Associations Between Self-Rated Health and Mortality in the Norwegian Women and Cancer (NOWAC) Study.

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.

T cell responses to human platelet antigen-1a involve a unique form of indirect allorecognition.

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.