NK cell markers predict the efficacy of IV immunoglobulins in CIDP

Mausberg, Anne K.; Heininger, Maximilian K.; Hörste, Gerd Meyer zu; Cordes, Steffen; Fleischer, Michael; Szepanowski, Fabian; Kleinschnitz, Christoph; Hartung, Hans‐Peter; Kieseier, Bernd C.; Stettner, Mark

doi:10.1212/nxi.0000000000000884

Cited by 9 publications

(11 citation statements)

References 34 publications

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“…Ahmadi et al demonstrated that a low dose of IVIG upregulated inhibitory receptors and decreased activating receptors, which coincided with a decrease in natural cytotoxicity by PBMCs from women with recurrent spontaneous abortion (10). Additionally, Mausberg et al found that multiple NK receptors, including CD94, were downregulated at the transcriptional level in PBMCs post IVIG infusion of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) (33). After a high dose of IVIG, we did not observe similar changes in the receptors but did find a marked decrease in both the expression of the granule exocytosis marker, CD107a, and in cytotoxicity that was most striking in the clinically homogenous KD group.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, Mausberg et al. found that multiple NK receptors, including CD94, were downregulated at the transcriptional level in PBMCs post IVIG infusion of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) ( 33 ). After a high dose of IVIG, we did not observe similar changes in the receptors but did find a marked decrease in both the expression of the granule exocytosis marker, CD107a, and in cytotoxicity that was most striking in the clinically homogenous KD group.…”

Section: Discussionmentioning

confidence: 99%

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High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

et al. 2021

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Intravenous immunoglobulin (IVIG) is an effective immunomodulatory treatment for immune dysregulation diseases. However, the mechanisms by which it reduces systemic inflammation are not well understood. NK cell cytotoxicity is decreased by IVIG in women with reduced fertility, but IVIG effects on NK cells in immune dysregulation are less clear. We hypothesized that IVIG modulation of lymphocyte function, especially in NK cells, is important for resolution of inflammation. Our aim was to identify IVIG-induced changes in a cohort of patients with Kawasaki disease (KD) and those that occur broadly in pediatric patients with various immune dysregulatory diseases. Peripheral blood mononuclear cells (PBMCs) of patients with KD or autoimmune/inflammatory diseases were phenotyped pre and post high dose IVIG treatment by flow cytometry. In KD patients, after IVIG infusion Treg cell frequency and the proportion of activated CD25+ immunoregulatory CD56bright NK cells was increased, and multiple lymphocyte subsets showed increased expression of the lymphoid tissue homing receptor CD62L. Importantly, IVIG treatment decreased the frequency of cells expressing the degranulation marker CD107a among cytotoxic CD56dim NK cells, which was reflected in a significant reduction in target cell killing and in decreased production of multiple pro-inflammatory mediators. Interestingly, the activating receptor CD336 was expressed on a higher proportion of CD56bright NK cells after IVIG in both KD and autoimmune/inflammatory patients while other NK receptors were increased differentially in each cohort. In autoimmune/inflammatory patients IVIG induced the proliferation marker CD71 on a higher percentage of CD56dim NK cells, and in contrast to KD patients, CD107a+ cells were increased in this subset. Furthermore, when PBMCs were stimulated ex vivo with IL-2 or Candida antigen in autologous plasma, more of the CD4+ T cells of KD patients expressed CD25 after IVIG therapy but fewer cytotoxic T cells were degranulated based on CD107a expression. In summary, IVIG treatment in patients with immune dysregulation has multiple effects, especially on NK cell subsets and CD4+ T cells, which are compatible with promoting resolution of inflammation. These novel findings provide insight into the immunomodulatory actions of IVIG in autoimmune and inflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

et al. 2021

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“…One explanation could be that a subgroup of patients with sustained immunological remission confounded the results due to a subjective IVIg response and continued to receive IVIg, which is in line with a recent study which demonstrated that the placebo effect is a common challenge after long‐term immunoglobulin treatment in CIDP [27]. Furthermore, the reduction of NK dim cell frequencies after IVIg administration, also a marker for IVIg response [19], was not significantly different to that in SCIg recipients. Likewise, myeloid dendritic cells were not differentially altered by IVIg and SCIg in CIDP.…”

