scholarly journals Defects of CTLA-4 Are Associated with Regulatory T Cells in Myasthenia Gravis Implicated by Intravenous Immunoglobulin Therapy

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wenhua Xu ◽  
Mingshan Ren ◽  
Swagata Ghosh ◽  
Kai Qian ◽  
Zhaofeng Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Myasthenia Gravis ◽  
Intravenous Immunoglobulin ◽  
Ivig Therapy ◽  
Immunoglobulin Therapy ◽  
Treg Cells ◽  
Ivig Treatment ◽  
Intravenous Immunoglobulin Therapy ◽  
Circulating Autoantibodies ◽  
Antigen Presenting

Myasthenia gravis (MG) is a CD4+ T cell-dependent autoimmune disease resulting from aberrant immune response mediated by circulating autoantibodies at the neuromuscular junction. Intravenous immunoglobulin (IVIg) is an expensive and commonly used immunotherapeutic approach to treat patients with MG. The mechanisms of actions involved in IVIg treatment, however, remain to be investigated. In an effort to examine the roles of various subsets of CD4+ T cells in the periphery blood of MG and uncover the mechanisms that contribute to the therapeutical effects of IVIg, we first demonstrated that a subset of CD4+ T cells, CTLA-4-expressing regulatory T (Treg) cells, were underrepresented and functionally defective in MG patients. The dynamic profiling during the IVIg therapy course further revealed an inverse relationship between the frequency of CTLA-4+ Treg and the quantitative MG (QMG) score that represents disease severity. Our mechanistic studies indicated that IVIg expands CTLA-4-Treg cells via modulating antigen-presenting dendritic cells (DCs). To determine the molecular defects of CTLA-4 in abnormities of Treg in MG patients, we demonstrated hypermethylation at -658 and -793 CpGs of CTLA-4 promoter in MG Tregs. Interestingly, IVIg therapy significantly reduced the methylation level at these two sites in MG patients. Overall, our study may suggest a role of CTLA-4 in functionally defected Treg cells in MG and its actions involved in IVIg therapy.

scholarly journals Intravenous Immunoglobulin Therapy Restores the Quantity and Phenotype of Circulating Dendritic Cells and CD4+ T Cells in Children with Acute Kawasaki Disease

2021 ◽  
Author(s):  
Nana Wang ◽  
Zhongyue Chen ◽  
Fan Zhang ◽  
Qianwen Zhang ◽  
Ling Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Kawasaki Disease ◽  
Intravenous Immunoglobulin ◽  
Peripheral Blood ◽  
Immunoglobulin Therapy ◽  
Ivig Treatment ◽  
Intravenous Immunoglobulin Therapy ◽  
Domain 3 ◽  
Number Percentage

Abstract Background: Intravenous immunoglobulin (IVIG) is widely used to treat Kawasaki disease (KD). However, the mechanisms by which it reduces systemic inflammation are not completely understood. Dendritic cells (DCs) and T cells play critical roles in the pathogenic processes of immune disorders. Assessing the quantity of DC subsets and T cells and identifying functional molecules present on these cells, which provide information about KD, in the peripheral blood may provide new insights into the mechanisms of immunoglobulin therapy. Methods: In total, 54 patients with KD and 27 age-matched healthy controls (HCs) were included in this study. The number, percentage, and phenotype of DC subsets and CD4+ T cells in peripheral blood were analysed through flow cytometry.Results: Patients with KD exhibited fewer peripheral DC subsets and CD4+ T cells than HCs. Human leucocyte antigen-DR (HLA-DR) expression was reduced on myeloid DCs (CD1c+ mDCs), whereas that on plasmacytoid DCs (pDCs) did not change significantly. Both pDCs and CD1c+ mDCs displayed significantly reduced expression of co-stimulatory molecules, including CD40, CD86. Expression of T-cell immunoglobulin and mucin domain 3 (TIM-3) was increased on CD4+ T cells. No significant differences were observed concerning the quantity and phenotype of DC subsets and CD4+ T cells in patients with KD with and without coronary artery lesions. Importantly, these altered quantity and phenotypes on DC subsets and CD4+ T cells were restored to a great extent after IVIG treatment. T helper (Th) subsets including Th1 and Th2 among CD4+ T cells did not show alteration pre- and post-IVIG treatment, although the Th1-related cytokine IFN-γ level increased dramatically in patients with KD pre-IVIG treatment.Conclusions: pDCs and CD1c+ DCs presented an immature or tolerant phenotype in acute stages of KD, IVIG treatment restored the quantity and functional molecules of DCs and CD4+ T cells to distinct levels, indicating the involvement of DCs and CD4+ T cells in the inflammation in KD. The findings provide insights into the immunomodulatory actions of IVIG.

scholarly journals Does intravenous immunoglobulin therapy prolong immunodeficiency in transient hypogammaglobulinemia of infancy?

