Interaction between B-cell activation factor and methotrexate impacts immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis

Park, Jin Kyun; Lee, Ye Ji; Bitoun, Samuel; Winthrop, Kevin; Choi, Yunhee; Lee, Eun Bong; Mariette, Xavier

doi:10.1136/annrheumdis-2018-214025

Cited by 20 publications

(16 citation statements)

References 6 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, anti-CD47 antibody could have paradoxical effects in SLE patients; anti-CD47 antibody might promote pro-inflammatory response whereas it can enhance the treatment response to B cell depletion with anti-CD20 antibodies. A similar effect of B-cell activating factor (BAFF) was observed in rheumatoid arthritis; BAFF activates B cells and increases disease activity, but it can negatively impact humoral response in combination with methotrexate via increasing extra-cellular anti-inflammatory adenosine concentration [ 31 ]. The potential therapeutic role of anti-CD47 antibody in SLE treatment needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus

Park

Lee

Park

et al. 2021

Cells

Self Cite

View full text Add to dashboard Cite

Background: To investigate the role of CD47 in inflammatory responses in systemic lupus erythematosus (SLE). Methods: Expression of CD47 and signal regulatory protein alpha (SIRPα) by peripheral blood mononuclear cells (PBMCs) and changes in CD47 expression after exposure to SLE serum, healthy control (HC) serum, recombinant interferon (IFN)-α, or tumor necrosis factor (TNF)-α were examined. Human monocytes and THP1 cells were incubated with lipopolysaccharide (LPS), an anti-CD47 antibody, or both. TNF-α production was examined. Sera from SLE patients and HCs were screened to detect autoantibodies specific for CD47. Results: Twenty-five SLE patients and sixteen HCs were enrolled. CD47 expression by monocytes from SLE patients was higher than those from HCs (mean fluorescence intensity ± SD: 815.9 ± 269.4 vs. 511.5 ± 199.4, respectively; p < 0.001). CD47 expression by monocytes correlated with SLE disease activity (Spearman’s rho = 0.467, p = 0.019). IFN-α but not TNF-α, increased CD47 expression. Exposing monocytes to an anti-CD47 antibody plus LPS increased TNF-α production by 21.0 ± 10.9-fold (compared with 7.3 ± 5.5-fold for LPS alone). Finally, levels of autoantibodies against CD47 were higher in SLE patients than in HCs (21.4 ± 7.1 ng/mL vs. 16.1 ± 3.1 ng/mL, respectively; p = 0.02). Anti-CD47 antibody levels did not correlate with disease activity (Spearman’s rho = −0.11, p = 0.759) or CD47 expression on CD14 monocytes (Spearman’s rho = 0.079, p = 0.838) in patients. Conclusions: CD47 expression by monocytes is upregulated in SLE and correlates with disease activity. CD47 contributes to augmented inflammatory responses in SLE. Targeting CD47 might be a novel treatment for SLE.

show abstract

Section: Discussionmentioning

confidence: 99%

CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus

Park

Lee

Park

et al. 2021

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…The results of clinical studies evaluating the sole effect of MTX on influenza vaccine immunogenicity are somewhat conflicting. Although overall antibody titers were lower, most patients vaccinated while using MTX generally achieved titers sufficient to protect against influenza infection [38,39,[42][43][44][45][46]. Although some studies recommend skipping MTX doses 2 weeks before and 2 weeks after the influenza vaccine in RA patients, some experts do not accept this recommendation because of the risk of RA exacerbation [47].…”

Section: Vaccines and Treatment With Nonbiological Dmardsmentioning

confidence: 99%

A practical approach for vaccinations including COVID-19 in autoimmune/autoinflammatory rheumatic diseases: a non-systematic review

et al. 2021

View full text Add to dashboard Cite

The COVID-19 pandemic has occupied the world agenda since December 2019. With no effective treatment yet, vaccination seems to be the most effective method of prevention. Recently developed vaccines have been approved for emergency use only and are currently applied to large populations. Considering both the underlying pathogenic mechanisms of autoimmune/ autoinflammatory rheumatological diseases (AIIRDs) and the immunosuppressive drugs used in treatment, vaccination for COVID-19 deserves special attention in such patients. In this article, we aimed to give simple messages to the clinicians for COVID-19 vaccination in patients with AIIRDs based upon the current evidence regarding the use of other vaccines in this patient group. For this purpose, we conducted a "Pubmed search" using the following keywords: Influenza, Hepatitis B, Pneumococcal, and Shingles vaccines and the frequently used conventional and biologic disease-modifying antirheumatic drugs (DMARDs). Likewise, an additional search was performed for the COVID-19 immunization in patients with AIIRDs and considering such drugs. In summary, patients with AIIRDs should also be vaccinated against COVID-19, preferably when disease activity is under control and when there is no concurrent infection. Low-degree immunosuppression does not appear to decrease antibody responses to vaccines. Ideally, vaccinations should be done before the initiation of any biological DMARDs. Patients receiving rituximab should be vaccinated at least 4 weeks before or 6 months after treatment. Since tofacitinib may also reduce antibody responses, especially in combination with methotrexate, it may be appropriate to discontinue this drug before vaccination and to restart after 14 days of immunization.

show abstract

“…However, such scenario with a complex pathophysiological constellation does not allow us to rule out the possible impact of the methotrexate therapy, as well as the influence of patient's genetic makeup on the course and outcome of the disease. It is also noteworthy that patient gained appropriate antiviral immunoglobulin levels despite prolonged methotrexate treatment, since it is known that methotrexate can suppress the production of antibodies to neoantigens 55‐57 . As vitamin D3 has been found to promote T helper type 2 (Th2) response, IL‐4 production and Tregs generation, 15,58 such humoral outcome could also be supported by sufficient 25‐OH‐vitamin D3 status in described patient.…”

Section: Discussionmentioning

confidence: 78%