Human chorionic gonadotropin and indolamine 2,3-dioxygenase in patients with GVHD

Abstract

GVHD is a major complication following allogeneic hematopoietic SCT, and is associated with substantial morbidity and mortality. Based on the results of our previous clinical study with females treated with human chorionic gonadotropin (hCG) as preconditioning therapy for in vitro fertilization, we hypothesized that low-dose hCG stimulates indoleamine-2,3-dioxygenase (IDO), IL 10 and regulatory T cells (Treg), thereby suppressing clinical manifestations of chronic GVHD. Active chronic GVHD localized at skin, subcutaneous tissue, joints orgastrointestinal tract that was refractory or intolerant to glucocorticoid therapy improved substantially in 12 of 20 patients treated with hCG for 8 weeks (off-label), enabling a glucocorticoid dose reduction of 28% (average). Twelve of 19 patients with chronic GVHD of the skin responded to hCG therapy with a reduction of 25% (average) in their total skin score. HCG treatment increased IDO expression at median by sevenfold in peripheral mononuclear cells and IL10 levels in serum up to twofold at median from the pretreatment baseline. Further, an expansion of the Treg cell population was measured in one patient, which is also associated with the induction of tolerance. This novel application of low-dose hCG was well tolerated and is of clinical interest for GVHD treatment.

Correlation Between Immunological Laboratory Status of Omega-3-Fatty-Acid-Supplemented Patients of a German Fertility Centre and Outcome of IVF-Treatment

“…On the other hand we found increased numbers of regulatory T-cells in successfully IVFtreated patients, concordant with literature: increased concentrations of hemeoxygenase-1 lead to an increase in regulatory T-cells and therefore to a promotion of fertilization, implantation and fetal growth [45]. Stimulation by human chorionic gonadotropin increases numbers of regulatory T-cells and leads to increased IVF-success-rates [46]. Increased numbers of regulatory T-cells are unequivocally related with increased IVF-success [47].…”

Neurological and Inflammatory Manifestations in Sjögren’s Syndrome: The Role of the Kynurenine Metabolic Pathway

“…Twelve of 20 GVHD individuals, who were non-responders to corticosteroids, presented clinical improvement in skin inflammation with human chorionic gonadotropin (hCG) treatment [251]. They also showed a significant increase in IDO mRNA expression in PBMCs and in IL-10 expression in the blood serum [251].…”

“…Twelve of 20 GVHD individuals, who were non-responders to corticosteroids, presented clinical improvement in skin inflammation with human chorionic gonadotropin (hCG) treatment [251]. They also showed a significant increase in IDO mRNA expression in PBMCs and in IL-10 expression in the blood serum [251]. The underlying mechanism of action was thought to occur via stimulation of IDO-mediated immunotolerance, similar to the mother/fetus coexistence [144].…”

Recent advances on cellular therapies and immune modulators for graft-versus-host disease

“…A recent report has also described a clinical benefit related to the administration of low-dose human chorionic gonadotropin (hCG) to patients with severe or moderate chronic GVHD [107]. Twelve of the 20 treated patients had an objective partial response during 8 weeks of daily subcutaneous treatment with 187.5 IU of hCG.…”

“…Phase I-II [94,95] Low-dose hCG MSD Myeloablative Phase I [107] TCR-ab/ CD19 depletion HLA-haploidentical Myeloablative Phase I/II [110] CD3/CD19 depletion HLA-haploidentical; MMFD FLU † , TT, melphalan, OKT3 or ATG Phase II [108,109] CD45RA depletion N.A. N.A.…”