Red Cell Alloimmunization in Repeatedly Transfused Sudanese Patients with leukemia in Northern Sudan.

BACKGROUND: Leukemia frequently causes anemia; thus patients need products containing normal blood or RBCs for treatment. Anti-red blood cell alloantibody formation is still a critical challenge in transfusion. OBJECTIVES: The current study aimed to investigate RBC alloantibodies in Sudanese leukemia patients who receive multiple blood transfusions at the cancer center in Dongola and Maroyee, Northern Sudan. MATERIALS AND METHODS: At the Northern State oncology center in Dongola and Maroyee, Sudan, an across-sectional descriptive study design was used. In this study, 100 leukemic patients who had received blood transfusions three times or more were enrolled. From each participant, Peripheral blood was drawn in amounts of 3 ml in EDTA vacutainer tubes for ABO blood group and Rh factor testing and 3 ml in non-additive containers for antibody screening and Alloantibody identification. All individuals' ABO blood groups and Rh factors were determined using the slide method. Indirect Coombs test apply to detect alloantibodies by Polly Specific antihuman globulin reagents using tube method techniques. Alloantibody identification was performed by DiaMed-ID microtyping system. RESULTS: Incidence of alloimmunization was 11%, with 11 alloantibodies found in 11 patients. The most common alloantibody was kell (36.4%), followed by Lea (27.2%; 3/11), then P (18.2%; 2/11) and M (18.2%; 2/11). CONCLUSION: Anti kell antibody was the most prevalent alloantibody among leukemic patients with multiple transfusions.

TNF-α-308A allele Carrier Induced to Development of Chronic Lymphocytic Leukemia in Sudanese Population at Earlier Age.

BACKGROUND: several studies have been performed to investigate the association of TNF-α-308G>ASNP and CLL susceptibility However, the results are inconsistent. This study aimed to investigate the association between TNF-α-308G>ASNP of the TNF-α gene and CLL risk in the Sudanese population and correlated genotypes with clinicopathological features. METHODS: A case-control study was conducted in Khartoum state, during the period from April 2017 to April 2018, involved 110 CLL patients and 50 healthy volunteers. Physical examination, Complete Blood Count, and immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as Rai and Binet were studied. CD38 and ZAP70 were performed by Flow Cytometry. Blood samples were collected from all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit and analyzed TNF-α-308G>ASNP by using AS-PCR. The statistical analysis was performed using SPSS. RESULTS: TNF-α-308G>A genotype frequencies were GG (10.0%), GA (87.3%), and AA (2.7%) among the CLL patients, and GG (14.0%), GA (80.0%), and AA (6.0%) in the control group. The comparison of CLL patients with the control group did not show any statistically significant relationship for the genotypic and allelic frequencies. Furthermore, no association was observed between the TNF-α-308G>ASNP and gender, hematological parameters, clinical stages systems, CD38 expression, and ZAP-70 expression. The presence of theTNF-α-308Aallele was associated with a lower mean age. CONCLUSIONS: These results indicate that TNF-α-308G>A genotypes are not involved in the predisposition to the development of CLL. TNF-α-308A allele carrier induced to development of CLL at an earlier age.

The SARS-CoV-2 Antibodies, Their Diagnostic Utility, and Their Potential for Vaccine Development.

Antibodies (Abs) are important immune mediators and powerful diagnostic markers in a wide range of infectious diseases. Understanding the humoral immunity or the development of effective antibodies against SARS-CoV-2 is a prerequisite for limiting disease burden in the community and aids in the development of new diagnostic, therapeutic, and vaccination options. Accordingly, the role of antiviral antibodies in the resistance to and diagnosis of SARS-CoV-2 infection was explored. Antibody testing showed the potential in adding important diagnostic value to the routine diagnosis and clinical management of COVID-19. They could also play a critical role in COVID-19 surveillance, allowing for a better understanding of the full scope of the disease. The development of several vaccines and the success of passive immunotherapy suggest that anti-SARS-CoV-2 antibodies have the potential to be used in the treatment and prevention of SARS-CoV-2 infection. In this review, we highlight the role of antibodies in the diagnosis of SARS-CoV-2 infection and provide an update on their protective roles in controlling SARS-CoV-2 infection as well as vaccine development.

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism.

Purpose: Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL. Patients and Methods: This case-control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using ß-globin gene as an internal positive control. Results: The genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = <0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42-29.74, P < 0.001). Conclusion: Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.

Assessment of risk factors for deep vein thrombosis associated with natural anticoagulants and fibrinolytic regulatory proteins.

