Skip to main content

Main menu

  • Home
  • Content
    • First Release
    • Current
    • Archives
    • Collections
    • Audiovisual Rheum
    • COVID-19 and Rheumatology
  • Resources
    • Guide for Authors
    • Submit Manuscript
    • Payment
    • Reviewers
    • Advertisers
    • Classified Ads
    • Reprints and Translations
    • Permissions
    • Meetings
    • FAQ
    • Policies
  • Subscribers
    • Subscription Information
    • Purchase Subscription
    • Your Account
    • Terms and Conditions
  • About Us
    • About Us
    • Editorial Board
    • Letter from the Editor
    • Duncan A. Gordon Award
    • Privacy/GDPR Policy
    • Accessibility
  • Contact Us
  • JRheum Supplements
  • Services

User menu

  • My Cart
  • Log In

Search

  • Advanced search
The Journal of Rheumatology
  • JRheum Supplements
  • Services
  • My Cart
  • Log In
The Journal of Rheumatology

Advanced Search

  • Home
  • Content
    • First Release
    • Current
    • Archives
    • Collections
    • Audiovisual Rheum
    • COVID-19 and Rheumatology
  • Resources
    • Guide for Authors
    • Submit Manuscript
    • Payment
    • Reviewers
    • Advertisers
    • Classified Ads
    • Reprints and Translations
    • Permissions
    • Meetings
    • FAQ
    • Policies
  • Subscribers
    • Subscription Information
    • Purchase Subscription
    • Your Account
    • Terms and Conditions
  • About Us
    • About Us
    • Editorial Board
    • Letter from the Editor
    • Duncan A. Gordon Award
    • Privacy/GDPR Policy
    • Accessibility
  • Contact Us
  • Follow jrheum on Twitter
  • Visit jrheum on Facebook
  • Follow jrheum on LinkedIn
  • Follow jrheum on YouTube
  • Follow jrheum on Instagram
  • Follow jrheum on RSS
Research ArticleArticle

Serum Amyloid A and C-Reactive Protein Concentrations Are Differently Associated with Markers of Autoimmunity in Patients with Primary Sjögren’s Syndrome

MARJA PERTOVAARA, JUULIA JYLHÄVÄ, HANNU UUSITALO, JUHANI PUKANDER, HEIKKI HELIN and MIKKO HURME
The Journal of Rheumatology November 2009, 36 (11) 2487-2490; DOI: https://doi.org/10.3899/jrheum.090300
MARJA PERTOVAARA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: marja.pertovaara@uta.fi
JUULIA JYLHÄVÄ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HANNU UUSITALO
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
JUHANI PUKANDER
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HEIKKI HELIN
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MIKKO HURME
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • References
  • PDF
  • eLetters
PreviousNext
Loading

Abstract

Objective. Primary Sjögren’s syndrome (pSS) is an autoimmune disease in which the concentration of the acute-phase protein serum C-reactive protein (CRP) is low. We investigated whether levels of another acute-phase protein, serum amyloid A (SAA), are increased in patients with pSS and whether the immunological markers in patients with pSS are associated with variation in SAA levels.

Methods. Serum SAA concentrations were measured by ELISA in 74 patients with pSS and in 56 control subjects with sicca symptoms.

Results. Median SAA levels did not differ significantly between patients with pSS and subjects with sicca symptoms. In patients with pSS SAA concentrations correlated significantly with age, leukocyte count, CRP, interleukin 6, and C4. Unlike CRP, there was a significant inverse correlation between SAA and serum IgG levels and anti-SSA antibody titers, as well as a trend towards an inverse correlation between SAA and antinuclear antibody and rheumatoid factor titers.

Conclusion. Our data imply that high SAA production could constitute a protective element in pSS: high SAA levels inhibit in particular various signs of B cell hyperreactivity, i.e., IgG and autoantibody production.

