Increased antibody production in peripheral blood mononuclear cells after plasma exchange therapy in multiple sclerosis

Dau, Peter C.

doi:10.1016/0165-5728(95)00121-4

Cited by 27 publications

(22 citation statements)

References 15 publications

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“…However, patients with a chronic autoimmune disease, treated with plasmapheresis either as a result of acute exacerbation or as a long-term therapeutic strategy, will, nevertheless, profit in most cases from the long-term effects of immunosuppressants. The absence of an increase of B-cell activity after IA contradicts a previous study 7 but, nevertheless, excludes the possibility that IA therapy itself might promote antibody synthesis by release of antigenic peptides. On the contrary, as indicated in the patient with active Guillain-Barré syndrome, characterized serologically by highly activated B cells and increased light chains, removal of autoantibodies and immune complexes might lead to a normalization of both B-cell activity markers and flc levels.…”

Section: Resultscontrasting

confidence: 44%

“…A large number of studies have provided evidence for enhanced antibody synthesis after immunoglobulin depletion and thus for the existence of an immunoregulatory feedback mechanism. [1][2][3][4][5][6][7] In contrast, Charlton and colleagues [8][9][10] demonstrated with a series of animal experiments that the rapid increase of antibody serum levels after plasmapheresis could be explained by immunoglobulin backflow from extravascular space and decreased catabolism alone. More than 10 years later the lack of an increased antibody synthesis in a low immunoglobulin state was confirmed in the excellent studies by Junghans and Anderson 11 and by Junghans.…”

Section: Introductionmentioning

confidence: 99%

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Influence of plasma immunoglobulin level on antibody synthesis

Goldammer

Derfler

Herkner

et al. 2002

Blood

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In previous experimental animal studies it has been demonstrated that antibody depletion is not followed by increased antibody synthesis. To assess whether these results are conferrable to antibody-depleted humans, we measured free light chains (flcs) as markers of current antibody synthesis in 8 patients treated with immunoadsorption (IA) therapy. Specific and bulk immunoglobulin levels were obtained simultaneously. The mean serum flc concentration increased to the preapheresis value within 1 day and remained unchanged thereafter. Total immunoglobulin G (IgG) and specific antibody concentrations increased to pretreatment values in 88% and 43% of the patients, respectively, and remained below the original values in the others. In conclusion, the lack of increased flc synthesis after IA confirms the absence of a feedback mechanism regulating antibody synthesis. IntroductionThe regulation of serum antibody levels has been a subject of debate for several decades. A large number of studies have provided evidence for enhanced antibody synthesis after immunoglobulin depletion and thus for the existence of an immunoregulatory feedback mechanism. [1][2][3][4][5][6][7] In contrast, Charlton and colleagues 8-10 demonstrated with a series of animal experiments that the rapid increase of antibody serum levels after plasmapheresis could be explained by immunoglobulin backflow from extravascular space and decreased catabolism alone. More than 10 years later the lack of an increased antibody synthesis in a low immunoglobulin state was confirmed in the excellent studies by Junghans and Anderson 11 and by Junghans. 12 Knock-out mice with disrupted immunoglobulin G (IgG) protection receptors, which effect increased catabolism of IgG and subsequently low IgG serum levels, had a similar biosynthesis rate as normal control subjects.The complex metabolism of IgG has so far prevented exact measurement of immunoglobulin synthesis in humans with low antibody levels. However, a prerequisite for immunoglobulin assembly is the synthesis of free light chains (flcs) that are produced in excess during antibody production and secreted as free or monomers into the vascular space. 13,14 Because flcs have a half-live of only 2 to 4 hours, 15 they reflect current immunoglobulin production and can be used for estimating the activity of diseases accompanied by autoantibody synthesis. 16,17 We hypothesized that increased antibody synthesis after immunoglobulin depletion would be accompanied by increased flc serum levels and measured free and light chain concentrations in 8 patients undergoing immunoadsorption (IA) therapy. Study designThe study protocol was approved by the local ethics committee, and the patients' informed consent was obtained. Eight patients with various autoimmune diseases and normal kidney function treated with IA therapy were recruited (Table 1). Concomitant immunosuppressive therapy was prednisolone (n ϭ 4), mycophenolate mofetil (n ϭ 3), and cyclosporine A (n ϭ 1); 3 patients received no additional therapy. We recruited additi...

