Intramuscular Injection of Autologous Serum in Adolescent and Adult Patients with Atopic Dermatitis: A Preliminary Randomized Clinical Trial.

PURPOSE: The favorable clinical efficacies of intramuscular injection of autologous blood in patients with atopic dermatitis (AD) and intramuscular injection of autologous serum in patients with chronic urticaria have been demonstrated by randomized clinical trials. In this study, we assessed the clinical effectiveness and safety of the intramuscular injection of autologous serum in patients with AD. MATERIALS AND METHODS: In this randomized, placebo-controlled, and double-blind trial, 23 adolescent and adult patients with moderate-to-severe AD were enrolled. The patients were randomized to receive eight intramuscular injections of 5 mL of autologous serum (n=11) or saline (n=12) over 4 weeks, and were followed up until week 8. Changes in the clinical severity scores of AD assessed by SCORing Atopic Dermatitis (SCORAD), patient-reported Dermatology Life Quality Index (DLQI) score, and incidence of adverse events were assessed from baseline to week 8. RESULTS: One patient in the treatment group and two patients in the placebo group were lost to follow-up before week 8. The intramuscular administration of autologous serum, compared with saline, decreased the SCORAD clinical severity score (-14.8% vs. 10.7%, p=0.006) and improved the DLQI score (-32.6% vs. 19.5%, p=0.01) from baseline to week 8. Serious adverse events were not observed. CONCLUSION: Intramuscular injection of autologous serum may be effective in treating AD. Further studies are needed to evaluate the clinical usefulness of this intervention for AD (KCT0001969).

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.

Increased IgG antibody-induced cytotoxicity against airway epithelial cells in patients with nonallergic asthma.

BACKGROUND: IgG autoantibodies to airway epithelial cell proteins have been detected in patients with nonallergic asthma. OBJECTIVE AND METHODS: To evaluate the functional significance of these autoantibodies, we examined the presence of IgG antibody-induced cytotoxicity against airway epithelial cells (A549) by the microcytotoxicity assay using IgG antibodies purified from patients with nonallergic asthma. RESULTS: IgG antibody-induced cytotoxicity (expressed as percent cell lysis) was significantly increased in nine patients with nonallergic asthma (mean +/- standard deviation; 30.6 +/- 7.3%) as compared with eight healthy controls (13.9 +/- 5.1%) and nine patients with allergic asthma (20.3 +/- 10.4%; p < 0.05). In addition, IgG antibody-induced cytotoxicity was significantly inhibited when IgG antibodies from patients with nonallergic asthma were pre-incubated with recombinant human airway epithelial cell autoantigens (cytokeratin 18 or alpha-enolase proteins; p < 0.05). CONCLUSION: These results suggest a possible involvement of IgG autoantibody-induced cytotoxicity against airway epithelial cells in the pathogenesis of nonallergic asthma.

Isotype and IgG subclass distribution of autoantibody response to alpha-enolase protein in adult patients with severe asthma.

PURPOSE: A possible involvement of autoimmune mechanism in the pathogenesis of bronchial asthma has been proposed. Recently, alpha-enolase protein was identified as a major autoantigen recognized by circulating IgG autoantibodies in patients with severe asthma. To evaluate a possible pathogenetic significance of these autoantibodies in severe asthma, isotype (IgG, IgA, IgM, and IgE) and IgG subclass (IgG1, IgG2, IgG3, and IgG4) distributions of autoantibodies to recombinant human alpha-enolase protein were analyzed. PATIENTS AND METHODS: We examined serum samples from 10 patients with severe asthma and 7 patients with mild-to-moderate asthma, and 5 healthy controls by immunoblot analysis. Severe asthma was defined as patients having at least 1 severe asthmatic exacerbation requiring an emergency department visit or admission in the last year despite continuous typical therapies. RESULTS: IgG1 was the predominant IgG subclass antibody response to alpha-enolase protein in patients with severe asthma. IgG1 autoantibody to alpha-enolase protein was detected in 7 of 10 patients with severe asthma (70%), 1 of 7 patients with mild-to-moderate asthma (14.3%), and none of 5 healthy controls (0%) (chi-square test; p < 0.05). IgA, IgM, and IgE autoantibodies to alpha-enolase protein could not be detected in patients with severe asthma. CONCLUSION: IgG1 subclass was the predominant type of autoantibody response to alpha-enolase protein in patients with severe asthma, suggests a possibility of IgG1 autoantibody-mediated complement activation in the pathogenesis of severe asthma.