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Background: Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the underlying reason for the onset of T1D is unknown, due to their effector and regulatory roles in immune responses, cytokines are essential in developing autoimmune disorders. Interleukin (IL)16 is an immunomodulatory cytokine implicated in several inflammatory and autoimmune diseases. Objective: This study was designed to examine the association of IL16 gene polymorphisms, rs11556218 T > G and rs4778889 T > C, with the risk of T1D in Egyptian children. Methods: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, we analyzed rs11556218 T > G and rs4778889 T > C polymorphisms of the IL16 gene in 100 T1D subjects and 93 controls. Results: Rs11556218 T > G polymorphism of the IL16 gene was not associated with the risk of developing T1D. Analysis of IL16 gene rs4778889 T > C showed that the TT genotype had a considerably higher risk of T1D than the TC genotype [OR = 2.195 (1.205–3.999)]. In comparison to patients with the C allele [OR = 0.6914 (0.38–1.2569)], patients with the T allele [OR = 1.45 (0.7956–2.6296)] were notably more likely to have T1D. A significant decrease was found in the frequency of GT (OR = 0.43, p =.03) and TC (OR = 0.32, p =.011) haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms in T1D patients compared with controls. Conclusion: IL16 gene rs4778889 T > C polymorphism might be associated with susceptibility to T1D. Egyptians with TT genotypes are more likely to develop T1D. However, GT and TC haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms highlight their protective role againstT1D disease. [ABSTRACT FROM AUTHOR]

Today there is increasing evidence concerning the association between individual genetic polymorphisms within proinflammatory cytokines and chronic hepatitis C (CHC) severity. It has been demonstrated that polymorphisms in some genes may significantly predict HCV infected patients' susceptibility to developing liver cirrhosis or their responsiveness to the treatment. We investigated the influence of single nucleotide polymorphisms (SNPs) in Interferon (IFN-γ) and Interferon Gamma-Inducible Protein 10 (IP-10) genes on cirrhosis risk in HCV-infected patients and their association with response to various direct-acting antiviral drugs (DAAs). IFN-γ (+874T/A, +2109A/G) and IP-10 (−135G/A, −1447A/G) genotypes were determined in 175 CHC Egyptian HCV patients (69 liver cirrhotic and 106 non-cirrhotic patients) using either single-stranded polymorphism polymerase chain reaction (SSP-PCR) or Restriction fragment length-PCR (RFLP-PCR) methods. IFN-γ + 874 TA, IP-10 − 135AA, and IP-10 − 1447AA and IP-10 − 1447GG genotypes are increased in patients developing liver cirrhosis compared to non-cirrhotic ones. Although, no statistical significance in their distribution was demonstrated, indicating the lack of association between these SNPs and liver cirrhosis susceptibility in HCV-infected patients. Haplotypes analysis between different loci on all selected genes showed a significant increase in AGGA and TAGA and a significant decrease in TGGA haplotypes in cirrhotic patients. Genotype frequencies at loci −135 and −1447 of IP-10 appeared to be in complete Linkage disequilibrium (LD) (D' = 0.999, r2 = 0.689). Our data support the concept that IFN-γ and IP-10 gene polymorphisms are not predictors of disease progression among Egyptian patients with HCV infection. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is a non-scarring hair loss of autoimmune etiology. The autoimmune regulator (AIRE) gene is believed to be an important driver in AA pathogenesis. Genetic variants can alter mRNA expression levels which may provoke an autoimmune response. A total of 337 males (97 AA patients and 240 controls) were enrolled in the current case–control study. On screening of the most frequent variants in the gene, rs2075876 (A/G) polymorphism in intron 5 was selected and genotyped using Real-Time PCR (polymerase chain reaction) technology. Additionally, circulatory AIRE expression levels were quantified by quantitative reverse-transcription PCR (qRT-PCR). Allelic discrimination analysis revealed GG genotype to be more frequent in patients (90.7% in AA compared to 32.5% in controls, p <.001). G variant conferred increased risk to alopecia under homozygote comparison (GG versus AA: OR = 16.1, 95%CI = 5.57–46.3), dominant model (GG+AG versus AA: OR = 7.24, 95%CI = 2.5–20.5), recessive model (GG versus AG+AA: OR = 20.3, 95%CI = 9.7–42.4), and allelic model (G versus A: OR = 11.6, 95%CI = 6.47–21.1). The expression levels of AIRE gene did not differ significantly between patients and controls and were not related to rs2075876 variant. In conclusion, the intronic variant (rs2075876) is suggested to be a potent susceptibility variant for AA development in the studied population. Abbreviations: AA: Alopecia areata; AIRE: Autoimmune Regulator; APECED: Autoimmune, Polyendocrinopathy Candidiasis Ectodermal Dystrophy; DLQI: Dermatology life quality index questionnaire; MIQE: Minimum information for publication of quantitative real-time PCR experiments; mTEC: Medullary thymic epithelial cells; PHD: Plant homeodomain; qRT-PCR: Quantitative reversetranscription-polymerase chain reaction; RA: Rheumatoid arthritis [ABSTRACT FROM AUTHOR]

