Anti-carbamylated protein antibody isotype pattern differs between palindromic rheumatism and rheumatoid arthritis

Raul Castellanos-Moreira; Sebastian C Rodriguez-Garcia; Sonia Cabrera-Villalba; María José Gomara; Georgina Salvador; Virginia Ruiz-Esquide; Julio Ramirez; Jose Inciarte-Mundo; Rosa Morla; Cristina Garcia-Moreno; Andrea Cuervo; Jose A Gómez-Puerta; Juan D Cañete; Isabel Haro; Raimon Sanmarti

doi:10.1177/1759720X20978139

Anti-carbamylated protein antibody isotype pattern differs between palindromic rheumatism and rheumatoid arthritis

Ther Adv Musculoskelet Dis. 2020 Dec 10:12:1759720X20978139. doi: 10.1177/1759720X20978139. eCollection 2020.

Authors

Raul Castellanos-Moreira¹, Sebastian C Rodriguez-Garcia¹, Sonia Cabrera-Villalba¹, María José Gomara², Georgina Salvador³, Virginia Ruiz-Esquide¹, Julio Ramirez¹, Jose Inciarte-Mundo¹, Rosa Morla¹, Cristina Garcia-Moreno², Andrea Cuervo¹, Jose A Gómez-Puerta¹, Juan D Cañete¹, Isabel Haro², Raimon Sanmarti⁴

Affiliations

¹ Arthritis Unit, Rheumatology Department, Hospital Clinic of Barcelona, Barcelona, Spain.
² Unit of Synthesis and Biomedical Applications of Peptides, Institute of Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Barcelona, Spain.
³ Rheumatology Department, University Hospital Mutua Tarrasa, Barcelona, Spain.
⁴ Arthritis Unit, Rheumatology Department, Hospital Clinic of Barcelona, Villarroel 170, Barcelona, 08036, Spain.

Abstract

Background: A restricted response against citrullinated peptides/proteins, with less isotype usage, has been found in palindromic rheumatism (PR) in comparison with rheumatoid arthritis (RA). We hypothesized that this different antibody response may be observed for other post-translational modified proteins. We compared the prevalence and isotype usage of two specificities of anti-carbamylated peptide/protein antibodies (Anti-CarP) in patients with PR and RA.

Methods: Cross-sectional study including 54 patients with pure PR and 53 patients with RA, matched by sex, age, disease duration and ACPA. Anti-CarP specificities were determined by home-made enzyme-linked immunosorbent assay tests using a synthetic chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) and fetal calf serum (FCS) homocitrullinated protein as antigens. IgG, IgA and IgM isotypes were measured.

Results: Anti-CarP were positive (CFFHP or FCS) in 24% and 64% of patients with PR and RA, respectively (p < 0.005). All Anti-CarP isotype proportions were significantly lower in PR than in RA: Anti-CarP-IgG (24% versus 51%), Anti-CarP-IgA (7% versus 34%) and Anti-CarP-IgM (7% versus 36%). Mean titers of Anti-CarP isotypes were also lower in PR. In Anti-CarP positive patients, the isotype distribution differed between PR and RA: IgG Anti-CarP was used in all PR patients and in 79% of RA patients. By contrast, a significantly lower isotype usage of both IgA (31% versus 53%) and IgM (31% versus 56%) was observed in PR patients. No significant differences in clinical or demographic characteristics were observed according to Anti-CarP status in PR patients, except for a higher prevalence of ACPA and higher mean titers of ACPA and rheumatoid factor in Anti-CarP positive patients.

Conclusion: Anti-CarP are found in patients with PR but in a lower proportion and with a different isotype usage from in RA, suggesting a distinct B cell response to homocitrullinated antigens in PR.

Keywords: ACPA; Anti-CarP; B cells; autoantibodies; palindromic rheumatism; rheumatoid arthritis.