A case of iron deficiency anemia with co-existing Hb Fontainebleau.

Hb Fontainebleaue is a rare alpha chain variant in the Indian population which generates an unknown peak on hemoglobin HPLC study and does cause diagnostic difficulty to those who are not acquainted with this entity. We present a case of Hb Fontainebleau, an eighteen year old patient who presented with symptoms related to anemia to our department and unknown peak observed in HPLC plots lead us to family study and molecular characterization for this case

Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients

Systemic lupus erythematosus (SLE) is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1β were found to be significantly higher in SLE patients than healthy controls (P<0.001). Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL) was significantly higher (P=0.0430) than those of inactive disease patients (43.85±63.36 pg/mL). Mean level of TNF-α was 44.76±68.32 pg/mL for patients with active disease while it was 25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161). Similar results were obtained for IL-1β (P=0.0002). Correlation between IL-6, TNF-α, and IL-1β serum levels and SLEDAI score was observed (r=0.20, r=0.27, and r=0.38, resp.). This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease

Clinical, hematologic and molecular variability of sickle cell-\u3b2 thalassemia in western India

Background: Sickle cell-\u3b2 thalassemia (HbS-\u3b2 thalassemia) is a sickling disorder of varying severity, which results from compound heterozygosity for sickle cell trait and \u3b2 thalassemia trait. The present study was undertaken to determine the genetic factors responsible for the clinical variability of HbS-\u3b2 thalassemia patients from western India. Materials and Methods: Twenty-one HbS-\u3b2 thalassemia cases with variable clinical manifestations were investigated. The \u3b1 and \u3b2 globin gene clusters were studied by molecular analysis. Results: Thirteen patients showed milder clinical presentation as against eight patients who had severe clinical manifestations. Four \u3b2 thalassemia mutations were identified: IVS 1-5 (G\u2192C), codon 15 (G\u2192A), codon 30 (G\u2192C) and codon 8/9 (+G). \u3b1 thalassemia and XmnI polymorphism in homozygous condition (+/+) were found to be common among the milder cases. The \u3b2S chromosomes were linked to the typical Arab-Indian haplotype (#31). Framework (FW) linkage studies showed that four \u3b2 thalassemia mutations were associated with different \u3b2 globin gene frameworks. Linkage of codon 15 (G\u2192A) mutation to FW2 is being observed for the first time. Conclusion: The phenotypic expression of HbS-\u3b2 thalassemia is not uniformly mild and \u3b1 thalassemia and XmnI polymorphism in homozygous condition (+/+) are additional genetic factors modulating the severity of the disease in the Indian subcontinent

Neonatal Screening and the Clinical Outcome in Children with Sickle Cell Disease in Central India.

BACKGROUND:Sickle cell disease (SCD) is a major health burden in India. The objective of the study was to establish a neonatal screening program and to understand the clinical course of children with SCD in central India. METHODS AND FINDINGS:Pregnant mothers were screened for sickle hemoglobin using the solubility test. Babies were screened by high performance liquid chromatography if the mother was positive for sickle hemoglobin. The diagnosis was confirmed by molecular analysis. They received early prophylactic treatment and vaccination. Of 2134 newborns screened, 104 were sickle homozygous (SS), seven had sickle β-thalassemia (S-β thal) and 978 were sickle heterozygous (AS). The other hemoglobin abnormalities detected included HbS-δβ thalassemia-1, HbSD disease-2, HbE traits-5, β-thalassemia traits-4, alpha chain variants-3 and HbH disease-1.These babies were followed up regularly for hematological and clinical evaluation. Pain, severe anemia requiring blood transfusions and acute febrile illness were the major complications with 59.7, 45.1 and 42.6 cases per 100 person years. Fetal hemoglobin (HbF) levels were inversely associated with vaso-oclussive crisis (VOC) and severe anemia while presence of alpha thalassemia increased the rate of painful events and sepsis. Six early deaths occurred among the SS babies. CONCLUSION:A systematic follow up of this first newborn SCD cohort in central India showed that 47% of babies presented within 1 year of age. In spite of the presence of the Arab-Indian haplotype many babies had severe manifestations

Clinical events observed in SS,S-βthalassemia and HbSD newborns on follow up.

<p>The numbers in the figure indicates the number of episodes. VOC-Vasoocclusive crisis, AFI- Acute febrile illness, B.T.- Blood transfusions.</p

The Fc Receptor Polymorphisms and Expression of Neutrophil Activation Markers in Patients with Sickle Cell Disease from Western India

Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB) are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India. Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age 12±8.58 years) with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry. Results. The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074, P-0.0471, resp.). We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231), whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312). Conclusion. The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils