Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control

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To evaluate long-term effects on gamma-globulins and autoantibodies of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients.


Eighteen RA patients undergoing abatacept (ABA-RA) and 18 age/sex-matched patients treated with TNFi (TNFi-RA) were compared regarding clinical data, total gamma-globulins (TGG), specific subtypes (IgG, IgM, IgA), free light chains (FLC), IgM/IgG rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP3), and anti-mutated citrullinated vimentin (anti-MCV), assessed before and every 6 months, up to 24 months. Exclusion criteria: previous abatacept/rituximab or low TGG (< 0.7 g/dL).


At baseline, female sex (78 vs. 78%), age (55 vs. 53 years), DAS28 (5.73 vs. 5.67), TGG (1.4 vs. 1.35 g/dL), IgG (1168 vs. 1079 mg/dL), IgM (107 vs. 113 mg/dL), IgA (333 vs. 322 mg/dL), kappa (342 vs. 249 mg/dL), lambda (170 vs. 150 mg/dL), IgM-RF (76 vs. 53 UI), IgG-RF (63 vs. 25 UI), anti-CCP3 (216 vs. 189 UI), and anti-MCV (202 vs. 102 UI) were comparable in ABA-RA and TNFi-RA (p > 0.05). Similar disease activity improvement was observed in both groups. In ABA-RA, significant decreases (p < 0.05) were observed in TGG (1.4 vs. 1.05 g/dL), IgG (1168 vs. 997), IgA (333 vs. 278 mg/dL), kappa (342 vs. 257 mg/dL), lambda (170 vs. 144 mg/dL), IgM-RF (76 vs. 37 UI), IgG-RF (65 vs. 24 UI), anti-CCP3 (216 vs. 183 UI), and anti-MCV (202 vs. 60 UI) at 6 months, without further decreases. In contrast, TNFi-RA showed no decrease in any of such parameters. ABA-RA also had more often transient IgG levels under the lower limit of normality (66.7% vs. 33.3%, p = 0.046). No severe infection occurred. DAS28, ESR, and CRP correlated significantly to gamma-globulins and FLC at baseline (p < 0.05), but these correlations were longitudinally lost in ABA-RA, but not in TNFi-RA.


ABA, but not TNFi, induces a safe, persistent, long-term, and non-progressive reduction in gamma-globulins and autoantibodies, including anti-MCV. This pattern is dissociated from disease activity control.

Key Points
ABA induces a long-term and non-progressive reduction in gamma-globulins and FLC, which occurs regardless of disease activity control.
ABA-induced reduction in gamma-globulins and FLC promotes a dissociation of such parameters and disease activity.
The same pattern of reduction is observed in autoantibodies: IgM-RF, IgG-RF, anti-CCP3, and anti-MCV.
Low transient IgG can be observed in RA patients treated with ABA, but does not correlate to infection.

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Correspondence to Ana C. Medeiros-Ribeiro.

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Ethical standards

The procedures were in accordance with the 1964 Declaration of Helsinki and its later amendments and were approved by the local ethical committee on human experimentation (Comissão de Ética para Análise de Projetos de Pesquisa do HCFMUSP – CAPPesq, project no. 2009/51897-5). An informed consent was obtained from all participants prior to their inclusion in the study.

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Dinis, V.G., Viana, V.T., Leon, E.P. et al. Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control. Clin Rheumatol (2020).

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  • Anti-mutated citrullinated vimentin and anti-cyclic citrullinated peptide
  • Biological therapies
  • Infections and arthritis
  • Rheumatoid arthritis
  • Rheumatoid factor