women who stayed cancer free (HRgood SRH 1.59, 95% CI 1.44-1.77 and HRpoor SRH 3.34, 95% CI 2.91-3.84). Conclusion: Lower SRH at baseline predicted increased cancer risk and all-cause mortality in middle-aged to older women. Poor SRH at baseline predicted all-cause mortality in women who later received a cancer diagnosis. Both good and poor SRH at baseline predicted all-cause mortality in women who stayed cancer-free, and the association was stronger for these women compared to both the entire cohort and to women who were subsequently diagnosed with cancer.
ABSTRACT
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a pregnancy-related condition caused by maternal antibodies binding an alloantigen on fetal platelets. In most cases the alloantigen is formed by a single amino acid, integrin ß3 Leu33, referred to as human platelet antigen-1a (HPA-1a). Production of anti-HPA-1a antibodies likely depends on CD4+ T cells that recognize the same alloantigen in complex with the HLA-DRA/DRB3*01:01 molecule. While this complex is well characterized, T cell recognition of it is not. Here, to examine the nature of antigen recognition by HPA-1a-specific T cells, we assayed native and synthetic variants of the integrin ß3 peptide antigen for binding to DRA/DRB3*01:01-positive antigen-presenting cells and for T cell activation. We found that HPA-1a-specific T cells recognize non-allogeneic integrin ß3 residues anchored to DRA/DRB3*01:01 by the allogeneic Leu33, which itself is not directly recognized by these T cells. Furthermore, these T cell responses are diverse, with different T cells depending on different residues for recognition. This represents a unique form of indirect allorecognition in which a non-allogeneic peptide sequence becomes immunogenic by stable anchoring to MHC by an allogeneic residue.