Section: Discussionmentioning

confidence: 70%

“…This latter effect is important in CIDP since impaired B-cell maturation and reduced CD32b expression on B cells and monocytes are IVIg-responsive features [17]. Furthermore, IVIg treatment reduces myeloid dendritic cells and cytotoxic natural killer cells (NK dim ) that are also involved in the pathogenesis of CIDP [18,19].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of intravenous and subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: An observational study

Svačina,

Meißner,

Schweitzer

et al. 2023

Euro J of Neurology

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Background and purposeIt is not known whether the route of administration affects the mechanisms of action of therapeutic immunoglobulin in chronic inflammatory demyelinating polyneuropathy (CIDP). The aim of this study, therefore, was to compare the immunomodulatory effects of intravenous (IVIg) and subcutaneous immunoglobulin (SCIg) in patients with CIDP and in IVIg‐treated common variable immunodeficiency (CVID) patients.MethodsSerum and peripheral blood mononuclear cell samples were obtained from 30 CIDP patients receiving IVIg, 10 CIDP patients receiving SCIg, and 15 patients with CVID receiving IVIg. Samples and clinical data were obtained prior to IVIg/SCIg and at 3 days, 7 days, and, in CIDP patients receiving IVIg, 21 days post‐administration. Serum cytokines were assessed by Luminex‐based multiplex assay and enzyme‐linked immunosorbent assay. Immune cells were characterized by flow cytometry.ResultsImmune cell profiles of CIDP and CVID patients differed in frequencies of myeloid dendritic cells and cytotoxic natural killer cells. During treatment with IVIg or SCIg in CIDP patients, cellular immunomarkers were largely similar. CIDP patients receiving IVIg had higher macrophage inflammatory protein (MIP)‐1α (p = 0.01), interleukin (IL)‐4 (p = 0.04), and IL‐33 (p = 0.04) levels than SCIg recipients. IVIg treatment more broadly modulated cytokines in CIDP than SCIg treatment.ConclusionsOur study demonstrates that the modulation of cellular immunomarkers in CIDP is independent of the application route of therapeutic immunoglobulin. Minor differences were observed between CIDP and CVID patients. In contrast, cytokines were differentially modulated by IVIg and SCIg in CIDP.

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“…Then, by preliminary screening of innate immune cells (mast cells, macrophages, MDSCs, neutrophils, and natural killer cells) and adaptive immune cells (B cells and CD8 + T cells) in the cholangiocarcinoma, we observed that NNMT was specifically associated with the gene signature of macrophages and MDSC (Figures S2B, C http://links.lww.com/HEP/A36). [14][15][16][17][18] Therefore, this study further detected the infiltration of these 2 cells in GBC.…”

Section: Nnmt Is Overexpressed In Human Gbc and Is Associated With Im...mentioning

confidence: 85%

Nicotinamide N-methyltransferase promotes M2 macrophage polarization by IL6 and MDSC conversion by GM-CSF in gallbladder carcinoma

Yang

Miao

et al. 2023

Hepatology

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Background and Aims: Nicotinamide N-methyltransferase (NNMT), an enzyme responsible for the methylation of nicotinamide, is involved in many metabolic pathways in adipose tissue and the liver. However, the role of NNMT in editing the tumor immune microenvironment is not well understood. Approach and Results: Here, we identified that NNMT can promote IL6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by decreasing the tri-methyl-histone H3 levels on the promoters of IL6 and CSF2 (encoding GM-CSF) and CCAAT/Enhancer Binding Protein, an essential transcription factor for IL6 expression, thus promoting differentiation of macrophages into M2 type tumor-associated macrophages and generation of myeloid-derived suppressor cells from peripheral blood mononuclear cells. Treatment of xenografted tumor models overexpressing NNMT gallbladder carcinoma (GBC) cells with the NNMT inhibitor JBSNF-000088 resulted in compromised tumor development and decreased expression levels of IL6, GM-CSF, tumorassociated macrophage marker CD206, and myeloid-derived suppressor cell marker CD33 but increased expression levels of CD8. In addition, elevated expression of NNMT in tumors of patients with GBC was correlated with increased expression levels of CD206 and CD33 but with decreased levels of CD8 and survival of patients.

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NK cell markers predict the efficacy of IV immunoglobulins in CIDP

Cited by 9 publications

References 34 publications

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

Immunomodulatory effects of intravenous and subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: An observational study

Nicotinamide N-methyltransferase promotes M2 macrophage polarization by IL6 and MDSC conversion by GM-CSF in gallbladder carcinoma

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