The Association Between Gastro-Oesophageal Reflux Disease and Subsequent Rheumatoid Arthritis Occurrence: A Nested Case–Control Study From Taiwan

Objective Gastro-oesophageal reflux disease (GORD) is a common comorbidity among patients with rheumatoid arthritis (RA). While GORD has been attributed to the antirheumatic medications, no studies of human cohorts have investigated a link between GORD and RA. This study investigates whether GORD is associated with a subsequent RA diagnosis over a 5-year follow-up using a population-based dataset. Setting Taiwan Participants We used data from the Taiwan Longitudinal Health Insurance Database. The study group consisted of 13 645 patients with an ambulatory claim showing a GORD diagnosis. We used propensity score matching to select 13 645 comparison patients (one per study patient with GORD). Intervention We tracked each patient’s claims over a 5-year period to identify those who subsequently received a diagnosis of RA. Cox proportional hazard (PH) regression modelling was used for analysis. Results Over 5-year follow-up, RA incidence rate per 1000 person-years was 2.81 among patients with GORD and 0.84 among the comparison group. Cox PH modelling showed that GORD was independently associated with a 2.84-fold increased risk of RA (95% CI 2.09 to 3.85) over 5-year follow-up, after adjusting for the number of ambulatory care visits within the year following the index date (to mitigate surveillance bias). Conclusions We observed that GORD might associate with subsequent RA occurrence. Because current treatment guidelines for RA emphasise early diagnosis and prompt treatment, the observed association between GORD and RA may help acquaint clinicians to patients with GORD with higher RA risk and facilitate early diagnosis and treatment. Objective Gastro-oesophageal reflux disease (GORD) is a common comorbidity among patients with rheumatoid arthritis (RA). While GORD has been attributed to the antirheumatic medications, no studies of human cohorts have investigated a link between GORD and RA. This study investigates whether GORD is associated with a subsequent RA diagnosis over a 5-year follow-up using a population-based dataset. Setting Taiwan Participants We used data from the Taiwan Longitudinal Health Insurance Database. The study group consisted of 13 645 patients with an ambulatory claim showing a GORD diagnosis. We used propensity score matching to select 13 645 comparison patients (one per study patient with GORD). Intervention We tracked each patient’s claims over a 5-year period to identify those who subsequently received a diagnosis of RA. Cox proportional hazard (PH) regression modelling was used for analysis. Results Over 5-year follow-up, RA incidence rate per 1000 person-years was 2.81 among patients with GORD and 0.84 among the comparison group. Cox PH modelling showed that GORD was independently associated with a 2.84-fold increased risk of RA (95% CI 2.09 to 3.85) over 5-year follow-up, after adjusting for the number of ambulatory care visits within the year following the index date (to mitigate surveillance bias). Conclusions We observed that GORD might associate with subsequent RA occurrence. Because current treatment guidelines for RA emphasise early diagnosis and prompt treatment, the observed association between GORD and RA may help acquaint clinicians to patients with GORD with higher RA risk and facilitate early diagnosis and treatmen

RNA-binding activity of hepatitis delta antigen involves two arginine-rich motifs and is required for hepatitis delta virus RNA replication.

Hepatitis delta antigen (HDAg) is an RNA-binding protein with binding specificity for hepatitis delta virus (HDV) RNA (J. H. Lin, M. F. Chang, S. C. Baker, S. Govindarajan, and M. M. C. Lai, J. Virol. 64:4051-4058, 1990). By amino acid sequence homology search, we have identified within its RNA-binding domain two stretches of an arginine-rich motif (ARM), which is present in many prokaryotic and eukaryotic RNA-binding proteins. The first one is KERQDHRRRKA and the second is EDEKRERRIAG, and they are separated by 29 amino acids. Deletion of either one of these ARM sequences resulted in the total loss of the in vitro RNA-binding activity of HDAg. Thus, HDAg is different from other RNA-binding proteins in that it requires two ARM-like sequences for its RNA-binding activity. Replacement of the spacer sequence between the two ARMs with a shorter stretch of sequence also reduced RNA binding in vitro. Furthermore, site-specific mutations of the basic amino acid residues in both ARMs resulted in the total loss or reduction of RNA-binding activity. The biological significance of the RNA-binding activity was studied by examining the trans-activating activity of the RNA-binding mutants. The plasmids expressing HDAgs with various mutations in the RNA-binding motifs were cotransfected with a replication-defective HDV dimer cDNA construct into COS cells. It was found that all the HDAg mutants which had lost the in vitro RNA-binding activity also lost the ability to complement the defect of HDV RNA replication. We conclude that the trans-activating function of HDAg requires its binding to HDV RNA

Histone H1e Interacts with Small Hepatitis Delta Antigen and Affects Hepatitis Delta Virus Replication

Hepatitis delta virus (HDV) encodes two isoforms of delta antigens (HDAgs ). The small form of HDAg (SHDAg) is required for HDV RNA replication, while the large form of HDAg ( LHDAg) is required for viral assembly. Using tandem affinity purification method combined with mass spectrometry, we found that linker histone H1e bound to SHDAg. The binding domain of SHDAg to histone H1e was mapped to the N-terminal 67 amino acids. Oligomerization of SHDAg was required for its interaction with historic H1 e. LHDAg barely bound to histone H1e and was masked at N-terminus. The binding domain of histone H1e to SHDAg was mapped to its central globular domain. HDV replication was inhibited by N- or C-terminal deletion mutants of historic H1e and was rescued by wild- type histone H1e. We conclude that histone H1e plays a significant role in HDV replication through forming protein complex with SHDAg