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

BACKGROUND AND PURPOSE: It 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. METHODS: Serum 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. RESULTS: Immune 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. CONCLUSIONS: Our 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.

Antibody response after COVID-19 vaccination in intravenous immunoglobulin-treated immune neuropathies.

BACKGROUND AND PURPOSE: This study assessed the prevalence of anti-SARS-CoV-2 antibodies in therapeutic immunoglobulin and their impact on serological response to COVID-19 mRNA vaccine in patients with intravenous immunoglobulin (IVIg)-treated chronic immune neuropathies. METHODS: Forty-six samples of different brands or lots of IVIg or subcutaneous IgG were analyzed for anti-SARS-CoV-2 IgG using enzyme-linked immunosorbent assay and chemiluminescent microparticle immunoassay. Blood sera from 16 patients with immune neuropathies were prospectively analyzed for anti-SARS-CoV-2 IgA, IgG, and IgM before and 1 week after IVIg infusion subsequent to consecutive COVID-19 mRNA vaccine doses and after 12 weeks. These were compared to 42 healthy subjects. RESULTS: Twenty-four (52%) therapeutic immunoglobulin samples contained anti-SARS-CoV-2 IgG. All patients with immune neuropathies (mean age = 65 ± 16 years, 25% female) were positive for anti-SARS-CoV-2 IgG after COVID-19 vaccination. Anti-SARS-CoV-2 IgA titers significantly decreased 12-14 weeks after vaccination (p = 0.02), whereas IgG titers remained stable (p = 0.2). IVIg did not significantly reduce intraindividual anti-SARS-CoV-2 IgA/IgG serum titers in immune neuropathies (p = 0.69). IVIg-derived anti-SARS-CoV-2 IgG did not alter serum anti-SARS-CoV-2 IgG decrease after IVIg administration (p = 0.67). CONCLUSIONS: Our study indicates that IVIg does not impair the antibody response to COVID-19 mRNA vaccine in a short-term observation, when administered a minimum of 2 weeks after each vaccine dose. The infusion of current IVIg preparations that contain anti-SARS-CoV-2 IgG does not significantly alter serum anti-SARS-CoV-2 IgG titers.

CIDP: Analysis of Immunomarkers During COVID-19 mRNA-Vaccination and IVIg-Immunomodulation: An Exploratory Study.

Availability of COVID-19 mRNA vaccine for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg) raises the question of whether COVID-19 mRNA vaccine influences disease activity or IVIg-mediated immunomodulation in CIDP. In this exploratory study, blood samples of CIDP patients on IVIg treatment were longitudinally analyzed before and after vaccination with a COVID-19 mRNA vaccine. A total of 44 samples of eleven patients were characterized at four timepoints by ELISA and flow cytometry in terms of immunomarkers for disease activity and IVIg-immunomodulation. Apart from a significantly lower expression of CD32b on naïve B cells after vaccination, no significant alteration of immunomarkers for CIDP or IVIg-mediated immunomodulation was observed. Our exploratory study suggests that COVID-19 mRNA vaccine does not have a relevant impact on immune activity in CIDP. In addition, immunomodulatory effects of IVIg in CIDP are not altered by COVID-19 mRNA vaccine. This study was registered in the German clinical trial register (DRKS00025759). Overview over the study design. Blood samples of CIDP patients on recurrent IVIg treatment and vaccination with a COVID-19 mRNA vaccine were obtained at four timepoints for cytokine ELISA and flow cytometry, to assess key cytokines and cellular immunomarkers for disease activity and IVIg-immunomodulation in CIDP.