  • AUTOANTIBODIES
  • B CELL HYPERREACTIVITY
  • C-REACTIVE PROTEIN
  • IgG
  • PRIMARY SJÖGREN’S SYNDROME
  • SERUM AMYLOID A PROTEIN

Primary Sjögren’s syndrome (pSS) is a chronic rheumatic autoimmune disease, in which an elevated erythrocyte sedimentation rate (ESR), reflecting increased inflammatory activity, is a frequent finding. In contrast, Moutsopoulos and colleagues pointed out in the early 1980s that the concentration of the acute-phase protein serum C-reactive protein (CRP) is usually low in patients with pSS1. Apart from serum CRP, serum amyloid A (SAA) protein is another inflammatory marker involved in the pathogenesis of many diseases of inflammatory nature2. We sought to establish whether SAA concentrations in pSS behave like ESR and are markedly increased, or whether they behave like CRP, with only modest elevations. We measured concentrations of SAA in patients with pSS and, as controls, in patients with sicca symptoms but no pSS.

MATERIALS AND METHODS

Subjects and controls

Serum samples were obtained with informed consent from 74 patients with pSS (72 women, 2 men), and 56 subjects presenting with sicca symptoms (46 women, 10 men) but not fulfilling the criteria for pSS served as controls. The mean age of the patients with pSS was 58 ± 12 years (range 29–82 yrs), and of the subjects with sicca symptoms 55 ± 13 years (range 28–80 yrs). The study protocol was approved by the Ethical Committee of Tampere University Hospital, Tampere, Finland. The data collections of the patients with pSS and controls have been described in detail3,4.

Standard laboratory tests

Rheumatoid factor (RF) was determined by laser nephelometry and antinuclear antibodies (ANA) by indirect immunofluorescence using Hep-2 cells. Anti-SSA and anti-SSB antibodies were determined by enzyme immunoassay and serum concentration of beta-2 microglobulin by radioimmunoassay (Pharmacia beta-2-micro RIA kit, Pharmacia Diagnostics, Uppsala, Sweden).

SAA determinations

Serum SAA concentrations were determined with an ELISA kit with a detection limit of < 0.004 mg/l (Human SAA, Biosource International, Camarillo, CA, USA). The interassay coefficient of variation (CV) was according to the manufacturer 7.8% at a mean level of 0.0613 mg/l and 7.0% at a mean level of 0.5988 mg/l.

Statistical methods

Mann-Whitney U-test was used for comparisons of continuous variables and correlations were calculated with the Spearman correlation coefficient. Findings were considered statistically significant at p < 0.05. Statistical analyses were performed with SPSS 15.0 for Windows.

RESULTS

The clinical characteristics of the patients with pSS are presented in Table 1. The median SAA concentration in these patients was 26.6 mg/l [interquartile range (IQR) 11.8, 55.9] and 21.4 mg/l (IQR 13.7, 40.0) in subjects with sicca symptoms (p = 0.354). The median SAA levels did not differ significantly between female and male subjects.

View this table:
  • View inline
  • View popup
Table 1.

Demographic, clinical, and immunological characteristics of 74 patients with primary Sjögren’s syndrome.

The correlations of serum SAA concentrations with various clinical and immunological manifestations of the patients with pSS are set out in Table 2. To compare, the analogous data are presented also regarding CRP (Table 2).

View this table:
  • View inline
  • View popup
Table 2.

Correlation (r) of serum amyloid A (SAA) and serum C-reactive protein (CRP) with demographic, clinical, and immunological findings in 74 patients with primary Sjögren’s syndrome (Spearman correlation coefficient).

SAA levels were significantly higher in pSS patients with myalgic symptoms compared with those without, and in patients with neurological symptoms compared with those without (Table 3). However, the patients with neurological symptoms were also older than those without (65 vs 56 yrs; p = 0.011). pSS patients with a history of purpura tended to have lower SAA levels than those without (Table 3). Age of pSS patients with myalgic symptoms or purpura did not differ from those without these manifestations (data not shown).

View this table:
  • View inline
  • View popup
Table 3.

Serum amyloid A (SAA) concentrations in 74 patients with primary Sjögren’s syndrome grouped by the presence of various extraglandular manifestations.

DISCUSSION

SAA levels in patients with pSS did not differ from those in subjects of the same age with sicca symptoms but no pSS, but they were approximately twice as high as those we previously observed in healthy young adults6. SAA levels correlated significantly with leukocyte counts, CRP, interleukin 6 (IL-6), and C4. All these findings are biologically plausible: SAA is known to function in the priming of neutrophils2, IL-6 stimulates the production of acute-phase proteins, and elevation in complement C4 concentration reflects an acute-phase reaction. However, there was no association between C4 and CRP.

