Imbalance in serum soluble CD30/CD30L and CD40/CD40L systems are associated with ovarian tumors

The aim of the study was to examine the concentrations of the soluble receptors and their ligands of CD30/CD30L and CD40/CD40L systems in the serum of women with ovarian tumor and in the ovarian cyst fluid of women with Cystadenoma serosum. The study included 120 women with ovarian tumors. As a control, sera were obtained from 60 healthy female volunteers. Concentrations of the sCD30, sCD30L, sCD40 and sCD40L in the serum and the ovarian cyst fluid were measured by ELISA enzyme-linked immunosorbent assay. Concentrations of both sCD30 and sCD30L in serum of women with ovarian tumors were significantly higher than in control (p < 0.0001). The highest serum receptor and its ligand levels were observed in women with ovarian cancer (p < 0.0001). Moreover, results showed significantly increased levels of sCD40 and sCD40L serum in women with ovarian tumors, as compared to the control group (p < 0.0001). The highest concentration of sCD40 in the serum of women with ovarian cancer and sCD40L in serum of women with Teratoma maturum (p < 0.0001) were observed. Impaired apoptosis among women with ovarian tumors is associated with the impairments of soluble CD30/CD30L and CD40/CD40L systems. Measurement of studied parameter concentrations in serum of women with ovarian tumors has been suggested to be a potential tool in monitoring of inflammatory. Evaluation of sCD30, sCD30L and sCD40 might be an early diagnostic marker in patients with the ovarian cancer. Concentrations of the studied parameters in the ovarian cyst fluid higher than the serum values suggest local suppression of the immune response. However, the final evaluation of the importance of measurement of serum levels of them requires further investigation.     

Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p<0.004). Patients carrying the DR2 alleles, DRB1*1501,*1502 or*1601 were at a lower risk of producing anti-donor HLA antibodies.     

Implication of soluble and membrane HLA class I and serum IL-10 in liver graft acceptance.

Membrane HLA class-I expression (mHLA-I), soluble HLA class-I antigens (sHLA-I) and interleukin (IL)-10 are different factors implicated in the special acceptance of liver allograft. In this study, pre- and post-operative levels of mHLA-I in peripheral blood lymphocytes (PBL) and serum sHLA-I were analyzed in 86 liver transplants, immunosuppressed with Cyclosporine-A, methylprednisolone and azathioprine, and classified into acute-rejection (AR, n = 28) and non-acute-rejection (NAR, n = 58) groups. Serum IL-10 was studied in 47 recipients (AR-group, n = 16 and NAR-group, n = 31). Pre-transplant values of mHLA-I and sHLA-I showed a bimodal distribution (high/low) in NAR-recipients, but in AR-patients were mainly included in the low expression/secretion zone (mHLA-I, p < 0.02 and sHLA-I, p < 0.05). Consequently, average pre-transplant mHLA-I (868 +/- 109 versus 998 +/- 123, p < 0.05) and sHLA-I (1.3 +/- 0.4 versus 2.02 +/- 0.7 microg/ml, p < 0.01) was lower in the AR- than in the NAR-group. After transplant both parameters decreased in the NAR-group, but increased in AR-recipients previous to and on rejection diagnosis day. Additionally, serum IL-10 levels were significantly higher (p < 0.01) in the NAR than in the AR-group during the first 24 h post-transplant. In conclusion, low pre-transplant mHLA-I and sHLA-I levels pre-dispose liver recipients to acute rejection, whereas early post-transplant increases of serum IL-10 appear to be related to a good liver allograft acceptance.     

Soluble CD30 binds to CD153 with high affinity and blocks transmembrane signaling by CD30.

CD30 is an unusual member of the TNF receptor superfamily with a duplicated segment within its extracellular domain that may function as an additional ligand binding site. The extracellular domain of CD30 is shed from cells and soluble CD30 levels are elevated in certain disease states. Soluble CD30 may bind to its ligand, CD153, with high affinity and block its interaction with membrane-bound CD30. We have generated soluble recombinant forms of CD30 and CD153 in order to characterize their interaction and assess their biological activity. Soluble trimeric CD153 bound to membrane-anchored CD30 with a relatively high affinity (K(D)=23 nM) and was effective in triggering cell death and TNF-alpha production in the presence of cross-linking antibodies. The affinity and kinetics of the interaction between soluble CD30 and CD153 were determined using the BIAcore biosensor. In contrast to other members of the TNF receptor superfamily, soluble monomeric CD30 bound to its ligand with high affinity (K(D)=4.5 nM) and prevented the interaction of cellular CD153 with immobilized CD30. Furthermore, soluble CD30 blocked cell death signals generated by cell surface-expressed CD30 effectively. These data suggest that soluble CD30 may have biological functions in vivo.     

Non-donor specific anti-human leukocyte antigen (HLA) antibodies are not associated with poor outcome in hematopoietic stem cell transplant recipients

Testing for anti-human leukocyte antigen (HLA) antibodies has now become standard practice in allogeneic hematopoietic stem cell transplantation (HSCT), and anti-HLA antibodies (both donor specific and non-donor specific) are being identified and have many potential consequences. Most studies suggest that donor-specific HLA antibodies lead to adverse outcomes, though little is reported on non-donor specific anti-HLA antibodies. We present the results of a retrospective cohort analysis of 157 patients who received HSCT at the University of Rochester over a period of four years. We identified 45 patients (28.7%) who had detectable anti-HLA antibodies, while only one patient (0.6%) had donor-specific anti-HLA antibodies. Patients with prior pregnancies and multiple transfusions were at increased risk to develop antibodies. In our cohort, the presence of non-donor specific anti-HLA antibodies did not significantly impact overall survival, progression free survival, graft failure, or transplant-related mortality.     

