Serum matrix metalloproteinase-3 levels monitor the therapeutic efficacy in Syrian patients with rheumatoid arthritis.

Background: The plans for the successful treatment of rheumatoid arthritis (RA) seek to attain low disease activity or reach clinical remission. Objective: Our study aimed to compare the serum MMP-3 levels with predictors of response to therapy of rheumatoid arthritis in Syrian patients and explore its worth as a new valuable biomarker for RA therapy outcomes in daily practice. Methods: Serum samples were gathered from 43 RA patients at diagnosis and 12 weeks of therapy. Related clinical and laboratory tests were estimated, levels of serum MMP-3 were measured by ELISA method and the disease activity was assessed using disease activity scores in 28 joints with an erythrocyte sedimentation rate (DAS28-ESR) before and after therapy. Results: The mean of Serum MMP-3 levels significantly decreased (322.3 ± 43.83 ng/ml) after therapy (12 weeks) in RA patients compared to its mean at baseline (486.49 ± 34.5 ng/ml). There wasn't a statistically significant difference in the mean of MMP-3 levels before and after therapy (P = 0.137) in non-responder patients. Patients who showed a good response (N = 38) presented higher MMP-3 levels at first which subsequently decreased significantly at the 12-week follow-up (P < 0.05). Also, there was a statistically significant difference in MMP-3 levels between the two groups of patients after therapy (P = 0.002). To differentiate between RA patients who responded to therapy and who did not, our results found that the cut-off value of serum MMP-3 was 317.8 ng/ml (sensitivity was 80%, specificity was 73%, AUC was 0.818, 95% CI: 1.114-112.5; P = 0.045) and the best cut-off value of DAS28-ESR was 5.325 (sensitivity 100%, specificity 100%, AUC = 100%,95% CI: 15.2 to 47203.8). Conclusion: serum MMP-3 can be added as a novel and valuable biomarker in estimating the therapeutic response in RA patients, but it isn't better than DAS28-ESR.

The association of serum RANKL levels with disease activity and hematological parameters in Syrian patients with rheumatoid arthritis.

Our study aims to detect whether the serum RANKL could be a novel potential biomarker for activity and diagnosis of rheumatoid arthritis (RA). It included fifty-eight of RA patients and thirty of equal age and sex matched controls. Disease activity was determined by using DAS28-ESR. Serum Levels of RANKL were assayed by ELISA and compared with parameters such as ESR, CRP, Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). The serum RANKL levels were higher in RA patients compared to controls. There was an increase in its levels mean among post-menopausal patients compared to post-menopausal healthy group. RANKL levels were also higher in ACPA positive patients than ACPA negative. Our study found a correlation between RANKL levels and some parameters: DAS28, ACPA, CRP, and symptom duration. There was a moderate inverse correlation between RANKL levels and BMD. By ROC curve, our results displayed that the best cut-off value of RANKL was 178.99 pg/ml (sensitivity 79.31%; specificity 90%) to differentiate between RA patients and controls. In conclusion, elevated serum RANKL can be used as an indicator of disease activity and a diagnostic new biomarker in patients with early RA.

Two Novel Mutations of the NPM1 Gene in Syrian Adult Patients with Acute Myeloid Leukemia and Normal Karyotype.

OBJECTIVE: Somatic mutations in exon 12 of the NPM1 gene is one of the most common genetic abnormalities in adult acute myeloid leukemia (AML), which is observed in 25-35% of AML patients and in 50-60% of patients with cytogenetically normal AML (CN-AML). METHODS: We performed Sanger sequencing of exon 12 of the NPM1 gene, on 44 CN-AML patients to characterize NPM1 status. RESULTS: In this study, NPM1 mutations were identified in 10 (22.7%) of the 44 CN-AML patients. Among the 10 patients with NPM1 mutations, type A NPM1 mutations were identified in 8 (80%) patients, whereas non-A type NPM1 mutations were observed in 2 (20%) patients. Two non-A type NPM1 mutations were not previously reported: c.867-868InsCGGA and c.861-862InsTGCA. These two novel mutant proteins display a nuclear export signal (NES) motif (L-xxx-L-xx-V-x-L) less frequently and L-x-Lx-V-xx-V-x-L it has been never seen before, yet. However, both novel mutations show a tryptophan loss at codon 288 and 290 at the mutant C-terminus which are crucial for aberrant nuclear export of NPM into the cytoplasm. CONCLUSIONS: This study suggests previously unreported NPM1 mutations may be non-rare and thus additional sequence analysis is needed along with conventional targeted mutational analysis to detect non type-A NPM1 mutations.

De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report.

BACKGROUND: Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. CASE PRESENTATION: Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. CONCLUSIONS: To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.

A novel frameshift mutation in FGA (c.1846 del A) leading to congenital afibrinogenemia in a consanguineous Syrian family.

Congenital afibrinogenemia is a rare autosomal recessive coagulation disorder characterized essentially by bleeding symptoms, but miscarriages and, paradoxically, thromboembolic events can also occur. Most reported mutations leading to congenital afibrinogenemia are located in FGA encoding the fibrinogen A α-chain. In this study, we analysed 12 individuals from a consanguineous Syrian family with reduced or absent fibrinogen levels: those with fibrinogen levels around 1 g/l (n = 7) were found to be heterozygous for a novel frameshift mutation in FGA exon 5 (c.1846 del A) and those with undetectable fibrinogen levels (n = 5) were homozygous for the same mutation. This novel frameshift mutation is the most C-terminal causative FGA mutation identified to date in afibrinogenemic patients. The resulting aberrant Aα-chain (p.Thr616HisfsX32) is most likely synthesized, but is less efficiently assembled and/or secreted into the circulation given the phenotype of asymptomatic hypofibrinogenemia in heterozygous individuals and bleeding diathesis in homozygous individuals.

Diagnostic performances of anti-cyclic citrullinated peptide antibodies type IgM, IgA and IgG in Syrian patients with rheumatoid arthritis.

BACKGROUND: To determine the diagnostic performances of anti-cyclic citrullinated peptide antibodies (anti-CCP) type IgM, IgA and IgG and rheumatoid factor (RF) in Syrian patients with rheumatoid arthritis. METHODS: 64 patients with rheumatoid arthritis were included in our study. Anti-CCP IgM, IgA and IgG and rheumatoid factor (RF) were detected using ELISA. Blood samples were collected from patients with definite rheumatoid arthritis according to (ACR) criteria in Al Mwasaa University Hospital and Al Assad University Hospital, Damascus, Syria, from December 2007 to December 2008. RESULTS: The sensitivity of anti-CCP IgG was 71.9% and specificity was 100%, Whereas the sensitivity of anti-CCP IgM was 70.3% and specificity was 64%, the sensitivity of anti-CCP IgA was 43.75% and specificity was 100%, RF IgM showed a sensitivity of 70.3% and a specificity of 96%, and anti-CCP IgG prevalence in patients with negative RF was 31.6%. All tests showed no correlation with gender in RA patients. CONCLUSIONS: This study demonstrates that anti-CCP IgG is a highly specific marker for RA and has diagnostic value especially in RF negative patients.