Interestingly, there was a significant inverse correlation between SAA and serum IgG levels and anti-SSA antibody titers as well as a trend towards an inverse correlation between SAA and ANA and RF titers, but not between CRP and these autoantibodies. Apoptotic defects and impaired clearance of cellular debris are considered key events in the development of autoimmunity7. As levels of SAA correlated inversely with autoantibodies, it would appear that a capacity for high SAA production would protect from the autoimmune response. Support for these findings can be drawn from an experimental study where serum from amyloidotic mice was shown to suppress in vitro the antibody response to sheep red blood cells, and this suppression was removed by absorption of the sera with antiserum to SAA8. SAA has also been reported to have a protective role in vascular injury (as reviewed9). Inflammation is currently considered a link between atherosclerosis and autoimmune diseases10, and CRP and SAA have been associated with cardiovascular risk in the general population11, but no data exist on SAA and this risk in patients with pSS.

It is logical that SAA levels correlated positively with serum alkaline phosphatase, since liver is a major site of SAA synthesis12. The association of SAA levels with neurological symptoms could be due to older age of these patients, but age did not explain the association of SAA levels with myalgia. Low levels of SAA were found to be associated with purpura and low complement C4 levels, manifestations that have been found to be adverse predictors of development of non-Hodgkin lymphoma in pSS13.

In conclusion, analogously to CRP and in contrast with ESR levels, SAA concentrations are only modestly elevated in patients with pSS. Serum SAA and CRP concentrations are differently associated with various markers of autoimmunity in patients with pSS. Our data suggest that high SAA production could constitute a protective element in an autoimmune disease such as pSS: high SAA levels inhibit in particular various signs of B cell hyperreactivity, i.e., IgG and autoantibody production, and moreover protect from the development of hypocomplementemia C4 and purpura, signs linked in previous studies to the development of lymphoma in patients with pSS.

Acknowledgments

We thank Sinikka Repo-Koskinen for skilful technical assistance.

Footnotes

  • Supported by the competitive Funding of Pirkanmaa Hospital District, Tampere, Finland.

    • Accepted for publication June 5, 2009.

REFERENCES

  1. 1.↵
    1. Moutsopoulos HM,
    2. Elkon KB,
    3. Mavridis AK,
    4. Acritidis NC,
    5. Hughes GR,
    6. Pepys MB
    . Serum C-reactive protein in primary Sjögren’s syndrome. Clin Exp Rheumatol 1983;1:57–8.
    OpenUrlPubMed
  2. 2.↵
    1. Uhlar CM,
    2. Whitehead AS
    . Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem 1999;265:501–23.
    OpenUrlPubMed
  3. 3.↵
    1. Pertovaara M,
    2. Korpela M,
    3. Kouri T,
    4. Pasternack A
    . The occurrence of renal involvement in Sjögren’s syndrome: a study of 78 patients. Rheumatology 1999;38:1113–20.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Pertovaara M,
    2. Korpela M,
    3. Uusitalo H,
    4. et al.
    Clinical follow-up study of 87 patients with sicca symptoms (dryness of eyes or mouth, or both). Ann Rheum Dis 1999;58:423–7.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Chisholm DM,
    2. Mason DK
    . Labial salivary gland biopsy in Sjögren’s syndrome. J Clin Pathol 1968;21:656–60.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Jylhava J,
    2. Haarala A,
    3. Eklund C,
    4. et al.
    Serum amyloid A is independently associated with metabolic risk factors but not with early atherosclerosis: the Cardiovascular Risk in Young Finns Study. J Intern Med 2009;266:286–95.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Kravitz MS,
    2. Shoenfeld Y
    . Autoimmunity to protective molecules: is it the perpetuum mobile (vicious cycle) of autoimmune rheumatic diseases. Nat Clin Pract Rheumatol 2006;2:481–90.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Benson MD,
    2. Aldo-Benson MA,
    3. Shirahama T,
    4. Borel Y,
    5. Cohen AS
    . Suppression of in vitro antibody response by a serum factor (SAA) in experimentally induced amyloidosis. J Exp Med 1975;142:236–41.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Sodin-Semrl S,
    2. Zigon P,
    3. Cucnik S,
    4. et al.
    Serum amyloid A in autoimmune thrombosis. Autoimmun Rev 2006;6:21–7.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Abou-Raya A,
    2. Abou-Raya S
    . Inflammation: a pivotal link between autoimmune diseases and atherosclerosis. Autoimmun Rev 2006;5:331–7.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Ridker PM,
    2. Rifai N,
    3. Rose L,
    4. Burling JE,
    5. Cook NR
    . Comparison of C-reactive protein and low–density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002;347:1557–65.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Urieli-Shoval S,
    2. Linke RP,
    3. Matzner Y
    . Expression and function of serum amyloid A, a major acute phase protein, in normal and disease states. Curr Opin Hematol 2000;7:64–9.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Skopouli FN,
    2. Dafni U,
    3. Ioannidis JP,
    4. Moutsopoulos HM
    . Clinical evolution, and morbidity and mortality of primary Sjögren’s syndrome. Semin Arthritis Rheum 2000;29:296–304.
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

