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Separate and overlapping specificities in rheumatoid arthritis antibodies binding to citrulline- and homocitrulline-containing peptides related to type I and II collagen telopeptides.

Turunen S, Hannonen P, Koivula MK, Risteli L, Risteli J - Arthritis Res. Ther. (2015)

Bottom Line: Antibodies to both citrulline and homocitrulline containing type I and II collagen telopeptides can be found in sera of RA patients.These antibodies are not constant from one RA patient to another, but contain separate or overlapping specificities within the same peptide sequence varying between individuals.Our results suggest some relationship between citrulline and homocitrulline-recognizing antibodies, since homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP and anti-MCV.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland. sanna.turunen@oulu.fi.

ABSTRACT

Introduction: Our objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence.

Methods: A total of 72 RA and 72 control sera were analyzed for binding using enzyme-linked immunosorbent assay to citrulline- or homocitrulline-containing type I and II collagen carboxyterminal telopeptides, as well as to cyclic citrullinated peptide (CCP) and to mutated citrullinated vimentin (MCV). Specificities of the antibodies were tested using inhibition-ELISA.

Results: Of the RA sera, 39 (54%) and 41 (57%) were positive for binding to CCP and MCV, respectively. Further, 34 (47%) and 30 (42%) of the patients had specific antibodies binding to and being inhibited by citrulline-containing type I collagen telopeptides and by citrulline-containing type II collagen carboxyterminal telopeptides, respectively. The corresponding figures regarding homocitrulline-containing type I and homocitrulline-containing type II collagen telopeptides were 16 (22%) and 14 (19%). Most of the patients, who were seropositive for citrullinated peptides, showed binding in multiple assays. A total of 10 (14%) RA patients were positive for all the tested peptide pairs, while 28 (39%) of them had antibodies that contained overlapping specifities between citrulline and homocitrulline in the same peptide sequence.

Conclusions: Antibodies to both citrulline and homocitrulline containing type I and II collagen telopeptides can be found in sera of RA patients. These antibodies are not constant from one RA patient to another, but contain separate or overlapping specificities within the same peptide sequence varying between individuals. Our results suggest some relationship between citrulline and homocitrulline-recognizing antibodies, since homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP and anti-MCV.

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Illustration of the specific binding (inhibition-%) in RA patients (n = 72) and in controls (n = 72). Mean is shown as a solid line and ± 2SD is shown by dotted lines. For abbreviations, see Table 1. RA, rheumatoid arthritis; SD, standard deviation.
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Fig1: Illustration of the specific binding (inhibition-%) in RA patients (n = 72) and in controls (n = 72). Mean is shown as a solid line and ± 2SD is shown by dotted lines. For abbreviations, see Table 1. RA, rheumatoid arthritis; SD, standard deviation.

Mentions: Patients with RA were found to have antibodies that bind to citrulline and homocitrulline-containing sequences related to type I and II collagen telopeptides (Figures 1 and 2). These antibodies were rare in healthy individuals (4% to 5% of the controls) and in hemodialysis patients (data not shown). The differences between patients and controls were statistically significant for all assays (Table 3).Figure 1


Separate and overlapping specificities in rheumatoid arthritis antibodies binding to citrulline- and homocitrulline-containing peptides related to type I and II collagen telopeptides.

Turunen S, Hannonen P, Koivula MK, Risteli L, Risteli J - Arthritis Res. Ther. (2015)

Illustration of the specific binding (inhibition-%) in RA patients (n = 72) and in controls (n = 72). Mean is shown as a solid line and ± 2SD is shown by dotted lines. For abbreviations, see Table 1. RA, rheumatoid arthritis; SD, standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4320812&req=5

Fig1: Illustration of the specific binding (inhibition-%) in RA patients (n = 72) and in controls (n = 72). Mean is shown as a solid line and ± 2SD is shown by dotted lines. For abbreviations, see Table 1. RA, rheumatoid arthritis; SD, standard deviation.
Mentions: Patients with RA were found to have antibodies that bind to citrulline and homocitrulline-containing sequences related to type I and II collagen telopeptides (Figures 1 and 2). These antibodies were rare in healthy individuals (4% to 5% of the controls) and in hemodialysis patients (data not shown). The differences between patients and controls were statistically significant for all assays (Table 3).Figure 1

Bottom Line: Antibodies to both citrulline and homocitrulline containing type I and II collagen telopeptides can be found in sera of RA patients.These antibodies are not constant from one RA patient to another, but contain separate or overlapping specificities within the same peptide sequence varying between individuals.Our results suggest some relationship between citrulline and homocitrulline-recognizing antibodies, since homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP and anti-MCV.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland. sanna.turunen@oulu.fi.

ABSTRACT

Introduction: Our objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence.

Methods: A total of 72 RA and 72 control sera were analyzed for binding using enzyme-linked immunosorbent assay to citrulline- or homocitrulline-containing type I and II collagen carboxyterminal telopeptides, as well as to cyclic citrullinated peptide (CCP) and to mutated citrullinated vimentin (MCV). Specificities of the antibodies were tested using inhibition-ELISA.

Results: Of the RA sera, 39 (54%) and 41 (57%) were positive for binding to CCP and MCV, respectively. Further, 34 (47%) and 30 (42%) of the patients had specific antibodies binding to and being inhibited by citrulline-containing type I collagen telopeptides and by citrulline-containing type II collagen carboxyterminal telopeptides, respectively. The corresponding figures regarding homocitrulline-containing type I and homocitrulline-containing type II collagen telopeptides were 16 (22%) and 14 (19%). Most of the patients, who were seropositive for citrullinated peptides, showed binding in multiple assays. A total of 10 (14%) RA patients were positive for all the tested peptide pairs, while 28 (39%) of them had antibodies that contained overlapping specifities between citrulline and homocitrulline in the same peptide sequence.

Conclusions: Antibodies to both citrulline and homocitrulline containing type I and II collagen telopeptides can be found in sera of RA patients. These antibodies are not constant from one RA patient to another, but contain separate or overlapping specificities within the same peptide sequence varying between individuals. Our results suggest some relationship between citrulline and homocitrulline-recognizing antibodies, since homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP and anti-MCV.

Show MeSH
Related in: MedlinePlus