Elfishawi, M. M., F. Elgengehy, ghada Mossallam, S. elfishawi, M. Alfishawy, A. A. Gad, and I. Mokhtar, "HLA Class I in Egyptian patients with Behçet's disease: new association with susceptibility, protection, presentation and severity of manifestations.", Immunological investigations, vol. 48, issue 2, pp. 121-129, 2019. Abstract

INTRODUCTION: Behçet's disease is an autoimmune disease with diverse clinical manifestations with vasculitis being the hallmark of the disease. The aim of this work is to study the genetic association between human leukocyte antigen (HLA) class-I molecules of Egyptians with Behçet's disease and the disease susceptibility and clinical patterns.

METHODS: Fifty-seven patients diagnosed with Behçet's disease according to the 1990 International Study Group (ISG) criteria for Behçet's disease coming from Egyptian origin up to the third grandfather were included in the study. Healthy controls were taken from HLA Class-I case control studies in Egyptian population yielding a pool of 221 healthy controls. HLA Class-I typing for patients was done using Reverse Sequence specific oligonucleotide probes (rSSO).

RESULTS: Male patients represented 89% of the sample. Mean age of onset was 25.81 (± 6.7) years and mean disease duration was 9.47 (± 7.4) years. Behçet's disease was associated with HLA-A*24 and HLA-B*42 (p = 0.001) and highly associated with HLA-A*68 and B*15 and B*51 (p < 0.001). While HLA A*03 and B*52 were protective for Behçet's (p = 0.002 and 0.007). Interestingly, HLA-B*51 and HLA-A*68 (p = 0.005 and 0.023) were associated with the blinding eye disease. HLA-B*51 was protective from Neurological and vascular involvement (p = 0.005 and 0.032, respectively).

CONCLUSION: Behçet's disease is associated with HLA Class-I A*24, A*68 and B*15, B*42 and B*51 in Egyptian patients while A*03 and B*52 were found to be protective. Interestingly, HLA B*51 and A*68 could be considered as poor prognostic factor for eye involvement.

Rasekh, E. O., R. Osman, D. Ibraheem, Y. madney, E. Radwan, A. Gameel, A. Abdelhafiz, A. Kamel, and S. elfishawi, "Acute lymphoblastic leukemia-like treatment regimen provides better response in mixed phenotype acute leukemia: a comparative study between adults and pediatric MPAL patients.", Annals of hematology, 2020. Abstract

Mixed phenotype acute leukemia (MPAL) is a rare type of leukemia with a limited number of studies conducted to characterize its clinical spectrum and most importantly the best treatment modality. MPAL blasts show more than one phenotype either myeloid/monocytic with T- or B-lymphoid or extremely rare triple lineage associated phenotypic markers. This study aimed to characterize MPAL cases with special emphasis on comparing adult and pediatric age groups, exploring treatment regimens, and clinical outcome. Among 2571 acute leukemia patients, 102 MPAL cases fulfilling the 2008/2016 WHO diagnostic criteria of MPAL were recruited in the study. The incidence of MPAL was 4% of acute leukemia patients. Pediatric cases were 54 (53%) while adults were 48/102 (47%). Myeloid/B-lymphoid phenotype was found in 86/102 (84%), with BCR-ABL fusion gene transcript detected in 14/102(13.7%) patients. ALL-like treatment showed better response rates as compared with the myeloid based regimen (p = 0.001). MPAL behaves in a manner that resembles in clinical features, their lymphoid progenitor counterpart leukemias both in adults and pediatric patients with superior treatment response to ALL-like regimen, especially in adults.

Elfishawi, M., G. Mossallam, D. G. Augusto, G. Montero-Martin, H. de Bruin, L. Van de Pasch, P. J. Norman, E. Rozemuller, M. Fernandez-Vina, A. Abrudescu, et al., "Behçet disease, new insights in disease associations and manifestations: a next-generation sequencing study.", Clinical and experimental immunology, 2021. Abstract

