Intramuscular administration of autologous total immunoglobulin G induces immunomodulatory effects on T cells in healthy human subjects: An open-labeled prospective single-arm trial.

BACKGROUND: We hypothesized that intramuscular administration of autologous total immunoglobulin G (IgG) could induce an immunomodulatory effect in human subjects. In our previous studies, we showed that intramuscular administration of autologous total IgG could induce significant clinical improvements and increases of the serum levels of interleukin-10 (IL-10) and interferon-gamma (IFN-γ) in patients with atopic dermatitis. OBJECTIVE: To investigate the mechanism of immunomodulation induced by intramuscular administration of autologous total IgG, we evaluated changes in T cells before and after intramuscular administrations of autologous total IgG in this study. METHODS: Thirteen healthy adults received 8 intramuscular injections of 50 mg autologous total IgG for 4 weeks (from week 0 to week 4). The percentages of IL-10- or IFN-γ-producing peripheral blood T cells, as well as serum levels of IL-10, IFN-γ, and immunoglobulins, were measured at baseline (week 0) and at weeks 4, 8, and 12. RESULTS: The percentage of IL-10-producing CD4+ T cells was significantly increased at weeks 8 and 12 compared to baseline (P < .05), while the percentage of IFN-γ-producing CD3+ T cells was significantly increased at week 12 compared to baseline (P < .05). There were no significant differences in the serum levels of IL-10, IFN-γ, and immunoglobulins before and after intramuscular administration of autologous total IgG (P > .05). No serious adverse events were observed. CONCLUSION: Intramuscular administration of autologous total IgG induced immunomodulatory effects on T cells in healthy human subjects. This simple intervention could be a safe, effective, and economical T cell immunomodulation method for human subjects (NCT03695757).

Efficacy, Safety, and Immunomodulatory Effect of the Intramuscular Administration of Autologous Total Immunoglobulin G for Atopic Dermatitis: A Randomized Clinical Trial.

PURPOSE: The management of patients with atopic dermatitis (AD) is often difficult. We hypothesized that repeated intramuscular administration of autologous total immunoglobulin G (IgG) could induce clinical improvement in patients with AD through immune modulation. This clinical trial was conducted to evaluate the efficacy, safety, and immunomodulatory effect of the intramuscular administration of autologous total IgG in patients with AD. METHODS: In this randomized, double-blind, placebo-controlled trial, 51 adolescent and adult patients with moderate-to-severe AD were randomized to receive 8 weekly intramuscular administrations of autologous total IgG 50 mg (n = 26) or saline (n = 25) over a 7-week period and were followed up to week 16. Changes in the clinical severity score (Eczema Area and Severity Index), affected body surface area, patient-reported Dermatology Life Quality Index (DLQI) score, laboratory biomarkers, and incidence of adverse events from baseline to week 16 were assessed. RESULTS: The intramuscular administration of autologous total IgG, compared with saline, decreased the clinical severity score (-64.8% vs. -20.3%, P < 0.001), reduced the affected body surface area (-53.9% vs. -19.1%, P < 0.001), improved the DLQI score (-35.4% vs. -14.4%, P = 0.015), increased serum interleukin-10 and interferon-γ levels (P = 0.011 and P = 0.003, respectively), and reduced the incidence of AD exacerbation (11.5% vs. 48.0%, P = 0.004) from baseline to week 16. No serious adverse events were observed. CONCLUSIONS: The intramuscular administration of autologous total IgG provided clinical improvements and a systemic immunomodulatory effect in adolescent and adult patients with moderate-to-severe AD without significant side effects. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0001597.

Immunomodulatory effects induced by intramuscular administration of autologous total immunoglobulin G in patients with atopic dermatitis.

BACKGROUND: Polyvalent human immunoglobulin G (IgG) preparations produced from the plasma pools of healthy blood donors have been used for the treatment of various autoimmune diseases and allergic diseases because of their anti-inflammatory and immunomodulatory effects. We hypothesized that intramuscular administration of autologous total IgG would induce immunomodulatory effects in patients with allergic diseases, based on the clinical efficacy of autologous blood therapy in patients with atopic dermatitis (AD). METHODS: Sixteen adult AD patients with IgE-mediated sensitization to the house dust mite (Dermatophagoides farinae) received intramuscular injections of 50 mg autologous total IgG twice a week for 4 weeks. The serum levels of IgE, IgG, and IgG4 antibodies to the recombinant group 2 major allergen of Dermatophagoides farinae (Der f 2) and serum levels of interleukin (IL)-10, IL-4, IL-12, and interferon gamma (IFN-γ) were measured by enzyme-linked immunosorbent assay at baseline and at weeks 4, 8, and 12. RESULTS: The serum level of IgE antibodies to Der f 2 was significantly decreased at 12 weeks compared with baseline (p<0.005). The serum levels of IgG and IgG4 antibodies to Der f 2 were significantly increased at 4, 8, and 12 weeks compared with baseline (p<0.05). The serum levels of IL-10 and IFN-γ were significantly increased at 4, 8, and 12 weeks compared with baseline (p<0.05). There were no significant differences in the serum levels of IL-4 or IL-12 before and after intramuscular administrations of autologous total IgG (p>0.05). CONCLUSION: Intramuscular administration of autologous total IgG induced anti-allergic immunomodulatory effects in AD patients. Further studies are required to evaluate the detailed immunological mechanism underlying these effects.

Clinical Efficacy of Subcutaneous Allergen Immunotherapy in Patients with Atopic Dermatitis.

PURPOSE: The clinical usefulness of subcutaneous allergen immunotherapy (SCIT) in the treatment of atopic dermatitis (AD) is still controversial. We analyzed the clinical efficacy of SCIT in patients with AD and the clinical characteristics of patients showing a favorable clinical response to the treatment. MATERIALS AND METHODS: Two hundred and fifty one patients with AD sensitized to house dust mite (HDM) were treated by SCIT using HDM extract. The clinical severity of AD was measured using the standardized clinical severity scoring system for AD (SCORAD) at baseline and 12 months. A favorable clinical response to SCIT was defined as a decrease in SCORAD value at 12 months greater than 50% compared to baseline value. Severe AD was defined as a baseline SCORAD value above 50. RESULTS: A favorable clinical response to SCIT was observed in 73.6% of patients. The proportion of patients showing a favorable clinical response to SCIT was significantly higher in patients with severe AD (90.6%) than patients with mild to moderated AD (63.7%) (p<0.001). Patients with severe AD showing a favorable clinical response had a significantly shorter duration of AD (12.3±8.5 years; mean±SD) than patients with severe AD showing no significant clinical response (20.6±10.9 years) (p<0.05) at baseline. CONCLUSION: SCIT could be a clinically useful therapeutic option for patients with severe AD sensitized to HDM. Early initiation of SCIT might provide a favorable clinical outcome in patients with severe AD sensitized to HDM.

Autologous Immunoglobulin Therapy in Patients With Severe Recalcitrant Atopic Dermatitis: Long-Term Changes of Clinical Severity and Laboratory Parameters.

This report evaluated long-term changes in clinical severity and laboratory parameters in 3 adult patients with severe recalcitrant atopic dermatitis (AD) who were treated with intramuscular injections of 50 mg of autologous immunoglobulin G (IgG) twice a week for 4 weeks (autologous immunoglobulin therapy, AIGT) and followed up for more than 2 years after the treatment. We observed the following 4 major findings in these 3 patients during the long-term follow-up after AIGT. (1) Two of the 3 patients showed a long-term clinical improvement for more than 36 weeks after AIGT with a maximum decrease in clinical severity score greater than 80% from baseline. (2) These 2 patients also showed long-term decreases in serum total IgE concentrations and peripheral blood eosinophil count for more than 36 weeks after AIGT with a maximum decrease in the two laboratory parameters of allergic inflammatory greater than 70% from baseline. (3) No significant side effect was observed during the 2 years of follow-up period after the AIGT in all 3 patients. (4) Serum levels of IgG anti-idiotype antibodies to the F(ab')2 fragment of autologous IgG administered for the treatment were not significantly changed after AIGT in all 3 patients. These findings suggest that AIGT has long-term favorable effects on both clinical severity and laboratory parameters in selected patients with severe recalcitrant AD. Further studies are required to evaluate the clinical usefulness and therapeutic mechanism of AIGT for AD.

