ABSTRACT
Megakaryopoiesis requires a highly complex series of cellular events in which a hematopoietic stem cell generates a cascade of committed progenitors and culminates with the production of circulating blood platelets. Megakaryopoiesis is regulated by several factors and cytokines that affect the proliferation and differentiation of megakaryopoietic cells. The aim of this study was to evaluate the role of some cytokines namely Thrombopoietin [TPO], Transforming growth factor [TGF-beta1] and lnterleukin 6 [IL-6] in regulation of megakaryopoiesis in various platelet disorders. This study was conducted on 72 patients with various platelet disorders; they were either thrombocytopenic [ITP "group I" or liver cirrhosis [LC] "group II" patients] or they presented with reactive thrombocytosis "group III". [According to modified Child classification group II patients was divided into three subgroups; Child A, Child B and Child C]. Twelve apparently healthy volunteers were included in the study for comparison. Estimations of serum TPO level, TGF-beta1 level and IL-6 level by ELISA technique were done for all studied groups. A highly significant increase in TPO and significant increase in IL-6 levels was noted in ITP group compared with the control group while TGF-beta1 was non significantly increased. In LC group and subgroups [Child A] a significant increase in TPO was noted on comparing with the control group but non significant increase in Child B and C; with progressive decrease of TPO level from Child A to Child B and Child C respectively. In LC group and Child C and B the TGF-beta1 was highly significantly increased on comparing with control group. Also it was significant increased in Child A when compared with control group i.e. there was progressive increase in TGF-beta1 with the progression of liver damage. A significant reduction in IL-6 was noted in LC group on comparing with the control group. A non significant reduction in IL-6 was noted in Child A, B and C group on comparing to the control group. In thrombocytosis group a significant increase in TPO, TGF-beta1 and IL-6 levels were noted compared to the control group. Estimation of serum TPO in ITP, liver cirrhosis and reactive thrombocytosis seems to be of benefit in diagnosis and evaluation of megakaryopoiesis state in these platelet disorders. Also estimation of TGF- beta1 can be used as good indicator of liver disease progress. TGF-beta1 was increased in thrombocytosis and this makes highlight to its role in feed back inhibition of megakaryopoiesis. Serum IL-6 was significantly increased in reactive thrombocytosis and this may confirm its role in stimulation of megakaryopoiesis
Subject(s)
Humans , Male , Female , Thrombopoietin/blood , Transforming Growth Factor beta/blood , Interleukin-6/blood , Liver Cirrhosis , Thrombocytosis , Purpura, ThrombocytopenicABSTRACT
Outcome of unrelated donor marrow transplantation is influenced by donor/recipient matching for HLA. Prior studies assessing the effect of mismatch at specific HLA loci have yielded conflicting results. Disparity for HLA-A or HLA-B antigens increases the risk of poor marrow graft outcome, but little is known about the relevance of HLA-C matching. This work aimed to evaluate the effect of HLA-C matching on hematopoietic stem cell transplant, outcome specifically on the acute graft versus host disease [aGVHD]. Seventy patients given hematopoietic stem cell transplant [HSCT] in different transplant centers with their relevant donors were included in the study, HLA class I [HLA-A, -B] and class II [DRB1, DQR1, DPB1] typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe [PCR-SSOP] and HLA-C typed by PCR-sequence specific priming [PCR-SSP] technique. The risk of aGVHD during the first three months after HSCT was estimated. Fifty two [74.3%] donor/recipient pairs were mismatched for HLA class I alleles, eighteen [34.6%] of them experienced aGVHD. While no history ofaGVHD was reported in eighteen HLA class I full matched pairs [25.7%]. Higher incidence of aGVHD was observed with isolated HLA-A mismatch [28.6%], and for isolated HLA-B and HLA-C locus mismatch, the incidence were 25% and 16.7% respectively. The incidence of aGVHD was elevated if HLA-A or HLA-B mismatch is associated with HLA-C mismatch [40% and 37.5% respectively]. Much higher incidence of aGVHD was associated with combined HLA-A-B and-C mismatch [44.4%]. The estimated odds ratio [OR] of aGVHD for total HLA-C mismatch relative to matched pairs [univariable model] was 5.0 [95% CI 1.3-19.4; P= 0.01]. The degree of HLA-C allele mismatch [one or two alleys mismatch] were significantly related to aGVHD outcome [OR, 3.9, P= 0.03; OR, 10.8; P .009 respectively]. HLA-A or HLA-B allele disparity was also associated with aGVHD. As regard the analysis of total HLA-A and -B mismatched pairs with their corresponding matched locus, they demonstrated significant adverse effect on aGVHD [OR, 2.8; P=0.04; OR 3.0; P=0.03]. It was concluded that HLA-C may function as a powerful transplantation antigen. HLA-C compatibility should be incorporated into algorithms for donor selection to improve the outcome especially in patients who have an increased risk. The presence of HLA-C mismatch with either HLA-A or HIA-B mismatch leads to a synergistic increase in cytotoxic responses and poor graft outcomes [the development of aGVHD]; however, isolated HLA-C mismatch may be acceptable with respect to T-cell mediated alloreactivity