The Journal of Rheumatology
Vol. 36, Issue 11
1 Nov 2009
  • Table of Contents
  • Table of Contents (PDF)
  • Index by Author
  • Editorial Board (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Rheumatology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Serum Amyloid A and C-Reactive Protein Concentrations Are Differently Associated with Markers of Autoimmunity in Patients with Primary Sjögren’s Syndrome
(Your Name) has forwarded a page to you from The Journal of Rheumatology
(Your Name) thought you would like to see this page from the The Journal of Rheumatology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Serum Amyloid A and C-Reactive Protein Concentrations Are Differently Associated with Markers of Autoimmunity in Patients with Primary Sjögren’s Syndrome
MARJA PERTOVAARA, JUULIA JYLHÄVÄ, HANNU UUSITALO, JUHANI PUKANDER, HEIKKI HELIN, MIKKO HURME
The Journal of Rheumatology Nov 2009, 36 (11) 2487-2490; DOI: 10.3899/jrheum.090300

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

 Request Permissions

Share
Serum Amyloid A and C-Reactive Protein Concentrations Are Differently Associated with Markers of Autoimmunity in Patients with Primary Sjögren’s Syndrome
MARJA PERTOVAARA, JUULIA JYLHÄVÄ, HANNU UUSITALO, JUHANI PUKANDER, HEIKKI HELIN, MIKKO HURME
The Journal of Rheumatology Nov 2009, 36 (11) 2487-2490; DOI: 10.3899/jrheum.090300
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
    • Abstract
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • Acknowledgments
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • References
  • PDF
  • eLetters

Related Articles

Cited By...

More in this TOC Section

  • Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines Against COVID-19 Infection Among Patients With Systemic Autoimmune Rheumatic Diseases on Immunomodulatory Medications
  • Clinimetric Validation of the Assessment of Spondyloarthritis International Society Health Index in Patients With Radiographic Axial Spondyloarthritis in Ixekizumab Trials
  • Sex-Specific Differences in Patients With Psoriatic Arthritis: A Systematic Review
Show more Articles

Similar Articles

Content

  • First Release
  • Current
  • Archives
  • Collections
  • Audiovisual Rheum
  • COVID-19 and Rheumatology

Resources

  • Guide for Authors
  • Submit Manuscript
  • Author Payment
  • Reviewers
  • Advertisers
  • Classified Ads
  • Reprints and Translations
  • Permissions
  • Meetings
  • FAQ
  • Policies

Subscribers

  • Subscription Information
  • Purchase Subscription
  • Your Account
  • Terms and Conditions

More

  • About Us
  • Contact Us
  • My Alerts
  • My Folders
  • Privacy/GDPR Policy
  • RSS Feeds
The Journal of Rheumatology
The content of this site is intended for health care professionals.
Copyright © 2022 by The Journal of Rheumatology Publishing Co. Ltd.
Print ISSN: 0315-162X; Online ISSN: 1499-2752
Powered by HighWire