Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis

Søren Jacobsen; Peter Garred; Hans Ole Madsen; Niels H H Heegaard; Merete Lund Hetland; Kristian Stengaard-Pedersen; Peter Junker; Tine Lottenburger; Torkel Ellingsen; Lis Smedegaard Andersen; Ib Hansen; Henrik Skjødt; Jens Kristian Pedersen; Ulrik Birk Lauridsen; Anders J Svendsen; Ulrik Tarp; Jan Pødenphant; Hanne Lindegaard; Aage Vestergaard; Mikkel Østergaard; Kim Hørslev-Petersen; Søren Jacobsen; Peter Garred; Hans Ole Madsen; Niels H H Heegaard; Merete Lund Hetland; Kristian Stengaard-Pedersen; Peter Junker; Tine Lottenburger; Torkel Ellingsen; Lis Smedegaard Andersen; Ib Hansen; Henrik Skjødt; Jens Kristian Pedersen; Ulrik Birk Lauridsen; Anders J Svendsen; Ulrik Tarp; Jan Pødenphant; Hanne Lindegaard; Aage Vestergaard; Mikkel Østergaard; Kim Hørslev-Petersen

doi:10.3899/jrheum.080846

Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis

Søren Jacobsen, Peter Garred, Hans Ole Madsen, Niels H H Heegaard, Merete Lund Hetland, Kristian Stengaard-Pedersen, Peter Junker, Tine Lottenburger, Torkel Ellingsen, Lis Smedegaard Andersen, Ib Hansen, Henrik Skjødt, Jens Kristian Pedersen, Ulrik Birk Lauridsen, Anders J Svendsen, Ulrik Tarp, Jan Pødenphant, Hanne Lindegaard, Aage Vestergaard, Mikkel ØstergaardKim Hørslev-Petersen, Søren Jacobsen, Peter Garred, Hans Ole Madsen, Niels H H Heegaard, Merete Lund Hetland, Kristian Stengaard-Pedersen, Peter Junker, Tine Lottenburger, Torkel Ellingsen, Lis Smedegaard Andersen, Ib Hansen, Henrik Skjødt, Jens Kristian Pedersen, Ulrik Birk Lauridsen, Anders J Svendsen, Ulrik Tarp, Jan Pødenphant, Hanne Lindegaard, Aage Vestergaard, Mikkel Østergaard, Kim Hørslev-Petersen

18 Citations (Scopus)

Abstract

OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2 high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p=0.02), and physical disability by HAQ (p=0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs. CONCLUSION: The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.

Original language	English
Journal	Journal of Rheumatology
Volume	36
Issue number	4
Pages (from-to)	731-5
Number of pages	5
ISSN	0315-162X
DOIs	https://doi.org/10.3899/jrheum.080846 https://doi.org/10.3899/jrheum.080846
Publication status	Published - 1 Apr 2009

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Jacobsen, S., Garred, P., Madsen, H. O., Heegaard, N. H. H., Hetland, M. L., Stengaard-Pedersen, K., Junker, P., Lottenburger, T., Ellingsen, T., Smedegaard Andersen, L., Hansen, I., Skjødt, H., Pedersen, J. K., Lauridsen, U. B., Svendsen, A. J., Tarp, U., Pødenphant, J., Lindegaard, H., Vestergaard, A., ... Hørslev-Petersen, K. (2009). Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis. Journal of Rheumatology, 36(4), 731-5. https://doi.org/10.3899/jrheum.080846, https://doi.org/10.3899/jrheum.080846

Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis. / Jacobsen, Søren ; Garred, Peter; Madsen, Hans Ole et al.

In: Journal of Rheumatology, Vol. 36, No. 4, 01.04.2009, p. 731-5.

Research output: Contribution to journal › Journal article › Research › peer-review

Jacobsen, S , Garred, P, Madsen, HO, Heegaard, NHH, Hetland, ML, Stengaard-Pedersen, K, Junker, P, Lottenburger, T, Ellingsen, T, Smedegaard Andersen, L, Hansen, I, Skjødt, H, Pedersen, JK, Lauridsen, UB, Svendsen, AJ, Tarp, U, Pødenphant, J, Lindegaard, H, Vestergaard, A, Østergaard, M, Hørslev-Petersen, K, Jacobsen, S , Garred, P, Madsen, HO, Heegaard, NHH, Hetland, ML, Stengaard-Pedersen, K, Junker, P, Lottenburger, T, Ellingsen, T, Smedegaard Andersen, L, Hansen, I, Skjødt, H, Pedersen, JK, Lauridsen, UB, Svendsen, AJ, Tarp, U, Pødenphant, J, Lindegaard, H, Vestergaard, A, Østergaard, M & Hørslev-Petersen, K 2009, 'Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis', Journal of Rheumatology, vol. 36, no. 4, pp. 731-5. https://doi.org/10.3899/jrheum.080846, https://doi.org/10.3899/jrheum.080846