2013 ◽  
Vol 5 (3) ◽  
pp. 14 ◽  
Author(s):  
Lale Memmedova ◽  
Elif Azarsiz ◽  
Neslihan Edeer Karaca ◽  
Guzide Aksu ◽  
Necil Kutukculer
Keyword(s):  
Immune System ◽  
Intravenous Immunoglobulin ◽  
Ivig Therapy ◽  
Immunoglobulin Therapy ◽  
Serum Immunoglobulin ◽  
Ivig Treatment ◽  
Intravenous Immunoglobulin Therapy ◽  
Humoral Immune ◽  
Significant Difference ◽  
Ivig Replacement

Transient hypogammaglobulinemia of infancy (THI) is characterized by recurrent infections and one or more reduced serum immunoglobulin levels. Typically, THI patients recover spontaneously, mostly within 30-40 months of age, but sometimes recovery may be delayed until 5-6 years of age. The use of intravenous immunoglobulin (IVIg) as an alternative to antibiotic prophylaxis remains contraversial also in symptomatic THI patients. In fact, some authors believe that IVIg therapy may cause a delay in the maturation of the humoral immune system because of the interference from passively transfered antibodies. The aim of this study was to investigate the effect of IVIg replacement on recovery from immunodeficiency in THI patients and determine new parameters in order to include these patients in IVIg therapy groups. In this retrospective study, 43 patients (65%) received IVIg replacement therapy while 23 patients (34.8%) showed spontaneous normalization without IVIg. The percentages of patients who had more than six times the number of febrile infections in a year decreased from 91% to 21% in the group receiving IVIg treatment. At admission, before being recruited to IVIg therapy, serum immunoglobulin G (IgG) levels and anti-hemophilus B (Hib) antibody titers were found to be significantly low in cases who were selected for IVIg replacement. The percentages of patients who did not have protective levels of anti-Hib, anti-rubella or anti-rubeola-IgG were also significantly high in IVIg cases. There was no statistically significant difference in the age at which IgG levels normalized between the IVIg and the non-IVIg group. Patients in the IVIg group and non-IVIg group reached normal IgG levels at the age of 42.9±22.0 and 40.7±19.8 months, respectively. In conclusion, IVIg infusions do not cause a delay in the maturation of the immune system in THI patients. Besides the well-established criteria, very low and non-protective specific antibody responses against previously applied vaccines are important factors to consider when selecting patients for IVIg therapy.

scholarly journals VNTR2/VNTR3 genotype in the FCGRT gene is associated with reduced effectiveness of intravenous immunoglobulin in patients with myasthenia gravis

2021 ◽  
Vol 14 ◽  
pp. 175628642098674
Author(s):  
Shengyao Su ◽  
Qing Liu ◽  
Xueping Zhang ◽  
Xinmei Wen ◽  
Lin Lei ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Intravenous Immunoglobulin ◽  
Medical Records ◽  
Daily Living ◽  
Response Rate ◽  
Predictive Marker ◽  
Ivig Therapy ◽  
Variable Number ◽  
Ivig Treatment ◽  
Therapeutic Outcomes

