Contribution of HLA class I (A, B, C) and HLA class II (DRB1, DQA1, DQB1) alleles and haplotypes in exploring ethnic origin of central Tunisians.

BACKGROUND: Estimation of HLA (Human leukocyte Antigen) alleles' frequencies in populations is essential to explore their ethnic origin. Anthropologic studies of central Tunisian population were rarely reported. Then, in this work, we aimed to explore the origin of central Tunisian population using HLA alleles and haplotypes frequencies. METHODS: HLA class I (A, B, C) and HLA class II (DRB1, DQA1, DQB1) loci genotyping of 272 healthy unrelated organ donors was performed by Polymerase Chain Reaction-Sequence Specific Oligonucleotide (PCR-SSO). We compared central Tunisians with other populations (Arabs, Berbers, Mediterraneans, Europeans, Africans, etc.) using alleles and haplotypes frequencies, genetic distances, Neighbour-Joining dendrogram and correspondence analysis. RESULTS: Among the 19 HLA A alleles, the 26 HLA B alleles, the 13 HLA C alleles, the 15 HLA DRB1 alleles, the 6 HLA DQA1 alleles and the 5 HLA DQB1 alleles identified in the studied population, HLA A*02 (22.8%), HLA B*50 (13.1%), HLA C*06 (21.8%), HLA DRB1*07 (17.8%), HLA DQA1*01 (32.1%) and HLA DQB1*03 (31.6%) were the most frequent alleles. The extended haplotypes HLA A*02-B*50-C*06-DRB1*07-DQA1*02-DQB1*02 (1.97%) was the most frequent HLA six-loci haplotype. CONCLUSION: Central Tunisians were very close to other Tunisian populations, to Iberians and North Africans. They were rather distant from sub-Saharan populations and eastern Mediterraneans especially Arabs although the strong cultural and religious impact of Arabs in this population.

Association between Human Leukocyte Antigen (HLA) DQB1*06 and HLA DQB1*03 and adverse outcomes in a group of critically ill patients with COVID-19 in Tunisia: a cross-sectional study.

Introduction: Human Leukocyte Antigen (HLA) system is a highly polymorphic genetic system associated with the prognosis of several infectious diseases. The aim of this study is to investigate the association of HLA polymorphism with the outcome of coronavirus disease 2019 (COVID-19) in Tunisian critically ill patients. Methods: this retrospective cross-sectional study included 42 consecutive patients hospitalized in intensive care unit (ICU) for COVID-19 in March 2021. Genotyping of HLA loci was performed by LABType™ sequence-specific oligonucleotide (SSO) typing kits (One lambda Inc, USA). Statistical analyses were performed using Statistical Package for Social Sciences (SPSS®) version 23.0. A p-value <0.05 was considered significant. Multivariable regression analysis was performed for the association between HLA polymorphism with adverse outcomes with adjustment for potential confounders such as age, sex, co-morbidities and blood type. Results: patients included in our study had a mean age of 64.5 ± 11.5 (34-83) years and were mainly men (64.3%; (n=27)). The most common cardiovascular risk factors were obesity (61.9%; (n=26)) and hypertension (26.2%; (n=11)). Thirty-two patients died (76.2%). Eleven patients (26.2%) required intubation during hospitalization. We found that HLA DQB1*06 allele was significantly associated with protection against mortality aOR: 0.066, 95% CI 0.005-0.821; p = 0.035. HLA DQB1*03 allele was significantly associated with protection against intubation aOR: 0.151, 95% CI 0.023-0.976; p = 0.047. Conclusion: it was found that there are 2 protective HLA alleles against COVID-19 severity and mortality in critically ill patients. This could allow focusing on people genetically predisposed to develop severe forms of COVID-19.

Assessment of antiphospholipid antibodies profiles based on severity of COVID-19 pneumonia.

