ABSTRACT
Background: allogeneic hematopoietic stem cell transplantation [HSCT] is widely used to treat various hematological malignant and non-malignant diseases. The occurrence of complications following HSCTas graft versus host disease[GVHD], hepatic veno-occlusive disease [VOD], oral mucositis [OM], drug induced hepatic and renal adverse events- is highly variable and dependent on a multitude of host, donor, and treatment factors. Identifying important genetic variables will allow for better prediction of HSCTrelated outcomes, and in the process of identifiing these susceptibilities, that could help to develop targeted interventions
Objectives: to evaluate impact of the C677T polymorphism of 5,10-methylenetetrahydrofolate reductase [MTNFR] on the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation as acute gruff versus host disease [GVHD],oral mucositis ,drug induced hepatic and renal toxicity, transplant related mortality[TRM] and overall survival[OS]
Patients and Methods: we examined the association of a single nucleotide polymorphism [SNP] at position 677 in the MTHFR gene of patients with outcomes of allogeneic HSCT. MTHFR genotyping was performed by po2ymerase chain reaction-restriction fiagment length polymorphism [PCR-RFLP]
Results: 46 Patients with complete clinical records were recruited. Median age at the time of HSCT was 22 years [range 3-42 years]; 32 patients [69.6%] above >/=18 years, and the median follow-up period of survivors was 21 months. 212efrequencies of the MTHFR C677T genotypes in patients were 43.5% [20 patients] for 677CC, 50% [23 patients] for 677CX and 6.5% [3 patients] for 677TT; the allelic frequency of the 677T was 31.5%. Recipient MTHFR677 in CT or TT versus CC showed non-statistically significant higher incidence of acute GVHD [7/26] 26.9% versus [2/20] 10%; p=0.15, hepatic toxicity [11/26] 42.3% versus [5/20] 25%, p= 0.22 and TRM [5/26] 19.2% versus [2/20] 10%; p=0.45. Recipients with variant allele MTHFR 677T were associated with lower non statistically signijicant overall survival; p=0.281. Conclusion: Genofyping for WHFR C677T before HSCT could have clinical significance, not statistically proven in our study, in prediction of patients at high risk of developing poor outcomes. Larger studies with homogeneous HSCT cohort are needed to identifi such potential phar]nacogenetic markers with suflciently strong evidence to be used in clinical practice
ABSTRACT
Activin is a growth and differentiation factor of many cell types and has recently been implanted in inflammatory processes. Clinical data demonstrating roles of activin and its antagonist inhibin in inflammatory arthropathies, are lacking. The Study is to measure serum and synovial fluid levels of activin A and inhibin A in patients with rheumatoid arthritis [RA] systemic lupus erythematosus [SLE] and osteoarthritis [OA] and correlate them with disease activity parameters. This study included 60 patients with three rheumatic diseases [20 with RA, 20 with SLE and 20 with OA], as well as ten healthy subjects as a control group. All of them were subjected to complete history, physical and musculoskeletal examination and estimation of disease activity index [DAS- 28] for RA and [SLEDAI] for SLE. The following investigations were done for all subjects; serum and synovial activin A and inhibin A; in addition to complete blood picture, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP],rheumatoid factor [RF], antinuclear antibodies [ANA],anti-dsDNA, serum complement [C 3, 4] and Xrays on affected joints. The mean values of serum activin A were significantly higher in RA, SLE and OA than controls [P<0.001] also in RA and SLE versus OA [P<0.05 for both]. The mean values of serum inhibin A were significantly higher in all studied groups than controls [P<0.05 for RA and OA and P<0.001 for SLE]. Also serum inhibin levels were significantly higher in SLE versus OA P<0.001, but there was no significant differences between RA and SLE. Synovial fluid activin and inhibin A were significantly higher in RA than OA [P<0.05 for both]. Positive correlations were found between serum activin A and disease activity parameters of RA morning stiffness [MS], Ritchie index [RI], ESR, CRP and DAS 28] P<0.05, for all. Also positive correlation was found between serum inhibin A and RI in RA patient [P<0.05]. In SLE, positive correlations were found between serum activin A and inhibin A with ESR [P<0.001 for activin and P<0.05 for inhibin A and SLEDAI [P<0.001 for both activin and inhibin]. No correlation were found between synovial activin and disease activity and negative correlation between synovial inhibin and ESR. The significant increase of serum and synovial activin A and inhibin A in RA and SLE and their positive correlations with disease activity parameters of RA and SLE suggest pro-inflammatory action. However the lack of correlations or negative correlation of their synovial levels with disease activity may indicate their anti inflammatory action, We recommended further studies to detect the exact role of activin A and inhibin A