Analysis of the polymorphism of the tumour necrosis factor (TNF) gene and promoter and of circulating TNF-alpha levels in heart-transplant patients suffering or not suffering from severe rejection.

Plasma TNF-alpha levels are generally higher in heart-graft patients who experience a rejection episode than in those who do not. Because the TNF gene and its promoter are polymorphic, we studied the relationships between genetic variability at the TNF locus, the occurrence of graft rejection and TNF-alpha plasma levels in 62 heart-transplant patients in order to investigate inter-individual differences in plasma TNF-alpha levels after allogeneic stimulation. TNF-alpha was immunoenzymatically measured in blood specimens collected on the same day as endomyocardial biopsy. After PCR amplification of DNA, NcoI and AspHI polymorphisms were characterized by their restriction profiles, TNFa microsatellites by electrophoretic separation on acrylamide and the promoter region by sequencing. Plasma levels and molecular genetic results were compared to the grade of heart graft rejection established according to pathological criteria. In our study, allograft rejection was associated neither with NcoI or AspHI polymorphism nor with nucleotide changes in the TNF-A promote. We observed low TNF-alpha levels in n1/n1 homozygous patients and in subjects with G-->A at position--308 of the promoter sequence. Concerning the polymorphism of the TNFa microsatellite, our results might suggest an association with graft rejection but we have to be very careful in drawing conclusions because of the small size of the sample.

Evaluation of plasma levels of tumour necrosis factor alpha and interleukin-6 as rejection markers in a cohort of 142 heart-grafted patients followed by endomyocardial biopsy.

The rejection reaction after cell or organ transplantation has to be detected as early as possible in order to conduct optimal immunosuppressive treatment. Among the numerous events leading to rejection, cytokine production, especially of tumour necrosis factor alpha, is particularly important. Interleukin-6 and tumour necrosis factor alpha were investigated in 142 heart-grafted patients in order to define an early peripheral non-invasive marker of an acute rejection that could fit well with myocardial biopsy results. Cytokines were immunoenzymatically measured in blood specimens collected on the day of the endomyocardial biopsy. The values were compared to the grade of heart graft rejection established according to pathological criteria. Plasma interleukin-6 and especially tumour necrosis factor alpha determined on the day of the rejection diagnosis were significantly increased in the patient sample with moderate or severe rejection when compared with mean values of interleukin-6 and tumour necrosis factor alpha in the patient sample without rejection or with mild rejection (P = 0.04 and 0.001 respectively). Because high levels of tumour necrosis factor alpha may appear before histological signs, this biological marker could be useful in the follow-up of heart-grafted patients.

Plasma cytokines in graft vs host disease and complications following bone marrow transplantation.

A cohort of 201 autologous or allogeneic bone marrow transplanted (BMT) patients were included for studying the evolution of circulating tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) by means of repeated plasma determinations. IL-6 levels were high during major transplant-related complications (TRC) or severe graft vs host disease (GVHD). High levels of TNF-alpha seemed to be associated with chronic GVHD but not with acute GVHD or TRC.

[Cytogenetic course after allograft of bone marrow in chronic myeloid leukemia]. / Evolution cytogénétique après allogreffe de moelle osseuse dans la leucémie myéloïde chronique.

Bone marrow karyotyping was serially performed in 23 Ph1+ chronic myelocytic leukemia patients treated with allogeneic bone marrow transplantation (BMT). Two patients underwent 2 BMT each. Fifteen patients had only normal karyotypes and 8 patients (after 10 BMT) had either sporadic Ph1+ metaphases (6 cases) or cytogenetic signs of relapse (4 cases, of which in 1 case, without hematological symptoms), or both in succession. Sporadic Ph1+ metaphases were found early after BMT (never after the 6th month). Although they were more frequent in non-splenectomized patients than in others, there was no significant correlation between sporadic Ph1+ metaphases and disease features, treatment regimens or evolution after BMT.