Local anti—type ii collagen antibody production in rheumatoid arthritis synovial fluid

Rönnelid, Johan; Lysholm, J; Engström‐Laurent, Anna; Klareskog, Lars; Heyman, Birgitta

doi:10.1002/art.1780370707

Cited by 114 publications

(100 citation statements)

References 42 publications

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“…Both cell frequencies were increased compared with the peripheral population (15-fold and 3-fold, respectively). The numbers we estimated for synovial p-ASC were along the same order of magnitude as those published for synovial ASC (25,26). There was no indication of an association between the presence of HLA-DR4 and the frequency of p-ASC for anti-CII (25).…”

Section: Discussionsupporting

confidence: 60%

“…The numbers we estimated for synovial p-ASC were along the same order of magnitude as those published for synovial ASC (25,26). There was no indication of an association between the presence of HLA-DR4 and the frequency of p-ASC for anti-CII (25). The highest frequency was observed in patient RA7 (14.1% p-ASC for IgG anti-CII), who was typed DR4-.…”

Section: Discussionsupporting

confidence: 57%

“…5). Serum antibodies as well as ASC to this target have been described in RA patients, but again, not without discrepancies concerning their quantities and qualities (5,25,26). In our study, human CII was used to detect antibodies by an ELISA, which works reliably with tissue culture supernatants.…”

Section: Discussionmentioning

confidence: 81%

“…Organized structures resembling germinal centers have been described, which contain follicular dendritic cells and CD4+ T cells and reveal clonal expansion of B cells exhibiting isotype switching and somatic hypermutation (19,22). Numerous plasma cells have been found which produce IgM, IgG, and IgA (24); some of these also secrete RF or antibodies specific for type I1 collagen (CII) (17,(25)(26)(27).…”

mentioning

confidence: 99%

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The B cell repertoire of patients with rheumatoid arthritis. II. Increased frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat‐shock protein 60 or human type II collagen in synovial fluid and tissue

Rudolphi

Rzepka

Batsford

et al. 1997

Arthritis & Rheumatism

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Objective.A qualitative and quantitative analysis of the functional, antigen-specific B cell receptor repertoire of patients with rheumatoid arthritis (RA) in synovial and peripheral compartments.Methods. B cells were activated to grow and differentiate at high efficiency in vitro under limitingdilution conditions. Isotype and specificity of the secreted Ig were tested by enzyme-linked immunosorbent assay.Results. In contrast to peripheral B cells, most synovial B cells had already switched to IgG/IgA in vivo. The frequencies of B cells specifically recognizing foreign antigens were decreased within the synovial population, whereas the frequencies of B cells specific for type I1 collagen, mycobacterial heat-shock protein 60 (hsp60), or IgG Fc fragments were significantly increased, revealing a negative correlation in terms of frequencies.Conclusion. B cells specific for human type I1 collagen, hsp60, and IgG Fc fragments are produced and/or expanded locally within the affected joints of RA patients. Thus, the specific immune system is definitely involved in the local inflammatory and destructive processes.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 81%

mentioning

confidence: 99%

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The B cell repertoire of patients with rheumatoid arthritis. II. Increased frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat‐shock protein 60 or human type II collagen in synovial fluid and tissue

Rudolphi

Rzepka

Batsford

et al. 1997

Arthritis & Rheumatism

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“…Indeed, B cells producing antibodies to type I1 collagen have been detected in SF but rarely in serum (38), and antibodies to type I1 collagen are present in higher levels in SF than serum (30). However, collagen antibodies, in contrast to aggrecan antibodies, do sometimes appear in the circulation and do show disease specificity, being detected more frequently in RA than in other diseases.…”

Section: Discussionmentioning

confidence: 99%

Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases

Karopoulos

Rowley

Ilic

et al. 1996

Arthritis & Rheumatism

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Objective. To investigate the occurrence of IgG antibodies to aggrecan in synovial fluids (SF) from patients with arthritis and various articular diseases, and to determine the nature of epitopes present within aggrecan that react with these antibodies. Methods. SF samples were reacted with native aggrecan, reduced and alkylated aggrecan, chondroitin sulfate, and keratan sulfate, using dot‐blots and a novel enzyme‐linked immunosorbent assay (ELISA). The nature of the epitopes present on aggrecan was elucidated using Western blots and a competitive inhibition ELISA. Results. IgG antibodies to aggrecan were found in >50% of the SF samples tested. No IgG antibody reactivity was observed in serum from the same patients. The antibodies appeared to react predominantly with native aggrecan, and there was no disease specificity. It was shown that the epitopes to these antibodies were located within the N‐terminal region of the core protein. Conclusion. This study demonstrates the frequent occurrence of IgG antibodies to aggrecan in human SF. The major epitope is located in the G1 domain of the aggrecan core protein. These IgG antibodies appear to be produced locally within the synovial cavity, probably in response to various articular diseases, resulting in the loss of native aggrecan from articular cartilage.

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The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256 – 270 glycopeptide to H-2Aq and H-2Ap molecules

et al. 1998

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The Aq major histocompatibility complex (MHC) class II molecule is associated with susceptibility to murine collagen-induced arthritis (CIA), whereas the closely related H-2Ap molecule is not. To understand the molecular basis for this difference, we have analyzed the ability of H-2Aq and H-2Ap molecules (referred to as Aq and Ap) to bind and present collagen type II (CII)-derived glycosylated and non-glycosylated peptides. T cell clones specific for the immunodominant CII 256-270 peptide and restricted to both Aq and Ap molecules were identified. When these clones were incubated with CII protein and either Aq- or Ap-expressing antigen-presenting cells (APC), only Aq-expressing APC were able to induce stimulation. With the use of A(beta) transgenic mice this could be shown to be solely dependent on the MHC class II molecule itself and to be independent of other MHC- or non-MHC genes. Peptide binding studies were performed using affinity-purified MHC class II molecules. The CII 256-270 peptide bound with lower affinity to the Ap molecule than to the Aq molecule. Using a set of alanine-substituted CII 256-270 peptides, MHC class II and T cell receptor (TCR) contacts were identified. Mainly the side chains of isoleucine 260 and phenylalanine 263 were used for binding both the Aq and Ap molecule, i.e. the peptide was orientated similarly in the binding clefts. The major TCR contact amino acids were lysine 264, which can be posttranslationally modified, and glutamic acid 266, which is the only amino acid in the heterologous peptide which differs from the mouse sequence. Glycosylation at positions 264 and 270 of the CII 256-270 peptide did not change the anchor positions used for binding to the Aq or Ap molecules. The autologous form of the peptide (with aspartic acid at position 266) bound with lower affinity to the Aq molecule as compared with the heterologous peptide. The variable affinity displayed by the immunodominant CII 256-270 peptide for different MHC class II molecules, the identification of MHC and TCR contacts and the significance of glycosylation of these have important implications for the understanding of the molecular basis for inherited MHC class II-associated susceptibility to CIA and in turn, for development of novel treatment strategies in this disease.

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Local anti—type ii collagen antibody production in rheumatoid arthritis synovial fluid

Cited by 114 publications

References 42 publications

The B cell repertoire of patients with rheumatoid arthritis. II. Increased frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat‐shock protein 60 or human type II collagen in synovial fluid and tissue

The B cell repertoire of patients with rheumatoid arthritis. II. Increased frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat‐shock protein 60 or human type II collagen in synovial fluid and tissue

Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases

The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256 – 270 glycopeptide to H-2Aq and H-2Ap molecules

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