Immunity in the Progeroid Model of Cockayne Syndrome: Biomarkers of Pathological Aging.

Cockayne syndrome (CS) is a rare autosomal recessive disorder that affects the DNA repair process. It is a progeroid syndrome predisposing patients to accelerated aging and to increased susceptibility to respiratory infections. Here, we studied the immune status of CS patients to determine potential biomarkers associated with pathological aging. CS patients, as well as elderly and young, healthy donors, were enrolled in this study. Complete blood counts for patients and donors were assessed, immune cell subsets were analyzed using flow cytometry, and candidate cytokines were analyzed via multi-analyte ELISArray kits. In CS patients, we noticed a high percentage of lymphocytes, an increased rate of intermediate and non-classical monocytes, and a high level of pro-inflammatory cytokine IL-8. In addition, we identified an increased rate of particular subtypes of T Lymphocyte CD8+ CD28- CD27-, which are senescent T cells. Thus, an inflammatory state was found in CS patients that is similar to that observed in the elderly donors and is associated with an immunosenescence status in both groups. This could explain the CS patients' increased susceptibility to infections, which is partly due to an aging-associated inflammation process.

Tunisian Newborn's Cord Blood: Reference Values of Complete Blood Count and Hemoglobin Fractions.

OBJECTIVE: This study was aimed to establish local reference values for hematological indices and hemoglobin (Hb) fractions in umbilical cord blood (UCB) for the northern population of Tunisia. STUDY DESIGN: Our study included full-term newborns by vaginal deliveries. Hematological parameters were collected using an automated blood cell counter. The amounts of Hb fractions were measured by capillary electrophoresis of Hb. Statistical analysis was performed using R software. RESULTS: A total of 328 cord blood samples were analyzed. Among them, 154 (male: 44.8%, female: 55.2%) were used to establish reference values. The normal reference values of complete blood count (CBC) and Hb fractions were calculated. Mean neonatal Hb was 14.75 ± 2.26 g/dL. Gestational age affects the expression of CBC values as red blood cell (RBC), Hb, hematocrit (Hct), mean corpuscular volume (MCV), white blood cell (WBC), and the Hb profile. Umbilical blood hemogram parameters and Hb profile are affected by the environment; higher in newborns from urban regions but not affected by gender ratio. CONCLUSION: Reference ranges of normal CBC indices and Hb fractions have been successfully established in Tunisian neonates' UCB. Our data suggest reference values that could be useful for neonatal patients' laboratory results and clinical interpretation. KEY POINTS: · Reference values for CBC and hemoglobin fractions have been established.. · Hematological reference for UCB is useful to identify hemolytic anemia cases early.. · UCB hematological values are influenced by gestational age and probably by environmental factors..

Biochemical, Cellular, and Proteomic Characterization of Hereditary Spherocytosis Among Tunisians.

BACKGROUND/AIMS: Hereditary Spherocytosis (HS) is the most common erythrocyte membrane disorder causing hemolytic anemia. The wide heterogeneity of both clinical and laboratory manifestations of HS contributes to difficulties associated with the diagnosis of this disorder. Although massive data previously reported worldwide, there is yet no data on HS among the Tunisian population. Here we aim to characterize HS in Tunisian patients at biochemical and cellular levels, identify the membrane protein deficiency, and compare the accuracy of the diagnostic tests to identify the most appropriate assay for HS diagnosis. METHODS: We investigated 81 patients with hemolytic anemia and 167 normal controls. The exploration of HS based on clinical and family history, physical examination, and the results of laboratory tests: blood smear, osmotic fragility test (OFT), cryohemolysis test (CT), pink test (PT), eosine-5'-maleimide (EMA) test, and erythrocyte membrane protein electrophoresis. RESULTS: We identified 21 patients with HS, classified as severe (6/21;28.5%), moderate (10/21;47.6%), and mild (5/21;23.8%). The most prevalent protein deficiency was the band 3 protein detected in ten Tunisian HS patients. The EMA test showed a high specificity (97.5%) and sensitivity (94.7%) for HS diagnosis compared to the other screening tests. Interestingly, fourteen among sixteen patients presenting with homozygous sickle cells HbSS showed an increase of EMA fluorescence intensity compared to other anemic patients. CONCLUSION: Our study highlights the efficiency of the EMA dye for the detection of HS whatever the nature of the involved protein deficiency. We report for the first time, the most prevalent protein deficiency among Tunisians with HS. Moreover, we found that the combination of the EMA-binding test with PT or incubated OFT improves the diagnosis sensitivity while maintaining a good specificity.

Antiphospholipid Antibodies and Procoagulant Profile in Tunisians With Inflammatory Bowel Diseases.

The hypercoagulable state accompanying inflammatory bowel diseases (IBDs) is still poorly understood. The aim of this study was to assess antiphospholipid antibodies (APAs) and a large panel of inherited and acquired thrombotic markers simultaneously in a sample of Tunisian patients with IBD. In total, 89 consecutive patients with IBD (mean age 38 ± 15 years; 48 with Crohn disease and 41 with ulcerative colitis) and 129 controls were prospectively evaluated for immunoglobulin (Ig) G, IgM, and IgA antibodies against cardiolipin (aCL), ß2glycoprotein I (aß2GPI), and prothrombin (aPT); IgG and IgM antibodies against phosphatidic acid (aPA), phosphatidylinositol (aPI), and annexin V (aAnnV); lupus anticoagulant (LA); coagulation factors; natural inhibitors; and thrombotic genetic polymorphisms. Levels of fibrinogen, factors II, V, and VIII and von Willebrand factor, antithrombin, and protein C were significantly higher in patients with IBD than in controls (P < .05 for all comparisons). At least 1 APA subset was detected in 54 patients. The frequencies of antibodies against anionic phospholipids-aCL, aPI, and aPA-in patients with IBD were 15.9%, 21.3%, and 14.6%, respectively. The frequencies of antiphospholipid cofactor antibodies were 39.8% for aß2GPI and 15.7% for both aAnnV and aPT. Isolated aß2GPI IgA was detected in 22 patients, and 12 (13.5%) patients had LA. The IgA aß2GPI antibodies were frequently detected in Tunisian patients with IBD. These results are of potential diagnostic, prognostic, and therapeutic interest.