Objective: Demonstration of rheumatoid arthritis (RA) characteristics in a large cohort of Egyptian patients. Methods: Retrospective analysis of data of 3219 RA patients attending the Rheumatology outpatient clinic, Kasr Alainy Hospital, Cairo University; from January 1995 till December 2015. Results: Mean age at disease onset was 36.1 ±13.4 years; 2774 (84%) were females and mean disease duration was 12.9 ±7.9 years. Regarding number of joint affected at disease onset; polyarticular pattern was found in 77.1%, pattern of joint involvement; combined small and large joints involvement was in 83.2%, subcutaneous nodules in 14.2%, interstitial lung disease in 0.3%, secondary Sjogren’s syndrome in 10.5%, hand bony erosions at diagnosis in 20.6%. Rheumatoid factor was positive in 52%. There was annual increase in the newly diagnosed cases (P = 0.017) reflecting increase in patients’ awareness and improvement of medical service, also annual increase in: mean age of onset (P < 0.001) reflecting changes in health measures, also in cases with monoarticular or oligoarticular patterns at disease onset (P = 0.02, 0.01 respectively) reflecting earlier diagnosis of patients and in patients with small joint involvement (P = 0.001) with a significant decline in: polyarticular pattern (P = 0.001), combined small and large joint affection (P < 0.001), and number of cases with hand bony erosions (P = 0.01) denoting earlier diagnosis, tight disease control. Conclusion: We found a female predominance, younger age at disease onset, lower frequency of extra articular manifestations, more frequent polyarticular pattern at disease onset and less erosive disease, denoting changing referral patterns, earlier diagnosis, improved disease control in Egyptian RA patients over 2 decades. Abbreviations: SNs: Subcutaneous nodules; 2ry SS: 2ry Sjogren’s syndrome; ILD: Interstitial lung disease; ACPA: Anti-cyclic citrullinated peptide antibodies; DMARDs: Disease modifying anti-rheumatic drugs. [ABSTRACT FROM AUTHOR]

Background: Non-Hodgkin lymphoma (NHL) is a major cancer in Egypt and worldwide and has many risk factors including genes involved in the immune response. Aim: we investigated the HLA-G 14bp gene polymorphism as a risk factor for NHL and its clinic pathologic features. The study involved 150 patients with NHL and 100 healthy control. Full histories, clinical examination, C.T scan and laboratory investigations such as CBC, LDH, ?2microglobulin and HCV RNA by qualitative real time PCR were performed for all subjects. HLA-G 14bp ins/del gene polymorphism was determined by PCR. Results: in our study, del/del, ins/del and dominant genotypes increased the risk of NHL by 11.01, 10.55 and 10.88 fold respectively (p<0.001) but the recessive genotype did not increase the risk of NHL (p=0.112). Cases with the del allele had a greater risk of NHL than those with the ins allele (p<0.001). del/del and ins/del genotypes were significantly associated with higher LDH and ?2microglobulin levels (p<0.001), lower Hb and platelet values (p<0.001), extra nodal sites (p=0.001), poor performance status (p=0.04) and relapse (p=0.001).  Conclusions:  the results suggest that HLA-G 14bp ins/del gene polymorphism is a risk factor for NHL in our Egyptian population and is associated with poor clinical pathological features. Abbreviations: Non-Hodgkin lymphoma (NHL), Diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Epstein-Barr virus (EBV), human T-cell lymphotropic/leukemia virus-1 (HTLV-1) [ABSTRACT FROM AUTHOR]

