Elsevier

Autoimmunity Reviews

Volume 10, Issue 3, January 2011, Pages 123-125
Autoimmunity Reviews

Review
The meaning of anti-Ro and anti-La antibodies in primary Sjögren's syndrome

https://doi.org/10.1016/j.autrev.2010.09.001Get rights and content

Abstract

Anti-SSA/Ro and anti-La/SSB are the hallmark antibodies in primary Sjögren's syndrome (pSS), being present in 60–70%. These antibodies have been associated with an earlier disease onset, glandular dysfunction and extraglandular manifestations as well as with other B cells activation markers. In addition an immunogenetic background is important for the autoantibody formation, having a stronger association with HLA-DR2 and HLA-DR3. Anti-Ro/SSA and anti-La/SSB antibodies are useful in the diagnosis of pSS and help to identify more “active” patients, however their association with response to treatment is unclear. Herein we review the evidence regarding the association of these antibodies with HLA background, demographic, clinical, glandular dysfunction, other serologic features and response to treatment in patients with pSS.

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

  • Anti-Ro and anti-La antibodies are useful in the diagnosis of primary Sjögren´s Syndrome and help to identify more “active” patients.

  • Specific HLA-II haplotypes are associated with the presence of anti-Ro and anti-La antibodies.

  • Anti-Ro and anti-La antibodies are not serological parameters to assess response to B depleting cells treatment.

References (40)

  • R. Wilson et al.

    Sjögren's syndrome. Influence of multiple HLA-D region alloantigens on clinical and serologic expression

    Arthritis Rheum

    (1984)
  • J. Harley et al.

    Anti-Ro (SSA) and anti-La (SSB) in patients with Sjögren's syndrome

    Arthritis Rheum

    (1986)
  • R. Manthorpe et al.

    Antibodies to SS-B in chronic inflammatory connective tissue diseases: relationship with HLA-Dw2 and HLA-Dw3 antigens in primary Sjögren's syndrome

    Arthritis Rheum

    (1982)
  • J. Harley et al.

    Gene interaction at HLADQ enhances autoantibody production in primary Sjögren's syndrome

    Science

    (1986)
  • M. Rischmueller et al.

    HLA class II phenotype controls diversification of the autoantibody response in primary Sjögren´s syndrome

    Clin Exp Immunology

    (1998)
  • J. Gottenberg et al.

    In primary Sjögren's syndrome, HLA Class II is associated exclusively with autoantibody production and spreading of the autoimmune response

    Arthritis Rheum

    (2003)
  • S. Miyagawa et al.

    Polymorphisms of the HLA class II genes and autoimmune responses to Ro/SSA-La/SSB among Japanese subjects

    Arthritis Rheum

    (1998)
  • P. Guggenbuhl et al.

    Primary Sjögren's syndrome: role of the HLA-DRB1*0301*1501 heterozygotes

    J Rheumatol

    (1998)
  • A. Tzioufas et al.

    Clinical, immunological and immunogenetic aspects of autoantibody production against Ro/SSA, La/SSB and their linear epitopes in primary Sjögren´s syndrome: a European multicentre study

    Ann Rheum Dis

    (2002)
  • M. Ramos-Casals et al.

    Young onset of primary Sjögren's syndrome: clinical and immunological characteristics

    Lupus

    (1998)
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