Deep vein thrombosis (DVT) is a critical condition and a potential cause of mortality and morbidity in Africa and worldwide with a high recurrence rate. The study was designed to assess the roles of natural anticoagulants and fibrinolytic regulatory factors in the development of DVT in Sudanese patients. A case-control study was conducted in Omdurman Teaching Hospital, Khartoum State over a period of 1 year. The study enrolled 200 patients diagnosed with DVT and 200 age-matched and gender-matched controls. Demographic data and data on acquired risk factors were collected using a semi-structured questionnaire. Protein C (PC), protein S (PS), antithrombin III (AT-III), thrombin-activable fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor-1 (PAI-1) were measured in patients and controls. Among the patients with DVT, 5.5% had PC deficiency, 8.5% had PS deficiency, and 3% had AT-III deficiency. Elevated TAFI and PAI-1 levels were demonstrated in 1.5 and 0.5% of patients, respectively. Risk factors for DVT (overweight, surgical history, and family history of DVT) were remarkably higher in patients than in controls. Among the female participants, pregnancy and usage of oral contraceptive pills were the highest associated risk factors for DVT. The findings concluded that the early assessment of risk factors, including the measurements of natural inhibitors, can predict the occurrence of DVT before it is actually detected in patients.

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia.

PURPOSE: Glutathione S-transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML. PATIENTS AND METHODS: This case-control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers. RESULTS: GSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys. CONCLUSION: In conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.

Molecular epidemiology of malaria parasite amongst patients in a displaced people's camp in Sudan.

BACKGROUND: Despite the importance of epidemiological studies in the development of effective control strategies and provision of basic health services for refugees and internally displaced persons (IDPs), data on the prevalence of malaria are limited. Thus, this study was conducted to estimate the molecular prevalence of malaria amongst the displaced population in Ardamata IDP camp in Al-Geneina City, Sudan. METHODS: A cross-sectional study was conducted from July 2018 to December 2018 to estimate malaria prevalence amongst the displaced population in Ardamata IDP camp in Al-Geneina City, Sudan. A total of 380 patients with suspected malaria were recruited. Nested polymerase chain reaction (nPCR) assays were performed to detect the Plasmodium genus and species. RESULTS: Of 380 patients, 232 (61.1%) were positive for malaria. Plasmodium falciparum was the only prevalent species detected amongst the study population. nPCR analysis revealed that none of the samples had Plasmodium vivax, Plasmodium ovale or Plasmodium malariae. The malaria prevalence rate was higher amongst males (67.1%) than in females (56.8%), and gender was the only risk factor that was significantly associated with malaria infection (p = .042). CONCLUSIONS: Despite control programmes, malaria remains a significant cause of illness amongst a displaced population. The high prevalence of malaria infection in this study indicates that additional health facilities and control strategies should be implemented in displaced camps and the surrounding areas.

Interleukin-10 (1082G/A) Polymorphism is Associated with Susceptibility of Acute Myeloid Leukemia Patients in Sudanese Population.

Background: Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenicfunctions and may have both tumor-promoting and -inhibiting properties. We examined the association between a single nucleotide polymorphism (SNP) in IL-10 -1082G/A (rs1800896) in Sudanese acute myeloid leukemia (AML) patients and to assess the association between polymorphisms in IL-10 -1082G/A (rs1800896) and the hematological profile in Sudanese patients with AML. Methods: A total of 30 patients with acute myeloid leukemia and 30 control subjects were enrolled in this study. Blood samples were collected from all patients in EDTA containing tubes. Genomic DNA was extracted from all blood samples using salting out method. The genotypic variants of IL-10 (-1082G/A) polymorphism were detected by allele specific-PCR. Results: We found that (36.7%) of patients have homogenous GG genotype, (43.3%) have heterogeneous GA genotype and (20.0%) have AA genotype. GA genotype was significantly associated with higher risk of AML compared with the homozygous Genotypes (GG and AA), there is no association between IL-10 (-1082G/A) polymorphism and AML sub-type, gender, age group, mean of hematological parameters. Conclusion: Our study concluded that GA genotype of IL-10 -1082G/A (rs1800896) polymorphism is a risk factor for AML and G allele is insignificantly higher than A allele in AML patient. No association between IL-10 (-1082G/A) polymorphism and AML sub-type, gender, age group, mean of hematological parameters.

Combined analysis of ZAP-70 and CD38 expression in sudanese patients with B-cell chronic lymphocytic leukemia.

