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dc.contributor.authorBesada, Emilio
dc.contributor.authorNossent, Johannes C.
dc.date.accessioned2016-09-21T06:33:53Z
dc.date.available2016-09-21T06:33:53Z
dc.date.issued2016-09-20
dc.description.abstract<b>Introduction</b> <br> Rituximab (RTX) is a B cell-depleting agent approved for the treatment of granulomatosis with polyangiitis (GPA). RTX reduces antibody producing precursor plasma cells and inhibits B and T cells interaction. Infections related to T cell immunodeficiency are not infrequent during RTX treatment. Our study investigated CD4 cell count and CD4/CD8 ratio in GPA patients during the first two years of long-term RTX treatment. <br><b> Methods</b> <br> A single centre cohort study of 35 patients who received median total cumulative dose of cyclophosphamide (CYC) of 15 g and were treated with RTX 2 g followed by retreatment with either 2 g once annually or 1 g biannually. Serum levels of total immunoglobulin (Ig) and lymphocytes subsets were recorded at RTX initiation and at 3, 6, 12, 18 and 24 months. Low CD4 count and inverted CD4/CD8 ratio were defined as CD4 < 0.3 × 10<sup>9</sup>/l and ratio < 1. <br> <b>Results</b> <br> The CD4 cell count and CD4/CD8 ratio decreased slightly following the initial RTX treatment and then increased gradually during maintenance treatment. While the proportion of patients with low CD4 cell count decreased from 43% at baseline to 18% at 24 months, the ratio remained inverted in 40%. Oral daily prednisolone dose at baseline, CYC exposure and the maintenance regimen did not influence the CD4 cell count and ratio. Being older (p = 0.012) and having a higher CRP (p = 0.044) and ESR (p = 0.024) at baseline significantly increased the risk of inverted CD4/CD8 ratio at 24 months. Inverted ratio at baseline associated with lower total Ig levels during the study. <br> <b>Conclusions</b> <br> Overall, the CD4 and CD4/CD8 ratio increased during maintenance RTX therapy in GPA with no discernible impact of other immunosuppressive therapy. However the increase in CD4 was not followed by an increase in the CD4/CD8 ratio, especially in older patients. Inverted CD4/CD8 ratio associated with lower Ig levels, suggesting a more profound B cell depleting effect of RTX with a relative increase in CD8+ lymphocytes.en_US
dc.descriptionPublisher's version, source: <a href=http://doi.org/10.7717/peerj.2487>http://doi.org/10.7717/peerj.2487</a>.en_US
dc.identifier.citationPeerJ (2016) 4:e2487en_US
dc.identifier.cristinIDFRIDAID 1383481
dc.identifier.doi10.7717/peerj.2487
dc.identifier.issn2167-8359
dc.identifier.urihttps://hdl.handle.net/10037/9737
dc.language.isoengen_US
dc.publisherPeerJen_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Reumatologi: 759en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Generell indremedisin: 770en_US
dc.subjectANCA-associated vasculitisen_US
dc.subjectRituximaben_US
dc.subjectGranulomatosis with polyangiitisen_US
dc.subjectCD4/CD8 ratioen_US
dc.subjectCD4 cellen_US
dc.subjectCD8 cellen_US
dc.subjectInfectionen_US
dc.subjectImmunosuppressionen_US
dc.subjectB cell depletionen_US
dc.subjectHypogammaglobulinemiaen_US
dc.titleCD4 cell count and CD4/CD8 ratio increase during rituximab maintenance in Granulomatosis with polyangiitis patientsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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