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  1. Article: Regulatory T Cell-Targeted Immunomodulatory Therapy for Long-Term Clinical Improvement of Atopic Dermatitis: Hypotheses and Perspectives.

    Nahm, Dong-Ho

    Life (Basel, Switzerland)

    2023  Volume 13, Issue 8

    Abstract: Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disorder characterized by itching and eczematous lesions. It is often associated with a personal or familial history of allergic diseases. Allergic inflammation induced by immunoglobulin ...

    Abstract Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disorder characterized by itching and eczematous lesions. It is often associated with a personal or familial history of allergic diseases. Allergic inflammation induced by immunoglobulin E and T-helper type 2 (Th2) cell responses to common environmental agents has been suggested to play an essential role in AD pathogenesis. The standard therapies for AD, including topical or systemic agents, focus on controlling skin inflammation. Recently developed monoclonal antibody to interleukin-4 receptor alpha or Janus kinase inhibitors can provide significant clinical improvements in patients with AD by inhibiting Th2 cell-mediated skin inflammation. However, the clinical efficacy of the Th2 cell-targeted therapy is transient and incomplete in patients with AD. Patients with AD are seeking a permanent cure. Therefore, the development of novel immunomodulatory strategies that can improve a long-term clinical outcome and provide a long-term treatment-free clinical remission of AD (disease-modifying therapy) is needed. Regulatory T (Treg) cells play a critical role in the maintenance of immune tolerance and suppress the development of autoimmune and allergic diseases. This review provides three working hypotheses and perspectives for the treatment of AD by Treg cell activation. (1) A decreased number or function of Treg cells is a critical event that causes the activation of Th2 cells, leading to the development and maintenance of AD. (2) Activation of Treg cells is an effective therapeutic approach for AD. (3) Many different immunomodulatory strategies activating Treg cells can provide a long-term clinical improvement of AD by induction of immune tolerance. The Treg cell-targeted immunomodulatory therapies for AD include allergen immunotherapy, microbiota, vitamin D, polyvalent human immunoglobulin G, monoclonal antibodies to the surface antigens of T cell or antigen-presenting cell, and adoptive transfer of autologous Treg cells or genetically engineered Treg cells expanded in vitro.
    Language English
    Publishing date 2023-08-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life13081674
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Mechanism underlying polyvalent IgG-induced regulatory T cell activation and its clinical application: Anti-idiotypic regulatory T cell theory for immune tolerance.

    Victor, Jefferson Russo / Nahm, Dong-Ho

    Frontiers in immunology

    2023  Volume 14, Page(s) 1242860

    Abstract: The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions ... ...

    Abstract The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions to external antigens. Reduction in the number or function of Treg cells has been suggested as a key immune abnormality underlying the development of autoimmune and allergic diseases.
    MeSH term(s) Humans ; T-Lymphocytes, Regulatory ; Interleukin-10/metabolism ; Immunoglobulin G/metabolism ; Immune Tolerance ; Allergens ; Hypersensitivity/metabolism ; Autoimmune Diseases/therapy ; Autoimmune Diseases/metabolism ; Autoantigens/metabolism
    Chemical Substances Interleukin-10 (130068-27-8) ; Immunoglobulin G ; Allergens ; Autoantigens
    Language English
    Publishing date 2023-11-29
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1242860
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Associations of Atopic Dermatitis With Obesity and Unmarried Status in Young Adults: Evidence for Atopic Dermatitis as a Life-Style Disorder With High Social Impact.

    Nahm, Dong Ho

    Allergy, asthma & immunology research

    2016  Volume 8, Issue 2, Page(s) 89–91

    Language English
    Publishing date 2016-01-06
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2545725-1
    ISSN 2092-7363 ; 2092-7355
    ISSN (online) 2092-7363
    ISSN 2092-7355
    DOI 10.4168/aair.2016.8.2.89
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Personalized Immunomodulatory Therapy for Atopic Dermatitis: An Allergist's View.

    Nahm, Dong-Ho

    Annals of dermatology

    2015  Volume 27, Issue 4, Page(s) 355–363

    Abstract: The current standard medical therapy for atopic dermatitis (AD) mainly focuses on symptomatic relief by controlling skin inflammation with topical corticosteroids and/or topical calcineurin inhibitors. However, the clinical efficacy of pharmacological ... ...