OBJECTIVE: To investigate the ZAP-70 and CD38 expressions and their combined expressions in Sudanese B-CLL patients and their relationships with clinical and hematological characteristics as well as the disease staging at presentation. RESULTS: In the present cross-sectional descriptive study, analysis of ZAP-70 expression showed that 36/110 (32.7%) patients positively expressed ZAP-70 and insignificant higher presentation in intermediate and at advanced stages as well as no correlation was seen with hematological parameters and clinical features compared with negatively ZAP-70, on the other hand, 41/110 (37.3%) were CD38+ and no significant correlation was shown with the stage at presentation, clinical characteristics (except Splenomegaly, P = 0.02) and hematological parameters. However, in combined expressions of both ZAP-70 and CD38 together, 20/110 (18.2%) were concordantly ZAP-70+/CD38+, 53/110 (48.2%) concordantly ZAP-70-/CD38- and 37/110 (33.6%) either ZAP-70+ or CD38+, and these three groups showed insignificant correlation with clinical (except Splenomegaly, P = 0.03) and hematological parameters, and the stage at presentation. Our data showed the combined analysis of these two markers, lead to classify our patients into three subgroups (either concordant positive, negative or discordant expressions) with statistically insignificant correlation with clinical presentation (except Splenomegaly), hematological parameters and stage at presentation of B-CLL patients.

TP53 Gene 72 Arg/Pro (rs1042522) Single Nucleotide Polymorphism Contribute to Increase the Risk of B-Chronic Lymphocytic Leukemia in the Sudanese Population

Objective: This study aimed at exploring the association of TP53 72Arg/Pro polymorphism and Risk of Chronic Lymphocytic Leukemia and to assess the correlation between TP53 72Arg/Pro polymorphism and clinical parameter, hematological profile and some biological prognostic markers among Sudanese patients with chronic lymphocytic leukemia. Methods: A case-control study was conducted in Khartoum state, Sudan, during the period from April 2017 to April 2018, involved 110 B-CLL patients and 80 healthy volunteers as a control group. Physical examination, Complete Blood Count and Immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as Rai and Binet were studied. CD38 and ZAP70 were performed by Flow Cytometry. Blood samples were collected from all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit (Germany) and analyzed TP53 codon 72Arg/Pro Polymorphism by using AS-PCR. The statistical analysis was performed using SPSS version 23.0 software (Chicago, IL, USA). Results: the Arg/Pro was the most frequent genotype in B-CLL patients(50%), followed by Arg/Arg (25.5%) and Pro/Pro (24.5%), whereas in healthy control group Arg/Pro was the most frequent (47.5%), followed by Arg/Arg (45%) and Pro/Pro (7.5%). Our data indicate a higher frequency of homozygous Pro/ Pro in the B-CLL patients as compared to controls with an OR of 4.01 for the Pro/Pro genotype and lower frequency of Arg/Arg genotype in CLL patients as compared to controls with an OR of .42 for the Arg/Arg genotype. Also, the Pro allele showed higher risk than Arg allele (P value=0.000, OR 2.23, 95% CI=1.45-3.41). No significant association between gender, clinical staging systems (Rai, Binet), biological prognostic markers (CD38 expression or ZAP70 expression), and TP53 codon 72Arg/Pro polymorphisms, except Arg/Arg genotype tended to be associated with younger age (P =0.04). Conclusion: Our data suggested that Pro/Pro genotype contribute to increased susceptibility to B-Chronic Lymphocytic Leukemia risk in our population tenfold higher than those had Arg/Arg genotype.

Clinical presentation and hematological profile among young and old chronic lymphocytic leukemia patients in Sudan.

OBJECTIVE: To assess the clinical presentation and hematological profile among young (≤ 55 years) and old (> 55 years) chronic lymphocytic leukemia patients in Sudan. RESULT: In the present cross-sectional descriptive study, out of 110 cases studied, among them 31 (28.2%) were young (≤ 55 years) patients with mean age 48 years, and 79 (71.8%) were elder patients (> 55 years) with mean age 66 years, the overall mean age was 62.97 ± 12.06 with range (22-85 years), and 79 (71.8%) were males and 31 (28.2%) were females (M:F = 2.6:1) (P = 0.000). (7.3%) were asymptomatic, 61 (55.5%) presented with nonspecific complains. Generalized lymphadenopathy was seen in 52 (47.27%) with elder predominance (P = 0.03). Splenomegaly, hepatomegaly, thrombocytopenia and anemia were seen in 54 (49.1%), 14 (12.7%), 43 (39.1%) and 38 (34.5%) of patients respectively with male predominance. 54 (49.1%) and 42 (38.18%) of patients presented at Rai high risk and Binet C stages respectively with nearly same age and sex distribution. CLL in Sudan is a disease of elders, same as seen in literature, with high male to female ratio. In general hematological parameters means were noted to be distributed equally according to age and sex groups. Majority of patients were presented with nonspecific symptoms and nearly half of patients presented at late stages as reported in most developing countries.