Effects of Intramuscular Injection of Autologous Immunoglobulin on Clinical Severity and Serum IgE Concentration in Patients with Atopic Dermatitis.

BACKGROUND/OBJECTIVE: The management of patients with atopic dermatitis (AD) is often difficult for both patients and physicians. We hypothesized that repeated intramuscular injections of autologous immunoglobulin can induce clinical improvement in patients with AD by correcting immune dysfunction. METHODS: Seventeen adult patients with severe AD were treated by intramuscular injection of 50 mg autologous immunoglobulin (mainly IgG with a purity ≥97%) twice a week for 4 weeks. The standardized clinical severity scoring system for AD (SCORAD) value and serum IgE concentration were measured at baseline and at 4, 8, and 12 weeks. RESULTS: SCORAD values and serum IgE concentrations significantly decreased at 4, 8, and 12 weeks compared to baseline (p < 0.05). No significant side effects were observed. CONCLUSIONS: Repeated intramuscular injections of autologous immunoglobulin significantly decreased the clinical severity and serum IgE concentration in patients with severe AD. Further studies are required to evaluate the clinical significance of these findings.

Autologous immunoglobulin therapy in patients with severe recalcitrant atopic dermatitis: a preliminary report.

The management of severe recalcitrant atopic dermatitis (AD) is a challenging issue for clinicians and patients. We hypothesized that repeated intramuscular injections of autologous immunoglobulin (autologous immunoglobulin therapy: AIGT) might induce clinical improvements in patients with AD by stimulation of the active immune response to antigen-binding-site of pathogenic antibodies. We tried AIGT in 3 adult patients with severe recalcitrant AD whose clinical conditions could not be effectively controlled by medical treatments (including oral cyclosporine) for more than 2 years. Autologous immunoglobulin was purified from the autologous plasma by affinity chromatography using Protein A. The patients were treated by an intramuscular injection of 50 mg of autologous immunoglobulin twice a week for 4 weeks. A clinical severity score of AD (SCORAD value) showed a decrease greater than 30% at 8 weeks after the initiation of AIGT compared with the baseline before the initiation of AIGT in all 3 patients with severe recalcitrant AD. No significant side effects from treatment were observed. Further studies with larger numbers of patients are required to evaluate the clinical usefulness of AIGT for AD.

Clinical efficacy of autologous plasma therapy for atopic dermatitis.

BACKGROUND: The clinical efficacy of autologous blood therapy (ABT) in patients with atopic dermatitis (AD) was demonstrated by a randomized double-blind placebo-controlled study. To characterize the blood component mediating the therapeutic efficacy of ABT for AD, we evaluated the clinical efficacy of autologous plasma therapy (APT) and autologous high-molecular-weight plasma protein fraction therapy (AHPT) in patients with AD in this study. METHODS: A total of 22 patients with recalcitrant AD were treated with 8 weekly intramuscular injections of either autologous plasma (n = 11) or autologous high-molecular-weight plasma protein fraction (n = 11) for 7 weeks. RESULTS: The clinical severity score of AD (SCORAD value) of 11 patients who completed AHPT significantly decreased from 79.7 ± 17.0 (mean ± SD) at baseline to 65.8 ± 16.4 at 6 weeks and 60.1 ± 16.0 at 7 weeks (Wilcoxon signed-rank test, p < 0.05). There were no significant differences among the SCORAD values measured at baseline (74.2 ± 19.6), at 6 weeks (66.3 ± 23.6) and at 7 weeks (67.5 ± 20.8) in 10 patients who completed APT (p > 0.05). CONCLUSION: This result suggests that the blood component mediating the therapeutic efficacy of ABT in patients with AD might be present in the high-molecular-weight plasma protein fraction.