Precipitable Immune Complexes in Serum and Synovial Fluid of Patients with Rheumatoid Arthritis

IntroductionIndividual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.MethodsWe have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.ResultsThe majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.ConclusionsOur data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.

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Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins

Arthritis Research & Therapy ◽

10.1186/ar3070 ◽

2010 ◽

Vol 12 (4) ◽

pp. R132 ◽

Cited By ~ 55

Author(s):

Katleen Van Steendam ◽

Kelly Tilleman ◽

Marlies De Ceuleneer ◽

Filip De Keyser ◽

Dirk Elewaut ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Immune Complexes ◽

Citrullinated Proteins ◽

Citrullinated Vimentin

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Composition and biological behaviour of immune complexes isolated from synovial fluid of patients with juvenile rheumatoid arthritis (JRA)

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.1995.tb03731.x ◽

2008 ◽

Vol 100 (3) ◽

pp. 514-518 ◽

Cited By ~ 13

Author(s):

J. N. JARVIS ◽

M. M. DIEBOLD ◽

M. K. CHADWELL ◽

M. IOBIDZE ◽

H. T. MOORE

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Juvenile Rheumatoid Arthritis ◽

Immune Complexes ◽

Biological Behaviour

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FRI0085 Number of peptide-specific anti-citrullinated peptide antibodies in synovial fluid and in synovial fluid immune complexes associate with degree of radiological destruction and response to triamcinolone hexacetonide for knee synovitis in rheumatoid arthritis

10.1136/annrheumdis-2017-eular.3222 ◽

2017 ◽

Author(s):

A Sohrabian ◽

L Mathsson Alm ◽

M Hansson ◽

J Lysholm ◽

M Cornillet ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Immune Complexes ◽

Triamcinolone Hexacetonide ◽

Citrullinated Peptide ◽

Peptide Antibodies

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Fcγ receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.142091 ◽

2011 ◽

Vol 70 (6) ◽

pp. 1052-1059 ◽

Cited By ~ 62

Author(s):

Lætitia Laurent ◽

Cyril Clavel ◽

Olivia Lemaire ◽

Florence Anquetil ◽

Martin Cornillet ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Immune Complexes ◽

Cell Types ◽

Biological Data ◽

Fcγ Receptor ◽

Necrosis Factor Alpha ◽

Monocytes And Macrophages ◽

Citrullinated Proteins ◽

Factor Alpha

ObjectiveTo analyse Fcγ receptor (FcγR) expression on monocytes and macrophages from rheumatoid arthritis (RA) patients versus healthy controls (HC), and to compare their responses to immune complexes containing RA-specific anti-citrullinated proteins auto antibodies (ACPA).MethodsMonocytes and monocyte-derived macrophages were obtained from the peripheral blood of 34 RA patients and 69 HC. FcγR expression was studied by flow cytometry. Cells were stimulated with ACPA-containing immune complexes, and tumour necrosis factor alpha (TNFα) was assayed in culture supernatants.ResultsVariations distinguished RA from HC monocytes, corresponding to a 5% and 6% decrease in the percentages of monocytes expressing FcγRI and FcγRII, respectively, and a 7% increase in the proportion of FcγRIII-positive monocytes. Although in both HC and RA patients macrophage differentiation was accompanied by a dramatic increase in the percentage of FcγRIII-expressing cells (72% vs 74.5%), the parallel decline in the proportion of FcγRI-positive cells was markedly smaller in RA (7% vs 43%). Monocytes and macrophages from patients were responsive to ACPA-containing immune complexes but TNFα production in both cell types neither differed from that observed with the corresponding cells from HC, nor correlated with FcγR expression or clinical or biological data. In RA as in HC, ACPA-containing immune complexes induced secretions of more TNFα in macrophages than in paired monocytes (ninefold). Finally, the proinflammatory potential of ACPA-containing immune complexes was confirmed in CD14-positive monocyte macrophages from the synovial fluid of four RA patients.ConclusionsACPA-containing immune complexes induce TNFα secretion by blood and synovial fluid-derived macrophages from RA patients, fitting with their probable involvement in RA pathophysiology.

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IgE-containing immune complexes in synovial fluid of patients with rheumatoid arthritis

Clinical Rheumatology ◽

10.1007/bf02031965 ◽

1990 ◽

Vol 9 (2) ◽

pp. 176-181 ◽

Cited By ~ 6

Author(s):

L. S. De Clerck ◽

N. J. Struyf ◽

C. H. Bridts ◽

F. C. Breedveld ◽

M. L. Westedt ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Immune Complexes

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Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis Patients

Journal of Medical Biochemistry ◽

10.2478/v10011-009-0016-9 ◽

2009 ◽

Vol 28 (3) ◽

pp. 166-171 ◽

Cited By ~ 3

Author(s):

Zoran Mijušković ◽

Ljiljana Rackov ◽

Janko Pejović ◽

Sandra Živanović ◽

Jelica Stojanović ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Disease Activity ◽

Immune Complexes ◽

Biological Fluids ◽

Statistical Significance ◽

Control Group ◽

Laboratory Diagnostics ◽

Complement Components ◽

Effector Mechanisms

Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis PatientsRheumatoid arthritis (RA) is predominantly an intraarticular inflammatory and autoimmune disease that involves different autoantibodies and effector mechanisms. The aim of the study was to determine the utility of Circulating Immune Complexes (CIC) and complement components (C3c, C4) as possible markers for the disease activity in laboratory diagnostics. In a cross-section study 59 patients, according to the clinical criteria, were categorized into two groups: group with moderate (MA, n=24), and group with severe activity (SA, n=35) of RA. The concentration of CIC, C3c and C4 in sera (S) and synovial fluids (SF) was examined by an immunonephelometric method in both groups and compared with values in the control group (n=15) of patients with lesions of the menisci. Obtained results showed that there was no statistical significance in the values of C3c and C4, in both biological fluids, among all tested groups. Significant differences were found in the levels of CIC in both fluids, while testing the parameters (× ± SD, IU/mL) in the sera of groups with SA and MA of RA: 7.43 ± 13.40; 3.01 ± 2.92 (p<0.05) and SF: 13.47 ± 21.1, 5.33 ± 7.53 (p<0.001), respectively. These differences were higher between the group with SA and CG. Results for the concentrations of CIC were significantly higher in SF compared to sera: in the RA group with SA by 77% and group with MA by about 82%. These data could provide a confirmation of the hypothesis about local, intraarticular autoantibodies and subsequent CIC production. It can be concluded that the examination of CIC concentration in serum, and where it is possible in SF, is a useful marker of disease activity in RA patients, in contrast to the tested components of the complement. This statement does not exclude their consumption within immune effector mechanisms, but elicits the possibility that lower molecular fragments (C3d, C4d), as well as the novel activation products, could be better disease activity markers in RA patients.

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