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Peptidylarginine deiminases (PADs) catalyze citrullination, a post-translational modification playing a pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). The interplay between single nucleotide polymorphisms (SNPs) in the PADI genes and known risk factors for ACPA-positive RA, including smoking, HLA-DR4 and -1, and the PTPN22 R620W polymorphism, was investigated. We typed four PADI2 SNPs, four PADI4 SNPs, and the PTPN22 R620W SNP in 445 Danish RA patients and 533 age-matched healthy controls, as well as in 200 North American RA patients and 100 age- and sex-matched controls. The HLA-DRB1 locus was typed in the Danish cohort. Logistic regression analyses, adjusted for age, sex, smoking status, and PTPN22 R620W, revealed increased risk of anti-CCP-positive RA in carriers of rs11203367(T) (OR: 1.22, p=0.03) and reduced risk in carriers of rs2240335(A) in PADI4 (OR: 0.82, p=0.04). rs74058715(T) in PADI4 conferred reduced risk of anti-CCP-negative RA (OR: 0.38, p=0.003). In HLA-DRB1*04-positive individuals, specifically, the risk of anti-CCP-positive RA was increased by carriage of PADI4 rs1748033(T) (OR: 1.54, p=0.007) and decreased by carriage of PADI4 rs74058715(T) (OR: 0.44, p=0.01), and we observed an interaction between these SNPs and HLA-DRB1*04 (p=0.004 and p=0.008, respectively) Thus, PADI4 polymorphisms associate with ACPA-positive RA, particularly in HLA-DRB1*04-positive individuals, and with ACPA-negative RA independently of HLA-DRB1*04.

Epidemiologic studies have shown associations between periodontitis and rheumatoid arthritis (RA), but a causal relationship has not been established. Citrullination of gingival proteins by human peptidylarginine deiminases (PADs) or PAD from Porphyromonas gingivalis has been proposed to generate autoantigens in anti-CCP-positive RA. This study investigated whether the association between periodontitis and RA is influenced by single nucleotide polymorphisms (SNPs) in the genes encoding PAD2 and PAD4 that catalyze aberrant citrullination in RA and often are overexpressed in inflamed gingival connective tissue in subjects with periodontitis. The study included 137 RA patients and 161 controls with self-reported periodontitis. Periodontitis onset preceded RA onset by 13 years on average and was not associated with any of the SNPs investigated. In subjects with periodontitis, carriage of the minor alleles of rs2057094 and rs2235912 in PADI2 significantly increased the risk of RA (odds ratios 1.42 [p = 0.03] and 1.48 [p = 0.02], respectively), and this effect was driven by the anti-CCP-negative RA patients. The minor alleles of these SNPs only increased risk of anti-CCP-positive RA in individuals with periodontitis and a history of smoking. These data suggest that individuals with periodontitis carrying the minor alleles of SNPs rs2057094, rs2076616 and rs2235912 in PADI2 may be at increased risk of RA.

Abstract Background In 2017 Ploug and Holm argued that anonymizing individuals in the Danish circumcision registry was insufficient to protect these individuals from what they regard as the potential harms of being in the registry (overreaching social pressure, stigmatization, medicalization of a religious practice, discrimination and promoting polarized research). Discussion We argue that Ploug and Holm’s fears in each of the areas are misguided, not supported by the evidence, and could interfere with the gathering of accurate data. The extent of the risks and harms associated with ritual circumcision is not well known. The anonymized personal health data supplemented with the circumcision registry will enable more precise research into the medical consequences of ritual circumcision, and allow parents to make more fully informed decisions about circumcision with minimal, if any, adverse consequences.

BACKGROUND:Blood transfusion is an essential component of a modern healthcare system. Because knowledge about blood donor demography may inform the design of strategies for donor recruitment and retention, we used nationwide registers to characterize the entire population of blood donors in Denmark in 2010. METHODS:The study population comprised all Danes in the age range eligible for blood donation (N = 3,236,753) at the end of 2010. From the Scandinavian Donations and Transfusions (SCANDAT) register, we identified 174,523 persons who donated blood in Danish blood banks at least once in 2010. The association between sociodemographic characteristics and blood donor prevalence was examined using regression models. RESULTS:The overall prevalence of blood donation was 5.4% among both women and men. The age-specific prevalence of blood donation peaked at 25 years of age (6.8%) for women and 30 years of age (5.7%) for men. Children of any age were associated with lower prevalence of blood donation among women, while the opposite was seen for men. Middle to high income groups, but not the highest income group, had fourfold higher donor prevalence than the lowest income group (6.7% compared to 1.7%). The prevalence of blood donation was considerably lower among men living with their parents (2.9%) or alone (3.9%) than among men cohabitating with a woman (6.2%). SUMMARY:Social marginalization, as indicated by low income and being a male living without a woman, was associated with lower prevalence of blood donation. However, individuals with very high incomes and women with children were underrepresented in the Danish blood donor population.

