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Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and rheumatoid arthritis.

Ball RJ, Avenell A, Aucott L, Hanlon P, Vickers MA - Arthritis Res. Ther. (2015)

Bottom Line: Quality assessment found most studies reported acceptable selection criteria but poor descriptions of how cases and controls were recruited.When all studies were included, there was a statistically significant higher seroprevalence of anti-VCA IgG in patients with RA compared to controls with an odds ratio (OR) of 1.61 (95 % confidence interval (CI) 1.05-2.46, p = 0.03), which is a similar-sized summary OR to that reported for systemic lupus erythematosus (SLE).This contrasts with meta-analyses that indicate EBV infection is associated with multiple sclerosis and SLE.

View Article: PubMed Central - PubMed

Affiliation: Health Services Research Unit, Division of Applied Health Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, UK. robert.ball@nhs.net.

ABSTRACT

Introduction: Infection with Epstein-Barr virus (EBV) has been suggested to contribute to the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). We sought to determine whether prior infection with the virus occurs more frequently in patients with RA compared to controls.

Methods: We performed a systematic review and meta-analyses of studies that reported the prevalence of anti-EBV antibodies in the sera of cases with RA and controls by searching Medline and Embase databases from 1946 to 2014, with no language restriction. Mantel-Haenszel odds ratios for the detection of anti-EBV antibodies were calculated, and meta-analyses conducted. Quality assessments were performed using a modified version of the Newcastle-Ottawa scale.

Results: Twenty-three studies were included. Quality assessment found most studies reported acceptable selection criteria but poor descriptions of how cases and controls were recruited. When all studies were included, there was a statistically significant higher seroprevalence of anti-VCA IgG in patients with RA compared to controls with an odds ratio (OR) of 1.61 (95 % confidence interval (CI) 1.05-2.46, p = 0.03), which is a similar-sized summary OR to that reported for systemic lupus erythematosus (SLE). However, when studies were restricted to those reporting more plausible levels of exposure to EBV in the control groups, no significant association was apparent, OR 1.47 (95 % CI 0.88-2.46, p = 0.14). Using anti-EBNA 1 or anti-EA IgG as markers of previous infection also did not yield significant associations (OR 1.05, 95 % CI 0.68-1.61, p = 0.82; OR 2.2, 95 % CI 0.86-5.65, p = 0.10 respectively).

Conclusions: Overall, these findings do not demonstrate an association between EBV seroprevalence and RA and therefore do not support the hypothesis that prior infection with EBV predisposes to the development of RA. This contrasts with meta-analyses that indicate EBV infection is associated with multiple sclerosis and SLE.

No MeSH data available.


Related in: MedlinePlus

Flow chart. Following removal of duplicates, the search produced 2482 abstracts and two articles were identified from references of review articles. Sixty-seven were considered for inclusion and full texts accessed. Forty-four articles were excluded due to a number of the following reasons: no seropositivity values (n = 9); no or inappropriate controls (n = 12); no EBV IgG or IgA data (n = 6); and non-RA data (n = 2). Full results were not available for four articles and authors were contacted for available data, however, there were insufficient data provided in each case and all were excluded. The remaining 23 studies were considered eligible for inclusion and are summarised in Additional file 2. EBV Epstein-Barr virus, Ig immunoglobulin, RA rheumatoid arthritis
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Fig1: Flow chart. Following removal of duplicates, the search produced 2482 abstracts and two articles were identified from references of review articles. Sixty-seven were considered for inclusion and full texts accessed. Forty-four articles were excluded due to a number of the following reasons: no seropositivity values (n = 9); no or inappropriate controls (n = 12); no EBV IgG or IgA data (n = 6); and non-RA data (n = 2). Full results were not available for four articles and authors were contacted for available data, however, there were insufficient data provided in each case and all were excluded. The remaining 23 studies were considered eligible for inclusion and are summarised in Additional file 2. EBV Epstein-Barr virus, Ig immunoglobulin, RA rheumatoid arthritis

Mentions: One reviewer read the abstracts and selected those for full text examination (Fig. 1). Full texts of these articles were read, with those meeting the inclusion criteria considered for data extraction. Authors were contacted when data were not fully available. A selection of 200 abstracts from the Medline search were reviewed by a second reviewer to examine for inter-reviewer variation, with those for which full texts that should be sought and those likely to be eligible for inclusion highlighted.Fig. 1


Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and rheumatoid arthritis.

