Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus

Eickenberg, Sebastian; Mickholz, E.; Jung, Elisabeth; Nofer, Jerzy–Roch; Pavenstädt, Hermann; Jacobi, Annett M.

doi:10.1186/ar3835

Cited by 68 publications

(67 citation statements)

References 42 publications

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“…Mycophenolate mofetil selectively inhibits the growth of T and B cells and does not affect other immune cells because other cells are able to recover purines via a separate salvage pathway. 26 In addition, Eickenberg et al 27 investigated patients with systemic lupus erythematosus and reported that transitional and naive B-cell counts were significantly higher in patients who were taking MMF compared with those who were taking AZA, but markedly lower frequencies of plasmablasts were detected in patients who were mitoxantrone 16 efficacy studies, our MMF-treated patients had similar ARR after treatment and relapse-free rates but tended to have lower ARR and EDSS scores before treatment than in other immunosuppressant studies (Table 3). Our study comprised only 7 patients (12%) with severe neurological impairments (EDSS score >6), whereas the studies that used mitoxantrone 16 and rituximab 11 consisted of 26% to 45% of those cases.…”

Section: Discussionmentioning

confidence: 98%

Mycophenolate Mofetil in the Treatment of Neuromyelitis Optica Spectrum Disorder

et al. 2014

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IMPORTANCE Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disorder of the central nervous system. Recently, various immunosuppressant medications were introduced as therapeutic options for preventing relapse of NMOSD. However, our understanding of the effectiveness of mycophenolate mofetil (MMF) in treating patients with NMOSD is based on only a small number of studies.OBJECTIVE To evaluate the efficacy and safety of MMF treatment in patients with NMOSD. DESIGN, SETTING, AND PARTICIPANTSA 3-center retrospective review of our experiences, examining results from 59 patients with NMOSD (24 with neuromyelitis optica and 35 with a limited form of the disease) who were treated with MMF (1000-2000 mg/d). MAIN OUTCOMES AND MEASURESPatients' annualized relapse rate, disability as measured by the Expanded Disability Status Scale, and experience of adverse effects due to MMF were assessed. RESULTSOf the 59 patients, 1 with NMOSD who had to discontinue MMF use in the first month due to a rash was excluded. The remaining 58 patients were included in the drug-efficacy analysis. The median post-MMF annualized relapse rate was significantly lower than the pre-MMF annualized relapse rate (0.0 vs 1.5; P < .001). The Expanded Disability Status Scale scores also significantly decreased after MMF treatment (3.0 vs 2.5; P = .005). Thirty-five patients (60%) were relapse free, and Expanded Disability Status Scale scores were stabilized or improved in 53 patients (91%). Fourteen patients discontinued MMF treatment owing to ongoing relapse (10 patients), rash (1 patient), pregnancy (1 patient), and financial problems (2 patients), but MMF was generally well tolerated. CONCLUSIONS AND RELEVANCEIn this observational study, MMF treatment induced reduction of relapse frequency, stabilized or improved disability, and was well tolerated in patients with NMOSD.

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Section: Discussionmentioning

confidence: 98%

Mycophenolate Mofetil in the Treatment of Neuromyelitis Optica Spectrum Disorder

et al. 2014

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“…In SLE, MMF, but not AZT or hydroxychloroquine, treatment has been associated with reduced frequency of switched memory B cells and modest decreases in levels of serum Ig and of anti‐dsDNA antibodies 40, 41, 42. The composition of B cell subpopulations may vary between individuals with SLE and after rituximab; repopulation appears to recapitulate ontogeny, perhaps further influenced by antigen stimulation 43.…”

Section: Discussionmentioning

confidence: 99%

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Reddy

Martinez

Isenberg

et al. 2017

Arthritis Care & Research

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ObjectiveB cell–depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with systemic lupus erythematosus (SLE). The aim of this observational study was to document long‐term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice.MethodsWe included 57 consecutive patients with SLE treated with rituximab and concomitant/sequential immunosuppressants and measured serum total IgG, IgM, and IgA and IgG anti‐dsDNA antibodies, over a median of 48 months most recent followup. Flow cytometry was used prospectively to assess B cell phenotypes in 17 of 57 patients.ResultsTwelve patients (21%) had persistent IgM hypogammaglobulinemia (<0.4 gm/liter), and 4 of 57 (5%) had low IgG (<7 gm/liter) at the most recent followup (range 12–144 months). This was not associated with serious adverse events or high anti–double‐stranded DNA (anti‐dsDNA) antibodies (>1,000 IU/ml; normal <50 IU/ml). Factors predictive of low serum IgM included baseline serum IgM ≤0.8 gm/liter (receiver operator curve analysis) and subsequent therapy with mycophenolate mofetil (MMF; odds ratio 6.8, compared with other immunosuppressants). In patients maintaining normal IgM levels (9 of 17), the frequency of circulating IgD+CD27+ B cells was significantly higher (P = 0.05). At 12 months after rituximab, 7 of 30 SLE patients with baseline anti‐dsDNA ≤1,000 IU/ml had lost seropositivity.ConclusionLower baseline serum IgM levels and sequential therapy with MMF were predictive of IgM hypogammaglobulinemia after rituximab in SLE, but this was not associated with higher levels of anti‐dsDNA antibodies or an increased risk of infections. This provides useful directions for clinicians regarding rituximab and sequential immunosuppressive treatment for patients with SLE.

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“…Considering these properties, it is not surprising that significant hypogammaglobulinaemia associated with bronchiectasis has been reported in seven of 23 patients with recurrent chest infections postrenal transplantation [81]. MMF-induced hypogammaglobulinaemia has also been observed in patients with systemic lupus erythematosus though it is unclear whether this was accompanied by a significant burden of infections [82]. In contrast to MMF, azathioprine a related purine inhibitor has minimal propensity to induce hypogammaglobulinaemia [83].…”

Section: Mycophenolate Mofetilmentioning

confidence: 97%

Secondary antibody deficiencies

Dhalla

Misbah²

2015

Current Opinion in Allergy &Amp; Clinical Immunology

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Causes of secondary antibody deficiency include B-cell lymphoproliferative disease, notably chronic lymphocytic leukaemia and multiple myeloma, protein losing states, disorders of lymphatic circulation, increased immunoglobulin catabolism and a growing number of therapeutic agents. At-risk patients should be closely monitored for the development of hypogammaglobulinaemia, B-cell function should be defined where appropriate with specific antibody responses to immunization antigens and where there is a significant burden of infections patients should be treated with prophylactic antibiotics and/or replacement immunoglobulin.

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Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus

Cited by 68 publications

References 42 publications

Mycophenolate Mofetil in the Treatment of Neuromyelitis Optica Spectrum Disorder

Mycophenolate Mofetil in the Treatment of Neuromyelitis Optica Spectrum Disorder

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Secondary antibody deficiencies

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