Jacobsen S , Garred P, Madsen HO, Heegaard NHH, Hetland ML, Stengaard-Pedersen K et al. Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis. Journal of Rheumatology. 2009 Apr 1;36(4):731-5. doi: 10.3899/jrheum.080846, http://dx.doi.org/10.3899/jrheum.080846

@article{08e72e00b50011df825b000ea68e967b,

title = "Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis",

abstract = "OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2 high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p=0.02), and physical disability by HAQ (p=0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs. CONCLUSION: The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.",

author = "S{\o}ren Jacobsen and Peter Garred and Madsen, {Hans Ole} and Heegaard, {Niels H H} and Hetland, {Merete Lund} and Kristian Stengaard-Pedersen and Peter Junker and Tine Lottenburger and Torkel Ellingsen and {Smedegaard Andersen}, Lis and Ib Hansen and Henrik Skj{\o}dt and Pedersen, {Jens Kristian} and Lauridsen, {Ulrik Birk} and Svendsen, {Anders J} and Ulrik Tarp and Jan P{\o}denphant and Hanne Lindegaard and Aage Vestergaard and Mikkel {\O}stergaard and Kim H{\o}rslev-Petersen and S{\o}ren Jacobsen and Peter Garred and Madsen, {Hans Ole} and Heegaard, {Niels H H} and Hetland, {Merete Lund} and Kristian Stengaard-Pedersen and Peter Junker and Tine Lottenburger and Torkel Ellingsen and {Smedegaard Andersen}, Lis and Ib Hansen and Henrik Skj{\o}dt and Pedersen, {Jens Kristian} and Lauridsen, {Ulrik Birk} and Svendsen, {Anders J} and Ulrik Tarp and Jan P{\o}denphant and Hanne Lindegaard and Aage Vestergaard and Mikkel {\O}stergaard and Kim H{\o}rslev-Petersen",

note = "Keywords: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Disability Evaluation; Double-Blind Method; Female; Humans; Mannose-Binding Lectin; Middle Aged; Peptides, Cyclic; Polymorphism, Genetic; Promoter Regions, Genetic; Questionnaires; Severity of Illness Index; Young Adult",

year = "2009",

month = apr,

day = "1",

doi = "10.3899/jrheum.080846",

language = "English",

volume = "36",

pages = "731--5",

journal = "Journal of Rheumatology",

issn = "0315-162X",

publisher = "Journal of Rheumatology Publishing Co. Ltd.",

number = "4",

}

TY - JOUR

T1 - Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis

AU - Jacobsen, Søren

AU - Garred, Peter

AU - Madsen, Hans Ole

AU - Heegaard, Niels H H

AU - Hetland, Merete Lund

AU - Stengaard-Pedersen, Kristian

AU - Junker, Peter

AU - Lottenburger, Tine

AU - Ellingsen, Torkel

AU - Smedegaard Andersen, Lis

AU - Hansen, Ib

AU - Skjødt, Henrik

AU - Pedersen, Jens Kristian

AU - Lauridsen, Ulrik Birk

AU - Svendsen, Anders J

AU - Tarp, Ulrik

AU - Pødenphant, Jan

AU - Lindegaard, Hanne

AU - Vestergaard, Aage

AU - Østergaard, Mikkel

AU - Hørslev-Petersen, Kim

AU - Jacobsen, Søren

AU - Garred, Peter

AU - Madsen, Hans Ole

AU - Heegaard, Niels H H

AU - Hetland, Merete Lund

AU - Stengaard-Pedersen, Kristian

AU - Junker, Peter

AU - Lottenburger, Tine

AU - Ellingsen, Torkel

AU - Smedegaard Andersen, Lis

AU - Hansen, Ib

AU - Skjødt, Henrik

AU - Pedersen, Jens Kristian

AU - Lauridsen, Ulrik Birk

AU - Svendsen, Anders J

AU - Tarp, Ulrik

AU - Pødenphant, Jan

AU - Lindegaard, Hanne

AU - Vestergaard, Aage

AU - Østergaard, Mikkel

AU - Hørslev-Petersen, Kim

N1 - Keywords: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Disability Evaluation; Double-Blind Method; Female; Humans; Mannose-Binding Lectin; Middle Aged; Peptides, Cyclic; Polymorphism, Genetic; Promoter Regions, Genetic; Questionnaires; Severity of Illness Index; Young Adult

PY - 2009/4/1

Y1 - 2009/4/1

N2 - OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2 high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p=0.02), and physical disability by HAQ (p=0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs. CONCLUSION: The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.

AB - OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2 high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p=0.02), and physical disability by HAQ (p=0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs. CONCLUSION: The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.

U2 - 10.3899/jrheum.080846

DO - 10.3899/jrheum.080846

M3 - Journal article

C2 - 19273450

SN - 0315-162X

VL - 36

SP - 731

EP - 735

JO - Journal of Rheumatology

JF - Journal of Rheumatology

IS - 4

ER -

Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis

Abstract

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