Ball RJ, Avenell A, Aucott L, Hanlon P, Vickers MA - Arthritis Res. Ther. (2015)

Flow chart. Following removal of duplicates, the search produced 2482 abstracts and two articles were identified from references of review articles. Sixty-seven were considered for inclusion and full texts accessed. Forty-four articles were excluded due to a number of the following reasons: no seropositivity values (n = 9); no or inappropriate controls (n = 12); no EBV IgG or IgA data (n = 6); and non-RA data (n = 2). Full results were not available for four articles and authors were contacted for available data, however, there were insufficient data provided in each case and all were excluded. The remaining 23 studies were considered eligible for inclusion and are summarised in Additional file 2. EBV Epstein-Barr virus, Ig immunoglobulin, RA rheumatoid arthritis
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4587583&req=5

Fig1: Flow chart. Following removal of duplicates, the search produced 2482 abstracts and two articles were identified from references of review articles. Sixty-seven were considered for inclusion and full texts accessed. Forty-four articles were excluded due to a number of the following reasons: no seropositivity values (n = 9); no or inappropriate controls (n = 12); no EBV IgG or IgA data (n = 6); and non-RA data (n = 2). Full results were not available for four articles and authors were contacted for available data, however, there were insufficient data provided in each case and all were excluded. The remaining 23 studies were considered eligible for inclusion and are summarised in Additional file 2. EBV Epstein-Barr virus, Ig immunoglobulin, RA rheumatoid arthritis
Mentions: One reviewer read the abstracts and selected those for full text examination (Fig. 1). Full texts of these articles were read, with those meeting the inclusion criteria considered for data extraction. Authors were contacted when data were not fully available. A selection of 200 abstracts from the Medline search were reviewed by a second reviewer to examine for inter-reviewer variation, with those for which full texts that should be sought and those likely to be eligible for inclusion highlighted.Fig. 1

Bottom Line: Quality assessment found most studies reported acceptable selection criteria but poor descriptions of how cases and controls were recruited.When all studies were included, there was a statistically significant higher seroprevalence of anti-VCA IgG in patients with RA compared to controls with an odds ratio (OR) of 1.61 (95 % confidence interval (CI) 1.05-2.46, p = 0.03), which is a similar-sized summary OR to that reported for systemic lupus erythematosus (SLE).This contrasts with meta-analyses that indicate EBV infection is associated with multiple sclerosis and SLE.

View Article: PubMed Central - PubMed

Affiliation: Health Services Research Unit, Division of Applied Health Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, UK. robert.ball@nhs.net.

ABSTRACT

Introduction: Infection with Epstein-Barr virus (EBV) has been suggested to contribute to the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). We sought to determine whether prior infection with the virus occurs more frequently in patients with RA compared to controls.

Methods: We performed a systematic review and meta-analyses of studies that reported the prevalence of anti-EBV antibodies in the sera of cases with RA and controls by searching Medline and Embase databases from 1946 to 2014, with no language restriction. Mantel-Haenszel odds ratios for the detection of anti-EBV antibodies were calculated, and meta-analyses conducted. Quality assessments were performed using a modified version of the Newcastle-Ottawa scale.

Results: Twenty-three studies were included. Quality assessment found most studies reported acceptable selection criteria but poor descriptions of how cases and controls were recruited. When all studies were included, there was a statistically significant higher seroprevalence of anti-VCA IgG in patients with RA compared to controls with an odds ratio (OR) of 1.61 (95 % confidence interval (CI) 1.05-2.46, p = 0.03), which is a similar-sized summary OR to that reported for systemic lupus erythematosus (SLE). However, when studies were restricted to those reporting more plausible levels of exposure to EBV in the control groups, no significant association was apparent, OR 1.47 (95 % CI 0.88-2.46, p = 0.14). Using anti-EBNA 1 or anti-EA IgG as markers of previous infection also did not yield significant associations (OR 1.05, 95 % CI 0.68-1.61, p = 0.82; OR 2.2, 95 % CI 0.86-5.65, p = 0.10 respectively).

Conclusions: Overall, these findings do not demonstrate an association between EBV seroprevalence and RA and therefore do not support the hypothesis that prior infection with EBV predisposes to the development of RA. This contrasts with meta-analyses that indicate EBV infection is associated with multiple sclerosis and SLE.

No MeSH data available.


Related in: MedlinePlus