Danazol increases T regulatory cells in patients with aplastic anemia

Khurana, Harshit; Malhotra, Pankaj; Sachdeva, Man Updesh Singh; Varma, Neelam; Bose, Parveen; Yanamandra, Uday; Varma, Subhash; Khadwal, Alka; Lad, Deepesh; Prakash, Gaurav

doi:10.1080/10245332.2018.1435045

Cited by 12 publications

(5 citation statements)

References 22 publications

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“…On the other hand, androgens induce Tregs: androgen-activated AR bound androgen response elements on the Foxp3 promoter and enhanced the acetylation of histone H4 on the promoter, allowing the binding of additional transcription factors, and thus enhanced the expression of Foxp3 in human T cells [55]. Danazol, an attenuated androgen, increased CD4+CD25highCD127lowFoxp3+ Tregs in patients with aplastic anemia [58].…”

Section: The Effects Of Sex Hormones On Immune Responsesmentioning

confidence: 99%

The Roles of Sex Hormones in the Course of Atopic Dermatitis

Kanda

Hoashi

Saeki

2019

IJMS

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Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by T helper 2 cell (Th2)-shifted abnormal immunity, skin barrier impairment, and pruritus. The prevalence of AD in childhood is slightly higher in boys than in girls; after puberty, the sexual difference is reversed. The female preponderance in all generations exists in intrinsic AD with enhanced Th1 activity and nickel allergy, lacking increased serum IgE or filaggrin mutation. AD is often deteriorated before menstruation. We review the effects of sex hormones on immune responses and skin permeability barrier and propose possible hypotheses for the above phenomena. After puberty, the immune responses of patients are remarkably influenced by sex hormones. Estrogen and progesterone enhance the activities of Th2/regulatory T cell (Treg) but suppress Th1/Th17. Androgens suppress Th1/Th2/Th17 and induce Treg. The skin permeability barrier is fortified by estrogen but is impaired by progesterone and androgens. Dehydroepiandrosterone suppresses Th2 but enhances Th1. The amount of steroid sulfatase converting dehydroepiandrosterone sulfate to dehydroepiandrosterone is higher in women than in men, and thus, women might be more susceptible to the influence of dehydroepiandrosterone. The balance of modulatory effects of sex hormones on immune responses and skin barrier might regulate the course of AD.

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Section: The Effects Of Sex Hormones On Immune Responsesmentioning

confidence: 99%

The Roles of Sex Hormones in the Course of Atopic Dermatitis

Kanda

Hoashi

Saeki

2019

IJMS

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“…Conventional PCR remained negative until the end of follow-up, 23 months after danazol interruption. The pivotal role of danazol in increasing the low levels of Treg cells reported in AA patients [ 5 ] perhaps contributes to restoring T lymphocyte and macrophage functions, the main effector cell to control parasite growth and revert PCR to negative. In addition, experimental infections in mice have shown the crucial role of myeloid-derived suppressor cells in controlling inflammation during acute Chagas disease [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Immune dysfunction is expressed by an altered number of lymphocyte subsets, increased effects of cytotoxic lymphocytes on hematopoietic stem and progenitor cells (HSPC), and low percentages of NK cells. In parallel, genetic background and intrinsic deficiencies of the HSPC, evidenced by somatic mutations such as shortened telomeres and viral infection, may also be associated with AA pathogenesis [ 1 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Aplastic Anemia and Chagas Disease: T. cruzi Parasitemia Monitoring by Quantitative PCR and Preemptive Antiparasitic Therapy

et al. 2022

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Background: Aplastic anemia is a rare and life-threatening condition, seldomly witnessed concomitantly with Chagas disease. We aim to discuss the management of these patients under risk of chronic Chagas disease reactivation (CDR), a severe condition with a high morbimortality that occurs in chronic Chagas disease patients under immunosuppression. Case reports: Trypanosoma cruzi (T. cruzi) parasitemia was monitored in three patients for 4–58 months by conventional PCR (cPCR), quantitative PCR (qPCR), microhematocrit/buffy coat, blood culture, and/or xenodiagnosis. One patient received antiparasitic treatment (benznidazole) and the other received allopurinol. Although parasitemia was controlled during and after benznidazole treatment at 300 mg/d for 51 days, in one patient, hematologic parameters worsened continuously before, during, and after treatment. Allopurinol led only to the temporary suppression of T. cruzi parasitemia in the second patient, but after danazol and hematological improvement, parasitemia became undetectable until the end of monitoring. Discussion and Conclusion: Unexpected undetectable or low parasitemia by cPCR/qPCR was reported. We show that the monitoring of parasitemia by qPCR and the use of preemptive therapy when the parasitemia was positive proved to be beneficial to our patients. As a result of the toxicity of more effective antiparasitics, shorter regimens of benznidazole or less toxic drugs in preemptive therapy are options that deserve future studies.

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“…Anabolic steroids have long been used to treat AA. Its mechanisms include increasing telomerase (TERT) gene expression in hematopoietic cells [26], stimulating erythroid progenitor [27], and enhancing regulatory T-cell [28]. The responses to anabolic steroids are varied, ranging from 25 to 56%, depending on the severity of AA and the treatment combination [29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Adult aplastic anemia in Thailand: incidence and treatment outcome from a prospective nationwide population-based study

et al. 2021

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The incidence and outcomes of aplastic anemia (AA) in Asia remain limited. This study aimed to explore the incidence and outcomes of patients with adult AA across the country of Thailand. This is a prospective multi-center nationwide population-based observational study of AA patients aged at least 15 years old, diagnosed from August 2014 to July 2016, with a longitudinal follow-up period over 2 years. There were 348 newly diagnosed adult AA patients during the enrollment period, giving an annual incidence of 4.6 per million. The incidence of severe (SAA) and very severe aplastic anemia (VSAA) (3.8 per million) was higher than non-severe AA (NSAA, 0.8 per million). The peak incidence was observed in the patients aged from 80 to 89 years old (14.4 per million). The 2-year overall survival (OS) in NSAA, SAA, and VSAA were 65.5%, 49.3%, and 20.1%, respectively (P < 0.001). With regard to the response to immunosuppressive therapy, the overall response rate (ORR) in SAA/VSAA treated with rabbit anti-thymocyte globulin with/without cyclosporin A (rATG ± CsA) were significantly superior to those treated with CsA alone, or anabolic steroids (44.4% vs 36.4% and 31.2%, respectively, P < 0.001). The 2-year OS in SAA/VSAA treated with rATG ± CsA, CsA, and anabolic steroids were 54.8%, 54.5%, and 37.6% (P = 0.037), respectively. The incidence of adult AA in Thailand is higher than those in Western countries, and the peak incidence is in the elderly. rATG ± CsA provided a better response than anabolic steroids, translating to the superior survival in SAA/VSAA treated with rATG ± CsA.

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Danazol increases T regulatory cells in patients with aplastic anemia

Abstract: We conclude that Danazol also leads to increase in T-regs in acquired idiopathic AA.

Cited by 12 publications

References 22 publications

The Roles of Sex Hormones in the Course of Atopic Dermatitis

The Roles of Sex Hormones in the Course of Atopic Dermatitis

Aplastic Anemia and Chagas Disease: T. cruzi Parasitemia Monitoring by Quantitative PCR and Preemptive Antiparasitic Therapy

Adult aplastic anemia in Thailand: incidence and treatment outcome from a prospective nationwide population-based study

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