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Section: Resultscontrasting

confidence: 44%

Section: Introductionmentioning

confidence: 99%

Influence of plasma immunoglobulin level on antibody synthesis

Goldammer

Derfler

Herkner

et al. 2002

Blood

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“…The phenomenon of antibody rebound after TPE is well described. Dau reported a significant increase in B‐cell percentage in peripheral blood lymphocyte populations with TPE, which leads to increasing antibody production. We hypothesize that at least four other mechanisms may account for rebound in the setting of TPE for AMR, as follows: 1) Naïve cells may be activated by TPE.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of plasmapheresis on donor‐specific antibody reduction by HLA specificity in post–kidney transplant recipients

et al. 2014

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BACKGROUND Donor-specific antibodies (DSAs) to HLA antigens can cause acute antibody-mediated rejection (AMR) after kidney transplantation (Txp). Therapeutic plasma exchange (TPE) has been used for AMR treatment; however, DSA reduction rates are inconsistent. We investigated DSA reduction rates by HLA specificity and clinical outcome. STUDY DESIGN AND METHODS Sixty-four courses of TPE for 56 kidney Txp recipients with high DSA were investigated. Dates of TPE procedures and Txp, patients’ age, sex, race, creatinine (Cr), and mean fluorescent intensity (MFI) of DSA were retrieved. MFI reduction rate after one to three TPE and four to six TPE procedures were calculated by HLA DSA specificity in each patient, and the mean reduction rates were compared. The relationship of TPE treatment, MFI or Cr improvement rate, and graft age was also investigated. RESULTS Patients received a mean 6.0 TPE procedures. Most received intravenous immunoglobulin after TPE and immunosuppressives. Forty-two cases (65.6%) had DSA to HLA Class I and 54 cases (84.4%) to Class II, including 32 cases (50.0%) to both. Mean MFI reduction rates after one to three TPE and four to six TPE procedures were 25.7 and 37.1% in HLA Class I, 25.1 and 34.2% in Class II, and 14.3 and 19.9% in DR51-53. The mean Cr improvements at the end of TPE and 3 and 6 months after TPE were 3.41, −0.37, and −0.72%, respectively. CONCLUSION Six TPE procedures decreased DSA more than three TPE procedures, but reduction rate was lower by the second three TPE procedures than the first three TPE procedures. Although the mean Cr improvement was minimal, the treatment has good potential to stop further deterioration of kidney function. Better Cr improvement rate is correlated with the graft age.

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“…This study suggested that PE in the absence of other immunosuppressive drugs may have a role in the treatment of severe episodes of MS. In an another study (5) of intensive PE in 10 MS patients without immunosuppression, functional and neurological improvement occurred in 9 patients. This study also demonstrated very elegantly that PE brings about an activation of the immune system and suggested the possible need for adjunctive immunosuppression to control antibody production in autoimmune diseases with subacute relapsing or chronic disease when PE is employed as a therapeutic modality.…”

Section: Plasma Exchange In Acute Msmentioning

confidence: 99%

Therapeutic Apheresis in Multiple Sclerosis and Other Central Nervous System Disorders

Khatri¹

2000

Therapeutic Apheresis

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Although the cause of multiple sclerosis (MS) remains unknown, the recent advances in research and the use of immunomodulating therapies have revolutionalized the way this disease is now approached. Apheresis is but one of the various immunomodulating therapies successfully used in MS. Pilot and double‐blind randomized controlled studies, long‐term follow‐up studies, and the possible mechanism of action of therapeutic apheresis in MS are discussed. Based on our current knowledge, as well as on the available published data, it is concluded that apheresis is an effective therapy in severely progressive MS (both acute and chronic) when conventional therapies have failed.

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Increased antibody production in peripheral blood mononuclear cells after plasma exchange therapy in multiple sclerosis

Cited by 27 publications

References 15 publications

Influence of plasma immunoglobulin level on antibody synthesis

Influence of plasma immunoglobulin level on antibody synthesis

Efficacy of plasmapheresis on donor‐specific antibody reduction by HLA specificity in post–kidney transplant recipients

Therapeutic Apheresis in Multiple Sclerosis and Other Central Nervous System Disorders

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