BACKGROUND: Poor self-rated health (SRH) has been connected to immunological changes, and pregnancy complications have been suggested in the etiology of autoimmune diseases including inflammatory bowel disease (IBD). We evaluated the impact of self-rated pre-pregnancy health and pregnancy course, hyperemesis, gestational hypertension, and preeclampsia on risk of IBD. METHODS: Information was collected by questionnaires from The Danish National Birth Cohort (enrolment 1996-2002) at 16(th) and 30(th) week of pregnancy and 6 months postpartum. A total of 55,699 women were followed from childbirth until development of IBD (using validated National Hospital Discharge Register diagnoses), emigration, death, or end of follow-up, 31(st) of October, 2011. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusting for age and evaluating pre-pregnancy BMI, parity, alcohol and tobacco consumption, and socio-occupational status as potential confounders. RESULTS: Risk of IBD increased with decreasing level of self-rated pre-pregnancy health (p = 0.002) and was elevated in women with poor self-rated pregnancy course (HR, 1.61, 95% CI 1.22-2.12). Associations persisted for more than 5 years postpartum. Hyperemesis and preeclampsia were not significantly associated with risk of IBD. CONCLUSIONS: This is the first prospective observational study to suggest that poor self-rated health--in general and in relation to pregnancy--is associated with increased risk of IBD even in the long term though results needs further confirmation. Symptoms of specific pregnancy complications were, on the other hand, not significantly associated with risk of IBD.

Discharge diagnoses following hospital admissions in Denmark are recorded in the Danish National Patient Registry (NPR). Such routine hospitalization records may serve as useful research tools in epidemiological studies. The aim of the study was to provide measures of the validity and completeness of rheumatoid arthritis (RA) diagnoses recorded in the NPR. We identified medical records for 217 patients recorded as having RA in the NPR between 1977 and 2001. Using two definitions of RA (clinically confirmed RA and fulfilment of the American College of Rheumatology (ACR) 1987 diagnostic criteria for RA), a rheumatologist assessed the proportion of RA diagnoses recorded in the NPR that could be confirmed by scrutiny of the original medical records. The completeness of RA diagnoses in the NPR was estimated by a two-sample capture–recapture method. Overall, 59 of the 217 RA diagnoses in the NPR were confirmed by information in the medical records. However, major differences were seen according to characteristics of the underlying hospital registrations. Generally, RA diagnoses were most often confirmed for patients registered as inpatients and for patients with more than one hospital registration with RA. Specifically, only 42 of patients with one RA registration from a rheumatology department were confirmed as having RA. In contrast, 91 of patients treated at a rheumatology department and having three or more hospital registrations with RA were confirmed as having RA. The completeness of the NPR with respect to RA satisfying the ACR 1987 classification criteria was estimated to 26. Our conclusion is that with careful attention to the limitations in the data, discharge diagnoses for patients with records of RA in the Danish NPR can be used for epidemiological research purposes; however, our findings prompt general carefulness when using non-audited registries for research in RA. [ABSTRACT FROM AUTHOR]

Persons with acquired immunodeficiency syndrome (AIDS) have increased risk for non-Hodgkin's lymphoma (NHL). Recent studies have reported the detection of DNA sequences from simian virus 40 (SV40), a macaque polyomavirus that contaminated early poliovirus vaccines, in a large proportion of AIDS-associated NHLs. To examine the association between SV40 exposure and NHL risk, we analyzed data from a U.S. registry-based cohort study of persons with AIDS (1980–96). We calculated NHL incidence in persons born in 1958–61 (exposed to SV40-contaminated poliovirus vaccine as children, n = 39,468) and in 1964–67 (born after vaccines were cleared of SV40 and thus unexposed, n = 17,340). Among persons with AIDS, NHL incidence was 11.7 per 1,000 person-years in SV40-exposed individuals (616 NHL cases) and 10.1 per 1,000 person-years in SV40-unexposed individuals (230 cases; unadjusted relative risk 1.15, 95% CI 0.99–1.34, p = 0.06). Because of differences in cohorts' birth years and the evolving demographics of the AIDS epidemic, SV40-exposed subjects were older at AIDS onset than unexposed subjects (mean age 32.0 vs. 27.2 years, p < 0.0001), and the cohorts differed by sex (p < 0.0001) and ethnic group (p < 0.0001). Since NHL incidence was relatively high among whites (p < 0.0001) and homosexual males (p < 0.0001) and increased with age (p = 0.09), comparisons required adjustments for these factors. After adjustment, SV40 exposure was not associated with NHL incidence (adjusted relative risk 0.97, 95% CI 0.79–1.20, p = 0.80). We conclude that childhood exposure to SV40 through receipt of contaminated poliovirus vaccine was not associated with increased risk for AIDS-associated NHL. Our findings do not support a role for SV40 in lymphomagenesis among immunosuppressed persons. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]