    Abstract The current standard medical therapy for atopic dermatitis (AD) mainly focuses on symptomatic relief by controlling skin inflammation with topical corticosteroids and/or topical calcineurin inhibitors. However, the clinical efficacy of pharmacological therapy is often disappointing to both patients and physicians. The terminology of AD contains a historical meaning of eczematous dermatitis caused by hypersensitivity reaction to environmental inhalant or food allergen. Complex interrelationships among genetic abnormalities, environmental triggers, skin barrier defects, and immune dysfunction resulting in a vicious domino-circle seem to be involved in the development and maintenance of AD. In the viewpoint of AD as an allergic disease, complete avoidance of clinically relevant allergen or induction of specific immune tolerance through administrations of allergen (allergen immunotherapy) can provide clinical remission by breaking the vicious domino-circle maintaining a chronic disease state. In recent clinical studies, monoclonal antibodies including the anti-interleukin-4 receptor antibody and anti-B cell antibody induced significant clinical improvements in patients with AD. The detailed characteristics of immune dysfunction are heterogeneous among patients with AD. Therefore, a personalized combination of immunomodulatory therapies to reduce hypersensitivity (allergen immunotherapy) and correct immune dysfunction (monoclonal antibody therapy) could be a reasonable therapeutic approach for patients with AD. Future immunomodulatory therapies for AD should be developed to achieve long-term treatment-free clinical remission by induction of immune tolerance.
    Language English
    Publishing date 2015-07-29
    Publishing country Korea (South)
    Document type Journal Article ; Review
    ZDB-ID 1012662-4
    ISSN 2005-3894 ; 1013-9087
    ISSN (online) 2005-3894
    ISSN 1013-9087
    DOI 10.5021/ad.2015.27.4.355
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study.

    Lee, Hyun-Young / Jeon, Hyun-Seob / Jang, Jae-Hyuk / Lee, Youngsoo / Shin, Yoo Seob / Nahm, Dong-Ho / Park, Hae-Sim / Ye, Young-Min

    The journal of allergy and clinical immunology. Global

    2024  Volume 3, Issue 2, Page(s) 100245

    Abstract: Background: Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear.: Objective: Our aim was to evaluate the real-world effectiveness of ... ...

    Abstract Background: Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear.
    Objective: Our aim was to evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors.
    Methods: Initially, 5535 patients with CU who were receiving at least 20 mg of loratadine daily for at least 6 months (January 2007-August 2021) were screened. Ultimately, 386 patients who had been receiving omalizumab add-on treatment for >6 months were followed-up for more than 2 years. Predictors of treatment response to omalizumab add-on therapy for patients with antihistamine-refractory CU were identified by using a generalized linear model.
    Results: In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for patients with H1AH-refractory CU. Analysis of longitudinal responses to omalizumab treatment revealed 3 distinct clusters: favorable (cluster 1 [n = 158]), intermediate (cluster 2 [n =1 43]), and poor responses (cluster 3 [n = 85]). Subjects were categorized on the basis of whether they had achieved a complete response within 3 months; 213 early responders, 117 late responders, and 56 nonresponders were identified. The initial dose of omalizumab differed significantly among the 3 clusters. Low total IgE level (<40 kU/L) predicted nonresponse (odds ratio [OR] = 3.10 [
    Conclusion: Real-world data reveal 3 distinct clusters for response to omalizumab treatment; confirm low serum total IgE level (<40 kU/L) as a predictor of nonresponse; and identify potential biomarkers, including IgE level, basophil count, and PLR, for early responders.
    Language English
    Publishing date 2024-03-19
    Publishing country United States
    Document type Journal Article
    ISSN 2772-8293
    ISSN (online) 2772-8293
    DOI 10.1016/j.jacig.2024.100245
    Database MEDical Literature Analysis and Retrieval System OnLINE

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

    Nahm, Dong-Ho / Kim, Myoung-Eun / Kwon, Byul / Kim, Ji Su / Park, Bumhee

    Yonsei medical journal

    2023  Volume 64, Issue 7, Page(s) 423–432

    Abstract: 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 ... ...

    Abstract 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%,
    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).
    MeSH term(s) Humans ; Adult ; Adolescent ; Dermatitis, Atopic/therapy ; Injections, Intramuscular ; Treatment Outcome ; Double-Blind Method ; Severity of Illness Index
    Language English
    Publishing date 2023-06-27
    Publishing country Korea (South)
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 303740-x
    ISSN 1976-2437 ; 0513-5796
    ISSN (online) 1976-2437
    ISSN 0513-5796
    DOI 10.3349/ymj.2022.0559
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Real Clinical Practice Data of Monthly Dupilumab Therapy in Adult Patients With Moderate-to-Severe Atopic Dermatitis: Clinical Efficacy and Predictive Markers for a Favorable Clinical Response.

