PRF1 mutation alters immune system activation, inflammation, and risk of autoimmunity.

BACKGROUND: Defective alleles within the PRF1 gene, encoding the pore-forming protein perforin, in combination with environmental factors, cause familial type 2 hemophagocytic lymphohistiocytosis (FHL2), a rare, severe autosomal recessive childhood disorder characterized by massive release of cytokines-cytokine storm. OBJECTIVE: The aim of this study was to determine the function of hypomorph PRF1:p.A91V g.72360387 G > A on multiple sclerosis (MS) and type 1 diabetes (T1D). METHODS: We cross-compare the association data for PRF1:p.A91V mutation derived from GWAS on adult MS and pediatric T1D in Sardinians. The novel association with T1D was replicated in metanalysis in 12,584 cases and 17,692 controls from Sardinia, the United Kingdom, and Scotland. To dissect this mutation function, we searched through the coincident association immunophenotypes in additional set of general population Sardinians. RESULTS: We report that PRF1:p.A91V, is associated with increase of lymphocyte levels, especially within the cytotoxic memory T-cells, at general population level with reduced interleukin 7 receptor expression on these cells. The minor allele increased risk of MS, in 2903 cases and 2880 controls from Sardinia p = 2.06 × 10-4, odds ratio OR = 1.29, replicating a previous finding, whereas it protects from T1D p = 1.04 × 10-5, OR = 0.82. CONCLUSION: Our results indicate opposing contributions of the cytotoxic T-cell compartment to MS and T1D pathogenesis.

The narrative-autobiographical approach in the group education of adolescents with diabetes: a qualitative research on its effects.

OBJECTIVE: To introduce a narrative-autobiographical approach in the care and education of adolescents with type-1 diabetes and observe the effects of this novel approach on adolescents' self-awareness, concern for self-care, and well-being. METHODS: Ninety-four adolescents with type-1 diabetes attending one 9-day summer camp in 2004, 2005, or 2006 participated in structured daily self-writing proposals on diabetes, integrated with daily interactive self-management education. After some months, we sent participants interview-like questionnaires, and two independent researchers performed a qualitative analysis of the 50 answers that were mailed back. RESULTS: Writing about the discovery of diabetes was, for many, a stressful experience, but with a strong liberating effect. One relevant point was change, which occurred: (a) in the perception of self; (b) in the relationship with others; (c) in the relationship with the disease. CONCLUSIONS: The integration of autobiography in diabetes camps, by adding the value of sharing individual stories to the liberating power of self-writing, can allow the adolescents to overcome their feelings of diversity, and can initiate several changes reflecting increased self-efficacy, maturity, acceptance of the disease and responsibility in self-management. PRACTICE IMPLICATIONS: Self-writing is feasible and well accepted, and provides healthcare professionals a proper way to patient-centered care.