ReviewThe meaning of anti-Ro and anti-La antibodies in primary Sjögren's syndrome
Section snippets
Association with HLA class II
Studies to date have showed that levels of anti-Ro/SSA and anti-La/SSB antibodies are higher in HLA-DR3 and HLA-DR2 positive patients [8], [9] Davidson et al., found that DR3 was present in 79% of the Ro/La positive pSS patients comparing with 20% of seronegative group and 25% of controls [7]. In addition, the HLA DR5 has been linked to higher levels of anti-La/SSB antibody [10]. Further, as there is a linkage disequilibrium among DR3 with DQ2, and DR2 with DQ1, both DQ1 and DQ2 have also been
Association with demographic features
Cross sectional studies have shown an earlier disease onset in pSS patients with anti-Ro/SSA and anti-LA/SSB antibodies than in seronegative patients [17], [18]. For instance, patients with younger onset (defined as < 35 years old), presented a higher prevalence (45% vs. 12%) of anti-Ro/SSA antibody than those patients with an elderly onset [17], whereas when groups were defined as > 70 and < 70 years old, the prevalence of antibodies were similar [18]. Regarding the gender, some works have showed
Association with clinical course
Overall, multiple studies have showed that patients with positive results for these antibodies have more frequent parotiditis and extraglandular complications than those with negative results [16], [22], [23], [24]. An analysis of 321 patients with pSS showed that those with organ involvement had in 65% anti-Ro52 and antiRo60 antibodies, whereas the non-organ group had 57%. The occurrence of anti-La/SSB was also greater in the organ-affected group (48% vs. 13% OR 6, 95% CI 3–12) [24].
Finally,
Association with glandular dysfunction
Serum anti-Ro/SSA and anti-La/SSB concentrations have been associated with dry eye symptoms, Shirmer-I test and rose Bengal staining scores [26], [27]. An abnormal sialogram has been also more frequently found in patients with positive anti-Ro antibodies [27]. For instance, Tsuzaka et al. found that the accumulation rate in the parotid glands of patients anti-Ro/SSA was lower than those who had anti-La/SSB antibodies. In addition this rate was significantly lower in patients who were positive
Association with other serologic markers
It is well known the serological abnormalities in patients with pSS such as hypergammaglobulinemia [23], [33], hypocomplementemia [2], [34] as well as high rheumatoid factor (RF), high serum levels of IgG and IgA [7], [9], mixed monoclonal IgM cryoglobulins (found in one third of the patients) [35] and positive ANA titers [9], [36]. Studies have showed that absolute levels of Ro/SSA and La/SSB antibodies correlate with levels of gammaglobulins, β2 microglobulin [37], κ free light chains of
Association with treatment
Recent evidence indicates a major role of B cells in the pathophysiology of pSS. A treatment that eliminates these abnormal B cells (preventing the appearance of extraglandular manifestations and progression toward malignancy) promises as a disease-modifying drug in primary Sjögren's syndrome. Until now, patients enrolled in these trials need to be positive to anti-Ro/SSA antibodies and/or rheumatoid factor [40].Nevertheless, as previously mention the positivity and the titers of anti-Ro/SSA
Conclusion
The anti-Ro/SSA and anti-La/SSB antibodies have a wide-spread occurrence in patients with Sjogren´s Syndrome. Their presence has been associated with glandular and extraglandular manifestations, as well as other features also indicating B cells disturbances. Studies have showed that a specific immunogenetic background is important for anti-Ro/SSA and/or anti-La/SSB autoantibody formation; suggesting that the HLA class II may participate in the perpetuation and initiation of an autoimmune
Take-home messages
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Anti-Ro and anti-La antibodies are useful in the diagnosis of primary Sjögren´s Syndrome and help to identify more “active” patients.
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Specific HLA-II haplotypes are associated with the presence of anti-Ro and anti-La antibodies.
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Anti-Ro and anti-La antibodies are not serological parameters to assess response to B depleting cells treatment.
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