    Lee, Youngsoo / Kim, Myoung-Eun / Nahm, Dong-Ho

    Allergy, asthma & immunology research

    2021  Volume 13, Issue 5, Page(s) 733–745

    Abstract: Purpose: Dupilumab is recommended to be administered biweekly to treat adult patients with moderate-to-severe atopic dermatitis (AD). Real clinical practice data on the clinical efficacy of monthly dupilumab therapy are limited. We analyzed real ... ...

    Abstract Purpose: Dupilumab is recommended to be administered biweekly to treat adult patients with moderate-to-severe atopic dermatitis (AD). Real clinical practice data on the clinical efficacy of monthly dupilumab therapy are limited. We analyzed real clinical practice data on the clinical efficacy of monthly dupilumab therapy and predictive markers for favorable clinical responses to the therapy.
    Methods: Medical records of 57 adult patients with moderate-to-severe AD who received dupilumab therapy every 4 weeks for 16 weeks were analyzed retrospectively. Eczema Area and Severity Index (EASI) were recorded at baseline and week 16. Clinical responses to monthly dupilumab therapy were defined as the proportion of patients with decreased EASI scores of at least 50% or 75% from baseline at week 16 (EASI-50 or EASI-75). Blood eosinophil counts and serum lactate dehydrogenase (LDH) levels were measured at baseline and week 16.
    Results: Monthly dupilumab therapy showed EASI-50 and EASI-75 clinical responses in 48 (84.2%) and 27 (47.4%) of 57 patients at week 16, respectively. The percentage decrease in EASI scores from baseline at week 16 was significantly inversely correlated with baseline blood eosinophil count (correlation coefficient [
    Conclusions: Monthly dupilumab therapy was clinically effective in adult patients with moderate-to-severe AD in real clinical practice. Baseline blood eosinophil count and serum LDH level could be predictive markers for clinical response to dupilumab therapy.
    Language English
    Publishing date 2021-09-05
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2545725-1
    ISSN 2092-7363 ; 2092-7355
    ISSN (online) 2092-7363
    ISSN 2092-7355
    DOI 10.4168/aair.2021.13.5.733
    Database MEDical Literature Analysis and Retrieval System OnLINE

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

    Kwon, Byul / Yang, Seung-Jung / Cho, Su-Mi / Kim, Myoung-Eun / Nahm, Dong-Ho

    Medicine

    2022  Volume 101, Issue 22, Page(s) e29486

    Abstract: 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 ... ...

    Abstract 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).
    MeSH term(s) Adult ; Cytokines ; Humans ; Immunoglobulin G ; Immunomodulation ; Interferon-gamma ; Interleukin-10 ; Prospective Studies ; Research Subjects
    Chemical Substances Cytokines ; Immunoglobulin G ; Interleukin-10 (130068-27-8) ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2022-06-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80184-7
    ISSN 1536-5964 ; 0025-7974
    ISSN (online) 1536-5964
    ISSN 0025-7974
    DOI 10.1097/MD.0000000000029486
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Immunomodulatory effects induced by intramuscular administration of autologous total immunoglobulin G in patients with atopic dermatitis.

    Cho, Su-Mi / Kim, Myoung-Eun / Kwon, Byul / Nahm, Dong-Ho

    International immunopharmacology

    2017  Volume 52, Page(s) 1–6

    Abstract: 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 ... ...

    Abstract 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.
    Language English
    Publishing date 2017-11
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2017.08.020
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  10. Article ; Online: Effects of Intramuscular Injection of Autologous Immunoglobulin on Clinical Severity and Serum IgE Concentration in Patients with Atopic Dermatitis.

    Nahm, Dong-Ho / Kim, Myoung-Eun / Cho, Su-Mi

    Dermatology (Basel, Switzerland)

    2015  Volume 231, Issue 2, Page(s) 145–151

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Adolescent ; Adult ; Dermatitis, Atopic/blood ; Dermatitis, Atopic/therapy ; Female ; Humans ; Immunoglobulin E/blood ; Immunoglobulin G/administration & dosage ; Immunologic Factors/administration & dosage ; Immunotherapy ; Injections, Intramuscular ; Lymphocyte Count ; Male ; Severity of Illness Index ; Young Adult
    Chemical Substances Immunoglobulin G ; Immunologic Factors ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2015
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1099692-8
    ISSN 1421-9832 ; 1018-8665
    ISSN (online) 1421-9832
    ISSN 1018-8665
    DOI 10.1159/000431173
    Database MEDical Literature Analysis and Retrieval System OnLINE

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