Ultrasonographic Assessment of Enthesitis in HLA-B27 Positive Patients with Rheumatoid Arthritis, a Matched Case-Only Study
a Matched Case-Only Study. PLoS ONE 8(3): e58616. doi:10.1371/journal.pone.0058616
Ultrasonographic Assessment of Enthesitis in HLA-B27 Positive Patients with Rheumatoid Arthritis, a Matched Case-Only Study
Antonio Mera-Varela 0
Aida Ferreiro-Iglesias 0
Eva Perez-Pampin 0
Marisol Porto-Silva 0
Juan J. Go mez-Reino 0
Antonio Gonzalez 0
Chi Zhang, University of Texas Southwestern Medical Center, United States of America
0 1 Research Laboratory 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria - Hospital Clinico Universitario de Santiago , Santiago de Compostela , Spain , 2 Department of Medicine, University of Santiago de Compostela , Santiago de Compostela , Spain
Introduction: HLA-B27 has a modifier effect on the phenotype of multiple diseases, both associated and non-associated with it. Among these effects, an increased frequency of clinical enthesitis in patients with Rheumatoid Arthritis (RA) has been reported but never explored again. We aimed to replicate this study with a sensitive and quantitative assessment of enthesitis by using standardized ultrasonography (US). Methods: The Madrid Sonography Enthesitis Index (MASEI) was applied to the US assessment of 41 HLA-B27 positive and 41 matched HLA-B27 negative patients with longstanding RA. Clinical characteristics including explorations aimed to evaluate spondyloarthrtitis and laboratory tests were also done. Results: A significant degree of abnormalities in the entheses of the patients with RA were found, but the MASEI values, and each of its components including the Doppler signal, were similar in HLA-B27 positive and negative patients. An increase of the MASEI scores with age was identified. Differences in two clinical features were found: a lower prevalence of rheumatoid factor and a more common story of low back pain in the HLA-B27 positive patients than in the negative. The latter was accompanied by radiographic sacroiliitis in two HLA-B27 positive patients. No other differences were detected. Conclusion: We have found that HLA-B27 positive patients with RA do not have more enthesitis as assessed with US than the patients lacking this HLA allele. However, HLA-B27 could be shaping the RA phenotype towards RF seronegativity and axial involvement.
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Funding: The study was supported by grants 10CSA918040PR from the Xunta de Galicia (http://www.sergas.e/MostrarContidos_N3_T01.aspx?IdPaxina = 10142)
and PI08/0744 of the Instituto de Salud Carlos III (http://www.isciii.es/) that are partially financed by the European Regional Development Fund of the European
Union. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Research in the genetic component of RA etiology has
experienced a marked progress in recent years with the
identification of a large number of susceptibility loci [1,2].
However, there are still many unsolved questions. Among them
the relative to genotype-phenotype relationships are very
prominent. It is expected that genotypes will have an important role in
shaping the RA phenotype and that identification of these
relationships will help manage patients in a personalized manner.
The most established relationship has been the observed between
a large number of RA susceptibility factors and the production of
anti-citrullinated protein antibodies (ACPA). The earlier
discovered association of the shared epitope (SE) with severe RA,
including progression of erosive arthritis, seems to be explained by
SE association with ACPA production. Other lines of active
research in this field include the search for genetic factors
modifying progression of erosions [3,4], or response to treatment
[5,6] and of loci associated with ACPA negative patients [7,8].
Some of these studies are focused in RA susceptibility loci [4,6,8],
which are good candidates because of their involvement in the
disease mechanisms. Additional candidates are the genetic factors
associated with related diseases. These loci are also of known
functional relevance and they have the potential of being involved
in subgroups of RA patients sharing clinical characteristics with
the disease where the loci were identified.
One of these candidates is HLA-B27 [9,10,11,12,13]. It is
strongly associated with ankylosing spondylitis (AS) and with other
spondyloarthritis (SpA), but not with RA [14,15]. HLA-B27 has
also modifier effects on the phenotype that have been observed in
its associated diseases and in some non-HLA-B27 associated
diseases. Among the HLA-B27 associated diseases, there are
multiple reports showing earlier disease onset, more involvement
of sacroiliac and spine joints, a higher tendency to chronicity and
more prevalence of back pain in HLA-B27 positive than in
negative patients [16,17,18,19,20,21]. In addition, non-HLA-B27
associated diseases can be modified to show higher prevalence of
archetypical AS cl (...truncated)