Background: Intravenous immunoglobulin (IVIG) has been commonly used to treat myasthenia gravis exacerbation, but is still ineffective in nearly 30% of patients. A variable number of tandem repeat (VNTR) polymorphism in the FCGRT gene has been found to reduce the efficiency of IgG biologics. However, whether the polymorphism influences the efficacy of IVIG in generalized myasthenia gravis (MG) patients with exacerbations remains unknown. Methods: The distribution of VNTR genotypes was analyzed in 334 patients with MG. Varied VNTR alleles were determined by capillary electrophoresis and confirmed by Sanger sequencing. Information of endogenous IgG levels were collected in patients without previous immunotherapy ( n = 26). Medical records of patients who received IVIG therapy were retrospectively analyzed for therapeutic outcomes of IVIG treatment ( n = 61). Patients whose Activities of Daily Living scores decreased by 2 or more points on day 14 were considered responders to the treatment. Results: The VNTR3/3 and VNTR2/3 genotypes were detected in 96.7% (323/334) and 3.4% (11/334) patients, respectively. Patients with VNTR2/3 heterozygosity had lower endogenous IgG levels than those with VNTR3/3 homozygosity (9.81 ± 2.61 g/L versus 12.41 ± 2.45g/L, p = 0.016). The response rate of IVIG therapy was 78.7% (48/61). All responders and nine non-responders were VNTR3/3 homozygotes, whereas all the patients with VNTR2/3 genotypes were non-responders ( n = 4). In patients who took IVIG treatments, endogenous IgG levels were significantly lower in non-responders compared with responders (12.93 ± 2.24 g/L versus 8.85 ± 2.69 g/L, p = 0.006), especially in VNTR2/3 heterozygotes (7.86 ± 1.78 g/L, p = 0.001). Conclusion: The VNTR2/3 genotype could influence endogenous IgG levels and serve as a predictive marker for poor responses to IVIG in MG patients.

ACUTE CORONARY SYNDROME FOLLOWING INTRAVENOUS IMMUNOGLOBULIN THERAPY : A HIDDEN RISK

2021 ◽  
pp. 78-79
Author(s):  
Karthikkeyan Rajachandran ◽  
Giphy Susan Varghese
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Intravenous Immunoglobulin ◽  
Ivig Therapy ◽  
Immunoglobulin Therapy ◽  
Left Ventricular ◽  
Intravenous Immunoglobulin Therapy ◽  
Severe Left Ventricular Dysfunction ◽  
St Segment Elevation ◽  
Coronary Syndrome

Intravenous immunoglobulin (IVIG) is one of the main line modalities of therapy for chronic inammatory demyelinating polyneuropathy (CIDP). We hereby, report an incidence of acute myocardial infarction probably induced by IVIG during the treatment of CIDP. A 76 year old female with no history suggestive of cardiovascular disease, developed an acute Non ST Segment Elevation Myocardial Infarction (NSTEMI) and severe left ventricular dysfunction after receiving three doses of IVIG. Since hypercoagulability is a concern with IVIG therapy, it was discontinued. Hence, we highlight the importance of cardiac evaluation before initiation and during the course of IVIG therapy in elderly patients as well as in patients with known risk factors for cardiovascular disease and thrombotic events.

High-dose intravenous immunoglobulin therapy for myasthenia gravis

1997 ◽  
Vol 245 (1) ◽  
pp. 26-31 ◽  
Author(s):  
J. L. M. Jongen ◽  
P. A. van Doorn ◽  
Frans G. A. van der Meché
Keyword(s):  
Myasthenia Gravis ◽  
Intravenous Immunoglobulin ◽  
Immunoglobulin Therapy ◽  
High Dose ◽  
Intravenous Immunoglobulin Therapy

scholarly journals High-dose intravenous immunoglobulin therapy induces and maintains complete remission for polyarteritis nodosa

2014 ◽  
Vol 1 (1) ◽  
pp. 13
Author(s):  
Kazu Ode ◽  
Yoshinori Taniguchi ◽  
Yoshitaka Kumon ◽  
Yoshio Terada
Keyword(s):  
Complete Remission ◽  
Intravenous Immunoglobulin ◽  
Polyarteritis Nodosa ◽  
Alternative Therapy ◽  
Ivig Therapy ◽  
Immunoglobulin Therapy ◽  
High Dose ◽  
Intravenous Immunoglobulin Therapy ◽  
First Line Therapy ◽  
High Dose Ivig

We report a case of successful high-dose intravenous immunoglobulin (IVIG) use in a patient with refractory polyarteritis nodosa (PAN). Treatments with prednisolone (PSL) and various types of immunosuppressants including methotrexate (MTX) and intravenous cyclophosphamide (IVCY) were unsuccessful, and then, high-dose IVIG therapy was added. High-dose IVIG therapy improved all symptoms including high fever, arthralgia, mononeuritis multiplex and indurated erythema due to PAN. Moreover, serum inflammatory markers were also normalized. High-dose IVIG is maintaining complete remission for PAN without flare-up for additional 4 years. Therefore, high-dose IVIG therapy might be considered as a first-line therapy in patients with PAN or alternative therapy in refractory PAN.

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