Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis Patients with Lymphoma.

Baecklund10,  Eva, Smedby3,  Karin Ekström, Backlin5,  Carin, Ronnelid2,  Johan, Ahlin2,  Erik, Toes6,  Rene, Askling4,  Johan

Cancer Center, Massachusetts General Hospital, Boston
Rheumatology, Medical Sciences, Uppsala University, Uppsala, Sweden
UMass Memorial Medical Center, Worcester, MA
Clinical Immunology, Uppsala University
Epidemiology Unit, Karolinska Institutet at Karolinska University Hospital, Stockholm
Epidemiology, Rheumatology, Karolinska Institutet at Karolinska University Hospital, Stockholm
Genetics and Pathology, Uppsala University
Immunology, Leiden University Medical Center
Immunology, Massachusetts General Hospital, Boston
Karolinska University Hospital, Stockholm, Sweden
Rheumatology, Leiden University Medical Center

Background:

The risk for lymphoma and, in particular, diffuse large B-cell lymphoma (DLBCL), is increased in patients with rheumatoid arthritis (RA). No biomarkers for the development of lymphoma in patients with RA have been identified.

Objective:

To investigate if anti-CCP antibody levels and subclasses are associated with occurrence of lymphoma in patients with RA.

Methods:

We identified 37 index patients with RA and subsequent lymphoma from two population-based Swedish case-control studies, one of lymphoma (the SCALE study, 1999–2002) and the other of RA (the EIRA study, 1996–2006). To each index RA-lymphoma case, three pairs of control subjects were matched based upon age at diagnosis of RA or lymphoma (± 5 years) and lymphoma subtype. Controls consisted of 73 patients with RA (EIRA), 73 patients with lymphoma only (SCALE), and 74 individuals with neither disorder (EIRA). Blood samples were collected from all subjects at either diagnosis of lymphoma (SCALE) or of RA (EIRA). The self-reported RA diagnosis (SCALE) was validated in medical records. Blood samples from all 257 study subjects were analyzed for anti-CCP IgG (ELISA, Eurodiagnostica) and ACPA-isotypes: anti-CCP IgG1–4, IgA, and IgM (Leiden). Anti-CCP IgG levels >=25 U/ml were defined as positive. The chi2 and Wilcoxon rank sum tests were used for statistical analysis.

Results:

Similar proportions of patients with RA only (65%) and of patients with RA-lymphoma (65%) had positive anti-CCP IgG levels, as did lymphoma cases (1.4%) and population controls (3%). Similar results were obtained for all anti-CCP subclasses. The median level of anti-CCP IgG in index patients with RA- lymphoma (306 U/ml; min 1- max 5033) was higher than in non-lymphoma RA patients (140 U/ml; min 0-max 5706), but the difference was not statistically significant (p=0.25).

The most common lymphoma subtype among the index cases was DLBCL (37%). The median anti-CCP IgG was numerically higher in RA patients with DLBCL (495 U/ml; min 1-max 5033) compared to patients with RA and other non-Hodgkin lymphoma subtypes (175 U/ml; min 1-max 3626), (p=0.87).

Conclusion:

This population-based study with carefully matched controls does not support an association between IgG anti-CCP antibody positivity or levels or ACPA subclasses (IgG, IgG1–4, M or A) and lymphoma occurrence in RA. Further studies are needed to identify other potential biomarkers of lymphoma occurrence in RA.

To cite this abstract, please use the following information:
Baecklund, Eva, Smedby, Karin Ekström, Backlin, Carin, Ronnelid, Johan, Ahlin, Erik, Toes, Rene, et al; Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis Patients with Lymphoma. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1015
DOI: 10.1002/art.28782

Abstract Supplement

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