Frequency of specific coagulation inhibitors and antiphospholipid antibodies in Tunisian haemophiliacs.

Production of factor VIII or factor IX inhibitors is a major complication limiting the efficiency of substitutive therapy in haemophiliacs. Moreover, viral infections, the second serious complication of replacement therapy, may be associated to the occurrence of antiphospholipid antibodies which paradoxically lead to thrombosis. We investigated the prevalence of coagulation inhibitors (factor VIII and factor IX inhibitors, antiphospholipid antibodies) in Tunisian haemophiliacs, and we assessed concomitant coagulation factor deficiencies. Thirty-two previously treated haemophiliacs (20 haemophiliacs A; 12 haemophiliacs B) were screened for factor VIII and factor IX inhibitors by APTT mixing study, Bethesda test and modified Nijmegen method, and investigated for the presence of anticardiolipin, anti-ß2 glycoprotein I, lupus anticoagulant and associated coagulation factors deficiencies. The frequency of factor VIII and factor IX inhibitors was low (5%) in contrast to the high prevalence of antiphospholipid antibodies (28.1%). Four and nine patients were positive for anticardiolipin and anti-ß2 glycoprotein I, respectively. No lupus anticoagulant was detected. The prevalence of antiphospholipid antibodies was higher in patients with positive hepatitis C virus infection serology as compared to patients with negative serology (41.6% vs. 20%). Concomitant factor VII and/or factor V deficiency was found in 10 patients. In conclusion, the occurrence of factor VIII and factor IX inhibitors is rare among Tunisian haemophiliacs. The clinical relevance of antiphospholipid antibodies requires further investigations. We emphasize the importance of screening for concomitant deficiencies in haemophiliacs when the clinical presentation is suggestive.

[Dysfibrinogenemia and thrombosis. A case report]. / Association dysfibrinogénémie et thrombose. A propos d'un cas.

BACKGROUND: Congenital dysfibrinogenemia is a functional disorder of the fibrinogen that represents a rare cause of thrombophilia. AIM: To report a Tunisian case of the association dysfibrinogenemia and thrombosis. CASE: A woman with inherited dysfibrinogenemia associated with mild tendency to bleeding experienced a deep vein thrombosis of the lower-extremity at 26 years of age and a fatal pulmonary embolism a few years later. Paradoxically coagulation function of fibrinogen was markedly altered in vitro with a significantly prolonged prothrombin time, activated partial thromboplastin time and thrombin time, a functional fibrinogen level that was undetected and a severely impaired fibrin polymerisation. The thromboembolic events in the patient could be related to dysfibrinogenemia since the main causes of thrombophilia were excluded. CONCLUSION: Although it is rare, this cause of thrombophilia must not be misdiagnosed, systematic measuring of prothrombin time, activated partial thromboplastin time and functional fibrinogen might be helpful.

A prospective study of the prevalence of heparin-induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis.

Heparin, which is used at high doses in hemodialysis patients, may induce antibodies favoring thromboembolic complications. We prospectively investigated the prevalence of heparin-induced platelet-reactive antibodies in a cohort of 38 pediatric hemodialysis patients, by means of heparin/platelet factor 4 (H/PF4) ELISA and heparin-induced platelet activation assay (HIPA). We also assessed other acquired and congenital hypercoagulable states. Heparin-induced antibodies were detected in 13 and 21% of patients with HIPA and ELISA, respectively. Anti-H/PF4 antibodies were negatively correlated with the number of hemodialysis sessions. These antibodies disappeared after a median time of 6 months despite continuing heparin treatment. The prevalence of antiphospholipid antibodies was 21% (anticardiolipin 10.5%, anti-beta2GPI 13%, and lupus anticoagulant 5%). Blood levels of homocysteine, factor VIII, and fibrinogen were significantly higher and factor II levels were significantly lower in hemodialysis patients than in controls, whereas factor VII, factor IX, and natural coagulation inhibitor levels were similar in patients and controls. Overall, 26 of 38 patients had at least one biomarker of hypercoagulability, but only 1 patient, without anti-H/PF4 antibodies, presented with thrombosis. In conclusion, heparin induces the transient production of anti-H/PF4 antibodies in children undergoing hemodialysis, but other abnormalities probably contribute to hypercoagulability. These findings may help to improve the diagnosis and management of thrombotic events in hemodialysis patients.

[Primary renal non-Hodgkin lymphoma]. / Lymphome non-Hodgkinien rénal primitif.

Primary renal non Hodgkin lymphoma is rare and unusual because the renal parenchyma does not have lymphatics. We report a case of bilateral primary lymphoblastic T lymphoma presenting with renal insufficiency in a 14 year old girl. We discuss clinical, pathological particularity and prognosis.