BackgroundGenetic variants in TOLLIP and MUC5B influence innate immune signaling and mucosal defense and have been implicated in interstitial lung disease (ILD) susceptibility. However, data from Indian populations remain scarce. This study aimed to characterize single nucleotide polymorphisms (SNPs) in TOLLIP and MUC5B among patients with interstitial lung disease (ILD) and its subtypes. Additionally, it investigated the relationship between these genetic variants and inflammatory biomarkers, as well as the patterns of linkage disequilibrium (LD) in patients with ILD from Western India.MethodsThis cross-sectional study enrolled 200 patients with ILD and 104 healthy controls. Six SNPs, TOLLIP rs3750920, rs111521887, rs5743890, rs5743894, rs5743854, and MUC5B rs35705950, were genotyped using Sanger sequencing and PCR-RFLP. Serum cytokine levels (IL-1β, TNF-α, IFN-γ, and IL-6) were measured using a multiplex bead-based immunoassay. LD was assessed using Haploview software.ResultsConnective tissue disease-related ILD (CTD-ILD) was the most common subtype (45%). The TOLLIP rs3750920_T allele was significantly more frequent in idiopathic pulmonary fibrosis (IPF) than in controls (66.1% vs. 50.5%; p = 0.038). The TOLLIP rs111521887_G allele was more frequent in CTD-ILD than controls (18.4% vs. 7.4%; p = 0.002). The TOLLIP rs5743890_C allele was more frequent in controls than ILD (7.5% vs. 2.9%; p = 0.016). The TOLLIP rs5743894_C allele was more frequent in all patients with ILD than in controls (14.5% vs. 8.1%; p = 0.03), and specifically in the IPF subtype (19.2% vs. 8.1%; p = 0.01). The TOLLIP rs5743854_G allele was found to be more frequent in the idiopathic NSIP subtype as compared to controls (41.2% vs. 23.2%; p = 0.033). The MUC5B rs35705950_T allele was significantly more frequent in ILD than controls (19.6% vs. 5.8%; p = 0.0008). Among cytokines, IFN-γ was significantly elevated in TOLLIP rs5743854 C/C and MUC5B rs35705950 G/G homozygous genotypes in patients with ILD. Furthermore, LD analysis revealed no significant haplotype blocks in this population.ConclusionThis study provided the first population-specific data on TOLLIP and MUC5B genotypes in Indian patients with ILD, highlighting genotype-driven variation in IFN-γ and distinct allele-frequency patterns compared to Western cohorts. This study also indicated that one-third of the Indian patients with ILD, higher than the 6–7% from currently available Asian data, had genotypes that may benefit from NAC therapy.
INTRODUCTION:Bombay (Oh) blood group individuals are typically transfused with Bombay group red blood cells because transfusion with other blood groups can lead to life-threatening hemolysis. The mutations in the FUT1 gene prevent the expression of the H antigen on red blood cells. METHODS:A 35-year-old man presented with severe anemia (hemoglobin, 4.8 g/dL) and was transfused with 3 units of O RhD-positive packed red blood cells at an outside hospital without adverse reaction. One month later, his blood group at our center was revealed as O RhD positive with panagglutination in reverse grouping. Anti-H lectin was negative, and crossmatch with O RhD-positive units showed strong incompatibility, indicating Bombay phenotype. RESULTS:Molecular testing revealed FUT1 c.725T>G homozygosity and FUT2 deletion. Concurrent evaluation revealed plasma cell leukemia with extensive bone marrow infiltration, which may explain the transient immunosuppression and no hemolysis. Bombay-compatible units were procured through the Rare Donor Registry and transfused safely, allowing initiation of chemotherapy. DISCUSSION:This case highlights that the absence of a transfusion reaction cannot exclude a true Bombay phenotype, underscoring the importance of molecular confirmation. It also emphasizes the timely coordination with donors and rare donor registries, ensuring the availability of compatible blood for patients with rare blood types.
Sickle cell gene is common in various population groups in different parts of India. This makes sickle cell disease a common and clinically relevant symptomatic hemoglobinopathy in India. Clinical features of this disease are very variable. The current review with perspective was created by reviewing national and international literature. Literature search in PubMed and in Indian literature resources as well as the author’s own experience of this disease biology spanning over more than 35 years was used as the primary database. Sickle cell anemia, sickle cell disease, was used as the stem against the search terminologies such as Clinical heterogeneity, Population distribution in India, Molecular Mechanisms for severity, Mechanisms, and Blood transfusion. Original articles and review articles were given preference over individual case reports. There were many studies on the relative prevalence of the disease in different parts of the country. The disease in general was milder compared to the Afro-Caribbean form of the disease. The disease in Nagpur and adjoining areas was more severe than that in Gujarat and adjoining Maharashtra. The sickle cell disease in the north east tea garden workers was also milder as also the disease seen in the Nilgiri hills of Tamil Nadu and Waynad district of Kerala. The clinical features looked into for severity are painful crisis, chest syndrome, necrosis of femoral heads, and stroke. Little data are available on the perinatal complications of the disease. The frequency and severity of the disease with the above-mentioned clinical presentations were lower in milder forms of disease and presented in relatively older age groups. High fetal hemoglobin and a deletional variety of alpha thal-mutation was associated with milder forms of the disease. Nutritional deficiency, degree of anemia, and coinheritance of beta thalassemia gene tend to minimize the severity. Splenomegaly was very common and often HbS beta thalassemia is misdiagnosed as sickle cell anemia. There are many ways by which the clinical presentation of Sickle cell disease (SCD) is seen but broadly interplay of vaso occlusion and hemolysis in different degrees and in different anatomical locations determines the clinical features and presentation of the condition. High ambient temperature and bad weather conditions also contribute toward differential clinical presentation of the disease and obviously occupation also plays a role. Priapism, pedal ulcers, and ocular manifestations of SCD are rarely reported. There is general consensus that there is clinical heterogeneity in the presentation of sickle cell disease in India both within and across population groups due to genetic and environmental background of the population. However, there are huge gaps in clinical information in this disease in different areas of the country and there are needs to initiate a large-scale population study related to clinical heterogeneity of the disease and correlate these presentations with genetic and environmental as well as nutritional status of the population. Most of the clinical presentation papers are often from hospital data and surely present more severely affected population. Chronic cardiovascular, renal, pulmonary, and hepatic conditions in various groups and in different age groups are poorly recorded.
