Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities.
Summary of "Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities."
OBJECTIVE:
/st> Anti-citrullinated protein antibodies (ACPA) and anti-cyclic citrullinated peptide (anti-CCP) antibodies are a hallmark of rheumatoid arthritis and are believed to play a role in disease pathogenesis. These antibodies are typically detected in ELISA with citrullinated peptides (eg, CCP2) or proteins as antigens. The absolute concentration of anti-CCP antibodies in serum is unknown. Although antibodies to several citrullinated proteins can mainly be detected within anti-CCP-positive sera, it is currently unknown whether anti-CCP antibodies are in fact ACPA. Likewise, it is unknown to what extent antibody responses to different citrullinated antigens are crossreactive.
METHODS:
/st> An affinity purification method was established in which citrullinated antigen-specific antibodies were eluted from ELISA plates and then used for detection of other citrullinated antigens in ELISA or western blot. For additional crossreactivity studies, ELISA-based inhibition assays were performed with citrullinated or control peptides as inhibitors.
RESULTS:
/st> The concentration of anti-CCP IgG antibodies was estimated to be at least 30 mug/ml in patients with high anti-CCP levels (>1600 mug/ml). Affinity-purified anti-CCP antibodies were able to recognise citrullinated fibrinogen (cit-fib) and citrullinated myelin basic protein (cit-MBP) on western blot. Furthermore, antibodies specific for cit-fib and cit-MBP were crossreactive. However, additional crossreactivity studies indicated that non-overlapping antibody responses to citrullinated peptides can also exist in patients.
CONCLUSIONS:
/st> This report shows for the first time that anti-CCP antibodies recognise multiple citrullinated proteins and are thus a collection of ACPA. More importantly, the data indicate that different ACPA responses are crossreactive, but that crossreactivity is not complete, as distinct non-crossreactive responses can also be detected in patients with RA.
Affiliation
1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Journal Details
This article was published in the following journal.
Name: Annals of the rheumatic diseases
ISSN: 1468-2060
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20736390
- DOI: http://dx.doi.org/10.1136/ard.2010.131102
Medical and Biotech [MESH] Definitions
Peptides, Cyclic
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Antibodies, Anti-idiotypic
Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.
Anti-inflammatory Agents, Non-steroidal
Anti-inflammatory agents that are not steroids. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They are used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Certain NSAIDs also may inhibit lipoxygenase enzymes or TYPE C PHOSPHOLIPASES or may modulate T-cell function. (AMA Drug Evaluations Annual, 1994, p 1814-5)
Immunoprecipitation
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
Limbic Encephalitis
A paraneoplastic syndrome marked by degeneration of neurons in the medial temporal lobe. Clinical features include behavioral changes, HALLUCINATIONS, loss of short term memory, anosmia, AGEUSIA, and DEMENTIA. Circulating anti-neuronal antibodies (anti-Hu; also called ANNA 1) and small cell lung carcinomas are frequently associated with this condition. (From Pathologe 1997 Sep;18(5):406-10; J Int Neuropsychol Soc 1996 Sep;2(5):460-6; Brain 1997 Jun;120(Pt 6):923-8)
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