Shared cadaver donor-husband HLA class I mismatches as a risk factor for renal graft rejection in previously pregnant women

During the last few years, we have observed four cases in which accelerated rejection of a cadaver donor kidney in a previously pregnant woman could be clearly attributed to the rapid emergence of anti-human leukocyte antigen (HLA) antibodies that had been stimulated by mismatched paternal antigens but were completely undetectable at the time of transplantation. In addition to reviewing those cases, we also reviewed data on 19 other women with a history of at least one pregnancy who underwent transplantation with a first cadaveric kidney since 1991 and were followed for at least six months. The HLA antigens of the husbands had to have been determined and all accelerated rejection or early graft losses due to confirmed or presumed immunological causes were considered. Of the 19 additional women meeting these inclusion criteria, three suffered early immunological graft loss. As in our index cases, two of these women had also received kidneys from donors who shared at least one major immunogenic mismatched antigen with the respective husband for a total of six of seven women with early immunological graft loss. Only one of the 16 women without accelerated rejection or early immunological graft loss had a donor who shared a mismatched antigen with her husband. The difference between the two groups is statistically significant (p = 0.0005). These findings, considered with individual cases reported by other groups, indicate that transplantation from a cadaver donor with immunogenic mismatched class I HLA antigen(s) shared with the husband should be avoided in women with a previous history of pregnancy even when anti-HLA antibodies are not currently detected.     

CD30 cell expression and abnormal soluble CD30 serum accumulation in Omenn's syndrome: Evidence for a T helper 2-mediated condition

Omenn's syndrome (OS) is a severe immunodeficiency, characterized by clinical and laboratory features reminiscent of a T helper type-2 (Th2) response. CD30, a member of the tumor necrosis factor receptor superfamily, has been found to be preferentially expressed by human T cell clones exhibiting a Th2-like profile and function. We investigated whether there are derangement in CD30 expression in tissues, and/or abnormalities in soluble CD30 (sCD30) levels in the serum, or both, of three children with OS and one child with maternal engraftment and Omenn's-like syndrome (OLS). Large proportions of tissue-infiltrating T lymphocytes from all four patients expressed CD30, whereas in control tissues, including peripheral blood, CD30⁺ T lymphocytes were extremely few or absent. In addition, levels of sCD30 were abnormally increased in all patients' sera. T cell clones were generated from sorted CD30⁺ and CD30^? peripheral blood T cells of the patient with OLS who showed unusually high numbers of circulating CD30⁺ T lymphocytes. Most CD4⁺ T cell clones derived from CD30⁺ cells showed a Th2-like cytokine profile, whereas the majority of clones generated from CD30^? T cells were Th1. These findings support the hypothesis that Th2 cells are involved in the pathogenesis of OS. Moreover, they provide evidence that detection of CD30⁺ T cells in tissues, increased levels of sCD30 in biological fluids, or both, reflect the presence of immune responses characterized by prevalent activation of T cells producing Th2 cytokines.     

Serum antibodies to HIV-1 are produced post-measles virus infection: evidence for cross-reactivity with HLA

Convalescent sera obtained from patients who were recently recovered from an acute measles virus infection were tested for the presence of anti-HIV-1 antibodies by Western blot analysis. While 16% (17/104) of control sera displayed reactive bands to a variety of HIV proteins, 62% (45/73) of convalescent sera demonstrated immunoreactive bands corresponding to HIV-1 Pol and Gag, but not Env antigens. This cross-reactivity appears to be the result of an active measles infection. No HIV-1 immunoblot reactivity (0/10) was observed in sera obtained from young adults several weeks after a combined measles, mumps, and rubella (MMR) vaccination. Interestingly, examination of anti-HLA typing sera specific for either class I and class II molecules revealed that 46% (19/41) of these sera contained cross-reactive antibodies to HIV-1 proteins. Absorption of measles sera with mixed lymphocyte reaction (MLR)-activated lymphocytes and/or HIV-1 recombinant proteins significantly decreased or removed the presence of these HIV-1-immunoreactive antibodies. Together, these findings suggest that the immune response to a natural measles virus infection results in the production of antibodies to HIV-1 and possibly autoantigens.     

HLA mismatching and cytomegalovirus infection as risk factors for transplant failure in cyclosporin-treated renal allograft recipients

In a study of the effects on renal allograft survival of HLA mismatching, mismatching for cytomegalovirus (CMV) antibody status, and post-transplant CMV infection, 148 cyclosporin-treated renal transplant recipients were given kidneys optimally matched for HLA-A, -B, and -DR antigens but not matched for CMV antibody status. Mismatching for HLA-B and -DR antigens was associated with a greater number of rejection episodes and a lower graft survival, but mismatching for CMV antibody status and posttransplant primary or recurrent CMV infection exerted no effect on graft survival. The role of matching of renal transplant recipients and donors for CMV antibody status in preference to HLA matching (proposed as a means of reducing the mortality associated with primary CMV infection) is discussed.