Behçet disease is a multi-system disease associated with human leukocyte antigen (HLA) class I polymorphism. High-resolution next-generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behçet disease and 160 healthy geographic and ethnic-matched controls were genotyped for HLA class I loci (HLA-A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High-resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA-B*51:08 [odds ratio (OR) = 19·75, 95% confidence interval (CI) = 6·5-79; P < 0·0001], HLA-B*15:03 (OR = 12·15, 95% CI = 3·7-50·7; P < 0·0001), HLA-C*16:02 (OR = 6·53, 95% CI = 3-14; P < 0·0001), HLA-A*68:02 (OR = 3·14, 95% CI = 1·1-8·9; P < 0·01) were found to be associated with Behçet disease, as were HLA-DRB1*13:01 and HLA-DQB1*06:03 (OR = 3·39, 95% CI = 0·9-18·9; P = 0·04 for both). By contrast, HLA-A*03:01 (OR = 0·13, 95% CI = 0-0·8; P = 0·01) and HLA-DPB1*17:01 were found to be protective (OR = 0·27, 95% CI = 0·06-1·03; P = 0·02). We identified strong linkage disequilibrium between HLA-B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behçet disease. HLA-B*51:08 was significantly associated with legal blindness (OR = 2·98, 95% CI = 1·06-8·3; P = 0·01). In Egyptian Behçet patients, HLA-B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement.

Kamel, A. M., S. El-Fishawi, E. O. Rasekh, E. R. Radwan, A. Zeidan, A. El-Said, A. H. Zaky, M. Abdelfattah, Ahmed Refaat, MD, and R. Abdel Fattah, "Variability of contribution of vitamin D receptor gene polymorphisms to outcome of HLA-matched sibling allogeneic bone marrow transplantation", Leukemia & lymphoma, vol. 59, no. 12: Taylor & Francis, pp. 2963–2972, 2018. Abstract
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Misra, M. K., D. G. Augusto, G. M. Martin, N. Nemat-Gorgani, J. Sauter, J. A. Hofmann, J. A. Traherne, B. González-Quezada, C. Gorodezky, W. Bultitude, et al., "Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop", Human Immunology: Elsevier, 2018. Abstract
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Elfishawi, M. M., F. T. Elgengehy, G. I. Mossallam, S. M. Elfishawi, M. M. Alfishawy, and I. M. Metwally, AB0556 HLA Revisited in Egyptian Patients with Behçet9s Syndrome: New Associations of Hla Alleles with Susceptibility, Protection, Presentation and Severity of The Disaese, : BMJ Publishing Group Ltd, 2016. Abstract
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elfishawi, S., M. Fouda, and ghada Mossallam, "P210 KIR haplotype and genotype distribution in egyptian unrelated healthy donors", Human Immunology, vol. 78: Elsevier, pp. 212, 2017. Abstract
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Elfishawi, S. M., G. I. Mossallam, R. A. El-Fattah, A. El-Haddad, and A. M. Kamel, "The effect of killer cell immunoglobulin-like receptor genotype on outcome of hematopoietic stem cell transplantation from matched sibling.", Human immunology, vol. 78, issue 11-12, pp. 684-691, 2017 Nov. Abstract

The alloreactivity of natural killer (NK) cell after allogeneic hematopoietic stem cell transplantation (AHSCT) is regulated by the interaction between donor killer immunoglobulin-like receptors (KIRs) and recipient human leukocyte antigen (HLA)-class I molecules. The aim was to identify KIR genes, haplotypes and their HLA-class I ligands and to investigate their association with transplantation outcome. The study included 65 patient/donor pairs who received AHSCT from HLA-matched identical siblings. KIR genotyping was done for donors using reverse sequence specific oligonucleotide probes (rSSO) coupled with luminex technology, while HLA-C genotyping was performed in patients using rSSO strip assay. In multivariate analysis, KIR2DS4 was associated with significant reduced incidence of relapse (p = .002). A trend towards reduced incidence of relapse was also observed with more than two KIR B motifs (p = .09), whereas a significant increased relapse was associated with homozygous HLA-C2 ligand compared to combined C1/C2 and C1/C1 (p = .04). Activating KIR2DS3 was associated with rapid leukocyte engraftment (p = .02). While, KIR 2DL5 was associated with decreased CMV infection (p = .03) and better platelets engraftment (p = .05). KIR genes, haplotypes and HLA-C alleles have an impact on HSCT outcome. Better selection of donors with favorable KIR genotype can improve HLA-matched sibling HSCT outcome especially for AML patients.

elfishawi, S., R. M. Abdelfattah, A. Elhaddad, A. Kamel, and ghada Mossallam, The Effect of Killer Cell Immunoglobulin-like Receptor Genotype on Outcome of Hematopoietic Stem Cell Transplantation from a Matched Donor, , Cairo, Cairo, 2015.