Introduction: thrombotic events are the most severe complications of the coronavirus disease 2019 (COVID-19). It is known that anti-phospholipid antibodies (APL) could be involved in thrombosis mechanism. Thus, APL profiles were studied particularly in patients with severe and critical COVID-19, and their clinical impact. Methods: a retrospective study of 54 COVID-19 hospitalized patients (34 in intensive care unit (ICU) and 20 in non-ICU) was conducted. These COVID-19 patients were tested for the presence of LAC (lupus anticoagulant) using the ACLTOP750®, anti-cardiolipine (ACL) and anti-ß2glycoprotéine I (anti-ß2GPI) IgG/IgM/IgA by enzyme-linked immunosorbent assay (ELISA). IgA isotype was tested in only 25 patients. Results: anti-phospholipid antibodies were present in 74.1% of tested patients. LAC positivity was the highest (60.8%) among all patients, followed by IgM aCL (18.5%) and IgM anti-ß2GPI (14.8%). Besides, LAC and anti-ß2GPI IgA were the most predominant APL regarding the 25 patients tested for IgA isotype (52% and 24% respectively). Nine patients had thrombotic events, among them 6 were positive in APL and 5 were positive in LAC. However, there was any significant association between APL positivity or titers and thrombosis. There was also no significant difference between the two COVID-19 groups regarding APL profiles. Conclusion: given the relatively high frequency of APL and especially LAC, and given the multitude of thrombotic risk factors in these severely and critically ill COVID-19 patients, a prophylactic anticoagulation remains essential.

[Cytological and cytogenetic profile of 378 cases of acute myeloid leukemia in a Tunisian center].

INTRODUCTION: Acute leukemia (AL) represents the first hematological malignancy diagnosed and treated in Tunisia. OBJECTIVE: To describe the demographic, cytological, cytogenetic and prognostic characteristics of acute myeloid leukemia (AML) in the Tunisian center over a period of 11 years. METHODS: A retrospective study was performed on a series of AML cases diagnosed at Farhat Hached Hospital in Sousse, between January 2009 and December 2019. Cytological analysis according to the French-American-British classification and cytogenetic and molecular analysis allowed to classify AML according to the World Health Organization recommendations of 2016. The prognosis was established according to the recommendations of European Leukemia Net. RESULTS: The diagnosis of AML was confirmed in 378 cases with a median age at diagnosis of 43 years and a sex ratio of 1.32. AML with maturation was observed in 31% of cases. Recurrent abnormalities were detected in 25% of karyotypes, dominated by the t(15;17) translocation. The latter was associated with 75% of promyelocytic LA. Cytogenetic abnormalities associated with myelodysplasias were detected in 17% of cases, 59% of which had a complex karyotype. AMLs without specificity accounted for 57% of AMLs. Furthermore, 55% of patients had an intermediate prognosis. CONCLUSION: The lack of a Tunisian registry of hematological malignancies and the increasing incidence of AML, require epidemiological studies to establish the cytological and cytogenetic profile of the tunisian population. This will allow us to reinforce the diagnostic and therapeutic means with the ultimate goal of improving the survival of patients.

[Platelet satellitism during cutaneous leishmaniasis]. / Satellitisme plaquettaire au cours d'une leishmaniose cutanée.

Platelet satellitism is considered an uncommon phenomenon with an estimated frequency at 0.008%. About 100 cases have been published. If not recognized, this artifact can lead to an erroneous diagnosis of thrombocytopenia. We report the case of a patient, with cutaneous leishmaniasis, who developed an isolated thrombocytopenia. The blood smear prepared from peripheral blood sample collected with ethylenediaminetetraacetic acid showed platelets rosetting around polymorphonuclear. This phenomenon disappeared after treatment with Glucantime® for fifteen days and improvement of the lesions. We discuss also possible mechanisms to better understand this phenomenon.

Chediak-higashi syndrome presented as accelerated phase: case report and review of the literature.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease, characterized by partial oculocutaneous albinism, recurrent pyogenic infections (skin, mucosa and respiratory system), and neurologic deficit. The hallmark of this syndrome is the presence of abnormal intracytoplasmic giant granules in all granule containing cells including leukocytes in blood and bone marrow. A majority (85 %) of patients with CHS develop an accelerated phase consisting of a lymphoproliferative syndrome with hemophagocytosis and infiltration of most tissues. This phase is characterized by fever, jaundice, hepatosplenomegaly, lymphadenopathy, pancytopenia and neurological abnormalities. In this paper, we report a case of CHS presented as accelerated phase in a 9-month-old girl child.