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Sexual Differentiation: Immunological Aspects
Published in Gérard Chaouat, The Immunology of the Fetus, 2020
Joyce A. Shelton, Erwin Goldberg
Biochemical isolation and characterization of H-Y would clarify much of the controversy surrounding this antigen; however, progress in this area has been slow. One of the factors responsible is H-Y antigen’s lack of reactivity, which does not favor its isolation by im-munoprecipitative methods. Nevertheless, a number of attempts have been made to isolate H-Y. Hall and colleagues50 reacted antiserum from male-sensitized female C57BL/6 mice with supernatants from Daudi tumor cells, purported to secrete H-Y antigen. Using protein A binding, they isolated an 18,000 mol wt molecule, which they suggest is the H-Y antigen. The report by Bradley and Heslop51 concurs in part with these results. These investigators raised H-Y antisera in rats. These antisera were mixed and used to immunoprecipitate Daudi cell protein that had been pre-reacted with protein A. They identified three protein species that would bind rat anti-H-Y antibodies. One of these proteins was in excess of 200,000 mol wt, the second was in the 50,000 mol wt range, and a third was 20,000 mol wt. They suggest that the smaller protein may be a subunit of the larger or may be the result of different degrees of glycosylation of the same protein. This latter explanation is consistent with reports that H-Y antigen is a glycoprotein.52,53 In these experiments H-Y antigen’s serological reactivity was sensitive to β-galactosidase and galactose oxidase treatments.
Immune Testing in Recurrent Pregnancy Loss*
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
Jeffrey Braverman, Darren Ritsick, Nadera Mansouri-Attia
HY antigen presentation is restricted to a small subset of class I and class II HLA molecules. These HYrHLA alleles include the class II DQB1*05:01, DQB1*05:02, DRB1*15, and DRB3*03:01 alleles. Possession of one or more of these class II HYrHLA alleles allows the maternal immune system to generate an immune response (tolerogenic or effector) to HY antigens present on a male conceptus. These alleles are found at an increased frequency in women suffering secondary recurrent miscarriage following the birth of a son, and the presence of anti-HY antibodies is associated with a high rate of preclinical loss of male embryos, although loss of female embryos is also increased, likely through epitope spreading to additional paternal antigens. The risk for development of anti-HY immunity is increased by the presence of more than 1 class II HYrHLA allele and by the occurrence of complications during the pregnancy with the son [24–26].
Pathology of the Intrahepatic Biliary Tree after Liver Transplantation
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
James Neuberger, Rebecca Harrison
Some help in the understanding of the pathogenesis of chronic rejection may come from knowledge of the risk factors for chronic rejection. Overall, the strongest risk factor for chronic rejection is a previous graft that has developed chronic rejection. In the first allograft, our own study14 suggested that risk factors included a male liver grafted into a female patient; in this scenario, we postulated that there might be an immune reaction against the HY antigen, expressed on the ‘male’ liver; this is analogous to the situation in bone marrow transplantation. Of interest, it has been suggested that the biliary epithelial cells express estrogen receptors and, in vitro at least, blockade of these receptors blocks proliferation and triggers apoptosis of Fas positive biliary epithelial cells.15 The relevance to the in vivo situation is unknown.
Mixed chimerism after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia
Published in Hematology, 2021
Yuling Zhang, Yumiao Li, Liangliang Wu, Ming Zhou, Caixia Wang, Wenjian Mo, Xiaowei Chen, Shilin Xu, Ruiqing Zhou, Shunqing Wang, Yuping Zhang
The impact of allo-HSCT and MC has been found to be associated with the conditioning regimen and donor source [11,20]. The present study suggested that donor/recipient sex-mismatching was a risk factor for MC, especially male donor to female patients in MSD-HSCT. In this study, among the 48 patients in groups 2 and 3, 7 patients were F-F or M-M, accounting for 14.6%, and 30 patients were M-F, accounting for 62.5%, 11 patients were F-M, accounting for 22.9%. Another study also demonstrated that patients with donor/recipient sex-mismatching had a decreased survival and an increased risk of rejection. These may be associated with the h-Y gene on the Y chromosome, and women can develop a rejection reaction against the h-Y antigen [22]. Recent studies have suggested that fludarabine (Flu)-based conditioning regimens are superior to the traditional CTX + ATG regimen in matched donor transplantation [23,24]. Particularly in old patients or patients with a high risk of GF, Flu-based conditioning regimens combined with low-dose cyclophosphamide are more conducive to the survival of patients [2,25]. In the present study, the incidence rate of MC in patients treated with the FCA conditioning regimen was lower than that in patients treated with the CTX + ATG conditioning regimen. The MC rate was high in CTX + ATG-treated patients following transplantation, with an incidence rate of 53.57%. In addition, a high incidence of MC was reported following MSD-HSCT, which may be due to the use of non myeloablative conditioning regimen. This study showed that the incidence of MC in patients receiving BUCY + ATG(h) regimen prior to Haplo-HSCT was low, but the mortality rate was high in MC with SGF, which may be associated with the presence of a donor-specific antibody in the recipient when HLA is incompatible [14,26].
Methoxychlor metabolite HPTE alters viability and differentiation of embryonic thymocytes from C57BL/6 mice
Published in Journal of Immunotoxicology, 2018
Lucie Leung-Gurung, Priscilla Escalante Cobb, Faraj Mourad, Cristina Zambrano, Zachary Muscato, Victoria Sanchez, Kanya Godde, Christine Broussard
Only one other published study (Brown et al. 2006a) has directly investigated whether an EDC might alter thymocyte developmental programing. Those authors treated six-week-old H–Y-specific TCR transgenic mice with DES twice by subcutaneous injection. A presence of the H–Y TCR transgene allowed a large proportion of thymocytes to be signaled for differentiation simultaneously and ultimately give rise to CD8 T-cells. In female mice (where H–Y antigen is absent) expression of the transgene results in a preponderance of CD8 SP cells, whereas in males (H–Y antigen present) the CD8 SP are mostly absent. In DES-treated H–Y TCR transgenic mice, the ratio of CD8 SP to other cells changed, but the absolute numbers of cells remained the same (calculated from reported data) in females (control ∼28 × 106 vs. DES ∼21 × 106) and in males (control ∼4.3 × 106 vs. DES ∼4.0 × 106). These data suggested that in H–Y TCR transgenic mice, preexisting CD8 SP were resistant to treatment with - or that differentiation of DP thymocytes into CD8 SP was unaffected by – DES treatment. However, DP thymocyte cell numbers were reduced in females (control ∼200 × 106 vs. DES ∼97 × 106) as well as in males (control ∼15 × 106 vs. DES ∼0.1 × 106). Reductions in DN (by 16% of control cell numbers) and CD4 SP (by 92% of control) were only seen in DES-treated males. From the data, one can conclude thymocytes strongly stimulated through the TCR (H–Y males, antigen present) experienced broader losses of populations than thymocytes (H–Y females, no antigen) that were not. If strongly stimulated thymocytes were depleted by DES, one might expect a reduction in the proportion of TCRhigh cells three days after injection. Their results show, however, enrichment for TCRhigh cells instead of any reduction. These data contrast with the present findings of a preferential loss of TCRhigh thymocytes.