Aim of the work: This study aims to assess Growth differentiation factor-15 (GDF-15) level in Scleroderma patients and its relation to disease manifestations. Patients and methods: This study included 55 scleroderma patients and 40 age and sex matched healthy volunteers. All patients were subjected to full history taking, thorough clinical examination, and laboratory investigations. GDF-15 serum levels were analyzed in patients and controls using human GDF-15 immunoassay Quantikine ELISA kit. Results: The GDF-15 serum level was significantly higher in Systemic sclerosis (SSc) patients in comparison to healthy control individuals, p-value = 0.004. In addition, the GDF-15 serum levels increased in a significant way in patients with diffuse SSc than those with limited SSc, p = 0.026. Also, we had discovered a significant positive correlation between serum GDF-15 levels and the modified Rodnan score of the SSc patients, r = 0.442, p = 0.001 and a significant association was found between high GDF-15 level and SSc patients with interstitial pulmonary fibrosis (IPF) as compared to healthy controls (p = 0.002). However, no significant difference was found between SSc patients without IPF and healthy subjects regarding GDF-15 level (p = 0.106). Conclusion: GDF-15 serum levels were elevated in patients with SSc and correlated with the extent of skin fibrosis, and it was found to be higher in SSc patients with IPF. Such results may suggest a pivotal role of GDF-15 in fibrotic changes in SSc, and GDF-15 could be a treatment target in SSc patients in future. [ABSTRACT FROM PUBLISHER]

Background: Hepatocellular carcinoma has been recorded the commonest cancer in Egypt. This increasing incidence may be attributed to the high prevalence of hepatitis C virus with its complications, so this study aimed to investigate the association between the potentially functional polymorphisms of IL12A and IL12B genes as a risk factor of development of hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) infection in an Egyptian population. Materials and methods: We genotyped two loci of IL12 which were rs568408 (3'UTR G>A) for IL12A and rs3212227 (3'UTR A>C) for IL12B in 78 patients with HCC on top of chronic HCV infection. In addition, 64 cancer-free chronic HCV patients were studied, besides 92 healthy subjects who were included as control. Results: Study of rs568408 (G>A) gene polymorphism showed that the A allele is higher while the G allele is lower in HCC cases than cancerfree chronic HCV patients (p = 0.006*). The A-containing genotypes AG and (AG+AA) were higher while the GG was lower (p = 0.009* and p = 0.005*), respectively. The study of the rs3212227 (A>C) polymorphism showed neither statistically significant differences between the C and A allele (p = 0.2) nor between CC, AC, or AC+CC in HCC cases and cancer-free chronic HCV patients (p = 0.7, p = 0.2, and p = 0.29), respectively. Conclusion: Our findings showed that IL12A rs568408 (G>A) polymorphism may contribute to the risk of HCC on top of chronic HCV infection, whereas that of IL12B rs3212227 (A>C) do not. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease, with multiple genetic and environmental factors involved in its etiology. The toll-like receptor 9 (TLR9) gene has been reported to have important roles in the development and progression of SLE. In this case-control study, the effect of TLR9 polymorphism on susceptibility to SLE was investigated in Egyptian patients. Methods: We studied the distribution of the TLR9rs352139 (G+1174A)single nucleotide polymorphism (SNP) by allele-specific polymerase chain reaction (PCR) in 104 Egyptian patients with SLE and 108 age-, sex-, and ethnically matched controls. Results: There was no statistically significant difference in the distribution of theAAgenotype and alleles between SLE patients and the control group in our study; however, theGAheterozygous patients were three times more likely to develop SLE(P < 0.001). A significant association was detected between TLR9 genotypes and some of the disease manifestations as myositis (p= 0.032), psychosis (p= 0.014), photosensitivity (p= 0.002), and pleurisy (p= <0.001). Moreover, we observed a significant association between theTLR9 AAandGAgenotypes and the presence of antinuclear antibodies (ANA) (p= 0.038). Conclusion: TheG+1174ASNP in the toll receptor 9 gene may contribute to the genetic susceptibility of SLE in Egyptian patients. Also, an influence for this polymorphism on disease manifestations has been elucidated. [ABSTRACT FROM PUBLISHER]

Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin's lymphoma (NHL), this pilot study was designed to investigate the impact of CD38 (184C/G; rs6449182) and IL-6 (−174 G/C; rs1800795) gene polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma (DLBCL); major types of NHL. To the best of our knowledge, this study is the first one that examines CD38 polymorphism in the NHL. Genotyping polymorphism is performed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) for CD38 and Mutagenically separated PCR (MS-PCR) for IL-6 in 100 Egyptian NHL patients with DLBCL subtype and 119 normal controls. The serum level of IL-6 was measured using Enzyme-linked immunosorbent assay (ELISA). CD38 (184C/G) genotype is significantly increased in NHL patients ( p < 0.01), while the GG genotype is significantly increased in controls ( p < 0.05). Only two genotypes were found (GG and GC) in IL-6 (−174), no CC in our NHL patients and only one case in the controls. Insignificant change in IL-6 (−174 G/C) genotypes was recorded. Significantly increased serum IL-6 ( p < 0.05) was positively correlated ( r = 0.17; p < 0.05) with the disease. Taken together, our data stressed the importance of CD38 gene polymorphism in developing DLBCL. Our pilot study indicates that CD38 (184) CG genotype might play a role in DLBCL susceptibility in Egyptians. Additional prospective studies on larger population are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objective: To investigate the distribution of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) (++49 A/G) gene variants and the association of these variants with the clinical and laboratory findings in Egyptian children with Type-1 Diabetes (T1D). Methods: A case control study was done for 104 Egyptian children with T1D and 78 age and sex matched healthy control. CTLA-4 (++49 A/G) gene polymorphism typing was done by PCR amplification followed by restriction fragment length polymorphism (RFLP) method. Results: CTLA-4 G allele and GG homozygous genotype were significantly increased in T1D patients than in control group (P == 0.047, P == 0.048 respectively). There is no statistical difference between patient with optimal diabetic control (HbA1c < 8.5) and poor control (HbA1c ≥ 8.5) as regarding the CTLA-4 gene variant. The CTLA-4 GG genotype was statistically associated with younger age of patients (P == 0.027) and younger age of presentation (P == 0.036). Insignificant association was found between CTLA-4 alleles / genotypes and diabetic complications. Conclusion: The CTLA-4 ++49 GG homozygous genotype is associated with T1D in Egyptian children especially with younger age of onset and in younger patients, and not associated with grades of diabetic control or diabetic complication. [ABSTRACT FROM AUTHOR]

Objectives: To assess serum interleukin (IL) 13 levels in atopic diseases and to determine the role of IL-13R A1 gene polymorphism (++1398 A/G) in pathogenesis of these diseases. Methods: Serum total immunoglobulin (Ig) E and IL-13 levels were measured by ELISA and the IL-13R A1 gene (++1398 A/G) was screened by PCR-restriction fragment length polymorphism (RFLP) in 240 asthmatic children (120 atopic and 120 nonatopic) and 120 allergic rhinitis patients compared with 120 age-matched controls. Results: No significant association was observed between genotype frequencies of the IL-13R A1 ++1398 A/G polymorphism in patients groups compared to in controls. There was a significant increase in serum levels of total IgE & IL-13 towards heterozygous AG and homozygous GG than homozygous AA in atopic asthma, non-atopic asthma and allergic rhinitis groups (P < 0.001 for each). A highly significant increase of serum IL-13 in atopic asthma as compared with controls (P < 0.001) and with nonatopic asthmatics (P < 0.001) was shown. Conclusion: The IL-13R A1 ++1398 A/G polymorphism does not contribute to asthma or allergic rhinitis susceptibility, yet serum IL-13 can be used as a marker in atopic diseases and to differentiate between atopic and non-atopic asthma. [ABSTRACT FROM AUTHOR]